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Sample records for age-matched wky rats

  1. BRAIN ACONITASE ACTIVITY IN SPONTANEOUSLY HYPERTENSIVE (SHR) AND WISTAR-KYOTO (WKY) RATS.

    EPA Science Inventory

    Animal models of susceptibility are critical for human health risk assessment. Previous studies indicate that spontaneously hypertensive (SHR) rats are more sensitive than Wistar-Kyoto (WKY) rats to the cholinesterase (ChE) inhibitors such as carbaryl and chlorpyrifos. This diffe...

  2. CARDIOVASCULAR RESPONSES IN UNRESTRAINED WKY-RATS TO INHALED ULTRAFINE CARBON PARTICLES

    EPA Science Inventory

    Abstract
    This study provides evidence for adverse cardiac effects of inhaled ultrafine particles (UFPs) in healthy WKY rats. Short term exposure (24 h) with carbon UFPs (180 ?g?m ?) induced a moderate but significant heart rate increase of 18 bpm (4.8 %) in association with a ...

  3. Low ethanol intake prevents salt-induced hypertension in WKY rats.

    PubMed

    Vasdev, Sudesh; Gill, Vicki; Parai, Sushil; Gadag, Veeresh

    2006-07-01

    Low alcohol intake in humans lowers the risk of coronary heart disease and may lower blood pressure. In hypertension, insulin resistance with altered glucose metabolism leads to increased formation of aldehydes. We have shown that chronic low alcohol intake decreased systolic blood pressure (SBP) and tissue aldehyde conjugates in spontaneously hypertensive rats and demonstrated a strong link between elevated tissue aldehyde conjugates and hypertension in salt-induced hypertensive Wistar-Kyoto (WKY) rats. This study investigated the antihypertensive effect of chronic low alcohol consumption in high salt-treated WKY rats and its effect on tissue aldehyde conjugates, platelet cytosolic free calcium ([Ca2+]i, and renal vascular changes. Animals, aged 7 weeks, were divided into three groups of six animals each. The control group was given normal salt diet (0.7% NaCl) and regular drinking water; the high salt group was given a high salt diet (8% NaCl) and regular drinking water; the high salt + ethanol group was given a high salt diet and 0.25% ethanol in drinking water. After 10 weeks, SBP, platelet [Ca2+]i, and tissue aldehyde conjugates were significantly higher in rats in the high salt group as compared with controls. Animals on high salt diets also showed smooth muscle cell hyperplasia in the small arteries and arterioles of the kidney. Ethanol supplementation prevented the increase in SBP and platelet [Ca2+]i and aldehyde conjugates in liver and aorta. Kidney aldehyde conjugates and renal vascular changes were attenuated. These results suggest that chronic low ethanol intake prevents salt-induced hypertension and attenuates renal vascular changes in WKY rats by preventing an increase in tissue aldehyde conjugates and cytosolic [Ca2+]i. PMID:16685463

  4. Age-related changes in the renal dopaminergic system and expression of renal amino acid transporters in WKY and SHR rats.

    PubMed

    Pinto, Vanda; Amaral, João; Silva, Elisabete; Simão, Sónia; Cabral, José Miguel; Afonso, Joana; Serrão, Maria Paula; Gomes, Pedro; Pinho, Maria João; Soares-da-Silva, Patrício

    2011-01-01

    This study examined age-related changes in renal dopaminergic activity and expression of amino acid transporters potentially involved in renal tubular uptake of l-DOPA in Wistar Kyoto (WKY) and spontaneously hypertensive rats. Aging (from 13 to 91 weeks) was accompanied by increases in systolic blood pressure (SBP) in both WKY and SHR. The sum of urinary dopamine and DOPAC and the urinary dopamine/l-DOPA ratio were increased in aged SHR but not in aged WKY. The urinary dopamine/renal delivery of l-DOPA ratio was increased in both rat strains with aging. LAT2 abundance was increased in aged WKY and SHR. The expression of 4F2hc was markedly elevated in aged SHR but not in aged WKY. ASCT2 was upregulated in both aged WKY and SHR. Plasma aldosterone levels and urinary noradrenaline levels were increased in aged WKY and SHR though levels of both entities were more elevated in aged SHR. Activation of the renal dopaminergic system is more pronounced in aged SHR than in aged WKY and is associated with an upregulation of renal cortical ASCT2 in WKY and of LAT2/4F2hc and ASCT2 in SHR. This activation may be the consequence of a counter-regulatory mechanism for stimuli leading to sodium reabsorption. PMID:21699911

  5. Colony social stress differentially alters blood pressure and resistance-sized mesenteric artery reactivity in SHR/y and WKY male rats.

    PubMed

    Toot, Jonathan D; Reho, John J; Novak, Jacqueline; Dunphy, Gail; Ely, Daniel L; Ramirez, Rolando J

    2011-01-01

    Increased sympathetic nervous system (SNS) activity, testosterone, and spontaneously hypertensive rat Y chromosome (SHR Yc) play a role in a genetic model of hypertension. Male rats with the SHR Yc and Wistar-Kyoto (WKY) autosomes (denoted SHR/y) exhibit these characteristics when compared to rats with the WKY Yc and WKY autosomes (denoted WKY). We hypothesized that chronic social stress will increase blood pressure and SNS activity more in SHR/y males compared to WKY males, resulting in increased myogenic reactivity along with decreased vasoconstriction of small mesenteric arteries. SHR/y and WKY males were housed in strain- specific colonies (10 males with 10 females) or as controls (10 males). Systolic blood pressure (SBP) and blood samples were collected prior to termination. Second-order mesenteric arteries were studied using a pressure arteriograph in which myogenic reactivity and phenylephrine (PE) responsiveness were measured. SHR/y colony SBP, and circulating norepinephrine and testosterone concentrations were elevated compared to control and WKY colony males (p < 0.05). Mesenteric artery myogenic reactivity was increased in SHR/y colony males (p < 0.001). Mesenteric arteries from SHR/y colony males exhibited a significant decrease in PE-induced constriction. Colony social stress elevated both SNS activity and testosterone level which may be responsible for the increased mesenteric artery myogenic reactivity, and SBP as noted in SHR/y males. PMID:20666653

  6. Stress-Hyperresponsive WKY Rats Demonstrate Depressed Dorsal Raphe Neuronal Excitability and Dysregulated CRF-Mediated Responses

    PubMed Central

    Lemos, Julia C; Zhang, Guojun; Walsh, Teresa; Kirby, Lynn G; Akanwa, Adaure; Brooks-Kayal, Amy; Beck, Sheryl G

    2011-01-01

    Major depression is a debilitating psychiatric disease that may be precipitated by a dysregulation of stress neurocircuitry caused by chronic or severe stress exposure. Moreover, hyperresponsivity to stressors correlates with depressed mood and may contribute to the etiology of major depression. The serotonergic dorsal raphe nucleus (DRN) is an important site in the neurocircuitry underlying behavioral responses to stressors, and is tightly regulated, in part, by a combination of intrinsic cell properties, autoinhibition, and GABAergic synaptic transmission. The stress-related neurotransmitter corticotropin-releasing factor (CRF) modulates DRN neuronal excitability and subsequent 5-HT release in the forebrain. Wistar Kyoto (WKY) rats exhibit exaggerated behavioral responses to stressors, that is, stress hyperresponsivity, and are considered an animal model of depression. To better understand the neurobiological basis of the stress hyperresponsivity, we used a combination of mRNA analysis and whole-cell electrophysiological techniques to measure differences in intrinsic activity and receptor response, in 5-HT- and non-5-HT-containing neurons of the DRN in WKY rats compared with Sprague-Dawley controls. In the WKY rat, there was a decrease in the neuronal excitability of 5-HT neurons coupled with decreased TPH2 production. Additionally, we found that CRF did not increase GABAergic activity in 5-HT neurons as is normally seen in 5-HT neurons of Sprague-Dawley controls. The CRF modulation of 5-HT DRN neurotransmission at the single-cell level is selectively disrupted in the WKY animal model of depression and may be one of the cellular correlates underlying depression. PMID:21160465

  7. Common prefrontal cortical gene expression profiles between adolescent SHR/NCrl and WKY/NCrl rats which showed inattention behavior.

    PubMed

    dela Peña, Ike; Bang, Minji; Lee, Jinhee; de la Peña, June Bryan; Kim, Bung-Nyun; Han, Doug Hyun; Noh, Minsoo; Shin, Chan Young; Cheong, Jae Hoon

    2015-09-15

    Factor analyses of attention-deficit/hyperactivity (ADHD) symptoms divide the behavioral symptoms of ADHD into two separate domains, one reflecting inattention and the other, a combination of hyperactivity and impulsivity. Identifying domain-specific genetic risk variants may aid in the discovery of specific biological risk factors for ADHD. In contrast with data available on genes involved in hyperactivity and impulsivity, there is limited information on the genetic influences of inattention. Transcriptional profiling analysis in animal models of disorders may provide an important tool to identify genetic involvement in behavioral phenotypes. To explore some of the potential genetic underpinnings of ADHD inattention, we examined common differentially expressed genes (DEGs) in the prefrontal cortex of SHR/NCrl, the most validated animal model of ADHD and WKY/NCrl, animal model of ADHD-inattentive type. In contrast with Wistar rats, strain representing the "normal" heterogeneous population, SHR/NCrl and WKY/NCrl showed inattention behavior in the Y-maze task. The common DEGs in the PFC of SHR/NCrl and WKY/NCrl vs. Wistar rats are those involved in transcription (e.g. Creg1, Thrsp, Zeb2), synaptic transmission (e.g. Atp2b2, Syt12, Chrna5), neurological system process (e.g. Atg7, Cacnb4, Grin3a), and immune response (e.g. Atg7, Ip6k2, Mx2). qRT-PCR analyses validated expression patterns of genes representing the major functional gene families among the DEGs (Grin3a, Thrsp, Vof-16 and Zeb2). Although further studies are warranted, the present findings indicate novel genes associated with known functional pathways of relevance to ADHD which are assumed to play important roles in the etiology of ADHD-inattentive subtype. PMID:26048425

  8. Prematurely Delivered Rats Show Improved Motor Coordination During Sensory-evoked Motor Responses Compared to Age-matched Controls

    PubMed Central

    Roberto, Megan E.; Brumley, Michele R.

    2014-01-01

    The amount of postnatal experience for perinatal rats was manipulated by delivering pups one day early (postconception day 21; PC21) by cesarean delivery and comparing their motor behavior to age-matched controls on PC22 (the typical day of birth). On PC22, pups were tested on multiple measures of motor coordination: leg extension response (LER), facial wiping, contact righting, and fore- and hindlimb stepping. The LER and facial wiping provided measures of synchronous hind- and forelimb coordination, respectively, and were sensory-evoked. Contact righting also was sensory-evoked and provided a measure of axial coordination. Stepping provided a measure of alternated forelimb and hindlimb coordination and was induced with the serotonin receptor agonist quipazine. Pups that were delivered prematurely and spent an additional day in the postnatal environment showed more bilateral limb coordination during expression of the LER and facial wiping, as well as a more mature righting strategy, compared to controls. These findings suggest that experience around the time of birth shapes motor coordination and the expression of species-typical behavior in the developing rat. PMID:24680729

  9. ITI-Signals and Prelimbic Cortex Facilitate Avoidance Acquisition and Reduce Avoidance Latencies, Respectively, in Male WKY Rats

    PubMed Central

    Beck, Kevin D.; Jiao, Xilu; Smith, Ian M.; Myers, Catherine E.; Pang, Kevin C. H.; Servatius, Richard J.

    2014-01-01

    As a model of anxiety disorder vulnerability, male Wistar-Kyoto (WKY) rats acquire lever-press avoidance behavior more readily than outbred Sprague-Dawley rats, and their acquisition is enhanced by the presence of a discrete signal presented during the inter-trial intervals (ITIs), suggesting that it is perceived as a safety signal. A series of experiments were conducted to determine if this is the case. Additional experiments investigated if the avoidance facilitation relies upon processing through medial prefrontal cortex (mPFC). The results suggest that the ITI-signal facilitates acquisition during the early stages of the avoidance acquisition process, when the rats are initially acquiring escape behavior and then transitioning to avoidance behavior. Post-avoidance introduction of the visual ITI-signal into other associative learning tasks failed to confirm that the visual stimulus had acquired the properties of a conditioned inhibitor. Shortening the signal from the entirety of the 3 min ITI to only the first 5 s of the 3 min ITI slowed acquisition during the first four sessions, suggesting the flashing light (FL) is not functioning as a feedback signal. The prelimbic (PL) cortex showed greater activation during the period of training when the transition from escape responding to avoidance responding occurs. Only combined PL + infralimbic cortex lesions modestly slowed avoidance acquisition, but PL-cortex lesions slowed avoidance response latencies. Thus, the FL ITI-signal is not likely perceived as a safety signal nor is it serving as a feedback signal. The functional role of the PL-cortex appears to be to increase the drive toward responding to the threat of the warning signal. Hence, avoidance susceptibility displayed by male WKY rats may be driven, in part, both by external stimuli (ITI signal) as well as by enhanced threat recognition to the warning signal via the PL cortex. PMID:25484860

  10. Antidepressant-like effects of curcumin in WKY rat model of depression is associated with an increase in hippocampal BDNF

    PubMed Central

    Hurley, Laura L.; Akinfiresoye, Luli; Nwulia, Evaristus; Kamiya, Atsushi; Kulkarni, Amol; Tizabi, Yousef

    2012-01-01

    Curcumin is the principal active ingredient found in turmeric (Curcuma longa), a plant used in traditional Asian diets and herbal medicines. It is known to have a wide range of biological actions including antidepressant-like effects which have been observed in stress-induced depression models. This study was designed to investigate the antidepressant potential of curcumin in a non-induced model of depression. Moreover, since brain derived neurotrophic factor (BDNF) has been implicated in antidepressant effects of many drugs, we also evaluated the effects of curcumin on BDNF in the hippocampus. Adult male Wistar Kyoto (WKY) rats, a putative model of depression, were injected acutely or chronically (10 d) with 50, 100, and 200mg/kg curcumin. Open field locomotor activity (OFLA) and forced swim test (FST), a measure of helplessness, were measured 1 hour after acute and 18–20 hours after last chronic injection. Results showed a dose-dependent reduction of immobility in the FST by curcumin in both acute and chronic studies, without any significant effect on OFLA. The effect of higher chronic curcumin dose in FST was still evident a week later. Chronic curcumin also resulted in a dose-dependent increase in hippocampal BDNF. This data provides evidence for an antidepressant-like effect of curcumin, possibly through increased neurotrophic activity, in the WKY model of depression, and support the notion that curcumin may prove an effective and lasting natural antidepressant. PMID:23142609

  11. [Effect of bilateral common carotid artery ligation on prostaglandin levels (TXA2, PGI2) in spontaneously hypertensive rats (SHRSP, SHRSR) and normotensive rats (WKY)].

    PubMed

    Katayama, Y; Suzuki, S; Shimizu, J; Inamura, K; Sugimoto, S; Terashi, A

    1986-06-01

    Three different levels of global forebrain ischemia were induced in rats and their plasma levels of Thromboxane B2 (TXB2) and 6 Keto PGF1 alpha were determined to investigate the relation between severity of ischemia and eicosanoid production. Ischemia stimulates the activity of cellular lipase whose actions cause deacylation of brain phospholipids and release of free fatty acids. Arachidonic acid (A.A.) is one of the predominant fatty acids which is liberated in brain after ischemia. A.A. is the primary substrate for the synthesis of prostaglandins (PGs), Thromboxane A2 (TXA2) and Prostacyclin (PGI2), which play an important role in regulation of platelet aggregation and vasotonus. Thromboxane is a potent platelet aggregator and vasoconstrictor. On the other hand, PGI2 has the opposite nature. Therefore it can be considered that PGs and moreover, the balance of TXA2 and PGI2 may have an intimate relation to the development of cerebral ischemia. Three different levels of ischemia were produced by bilateral carotid artery ligation (BLCL) using three kinds of rats with different blood pressure ranges, namely, SHRSP (Stroke-prone spontaneously hypertensive rats), SHRSR (Stroke-resistant spontaneously hypertensive rats) and WKY (Wistar kyoto rats). It is known that higher pressure groups suffer severe ischemia by BLCL procedure. Hypertensive rats (SHRSP, SHRSR) were originally produced from WKY. The experimental animals used were about 300 gr and 16 weeks old male rats. The plasma and brain TXB2 and 6 Keto-PGF1 alpha, stable metabolites of TXA2 and PGI2 were measured by radioimmunoassay. The chronological changes of brain and plasma PGs levels after ischemia using SHRSR were also investigated.(ABSTRACT TRUNCATED AT 250 WORDS) PMID:3524627

  12. Differential cardiotoxicity in response to chronic doxorubicin treatment in male spontaneous hypertension-heart failure (SHHF), spontaneously hypertensive (SHR), and Wistar Kyoto (WKY) rats

    SciTech Connect

    Sharkey, Leslie C.; Radin, M. Judith; Heller, Lois; Rogers, Lynette K.; Tobias, Anthony; Matise, Ilze; Wang, Qi; Apple, Fred S.; McCune, Sylvia A.

    2013-11-15

    Life threatening complications from chemotherapy occur frequently in cancer survivors, however little is known about genetic risk factors. We treated male normotensive rats (WKY) and strains with hypertension (SHR) and hypertension with cardiomyopathy (SHHF) with 8 weekly doses of doxorubicin (DOX) followed by 12 weeks of observation to test the hypothesis that genetic cardiovascular disease would worsen delayed cardiotoxicity. Compared with WKY, SHR demonstrated weight loss, decreased systolic blood pressure, increased kidney weights, greater cardiac and renal histopathologic lesions and greater mortality. SHHF showed growth restriction, increased kidney weights and renal histopathology but no effect on systolic blood pressure or mortality. SHHF had less severe cardiac lesions than SHR. We evaluated cardiac soluble epoxide hydrolase (sEH) content and arachidonic acid metabolites after acute DOX exposure as potential mediators of genetic risk. Before DOX, SHHF and SHR had significantly greater cardiac sEH and decreased epoxyeicosatrienoic acid (EET) (4 of 4 isomers in SHHF and 2 of 4 isomers in SHR) than WKY. After DOX, sEH was unchanged in all strains, but SHHF and SHR rats increased EETs to a level similar to WKY. Leukotriene D4 increased after treatment in SHR. Genetic predisposition to heart failure superimposed on genetic hypertension failed to generate greater toxicity compared with hypertension alone. The relative resistance of DOX-treated SHHF males to the cardiotoxic effects of DOX in the delayed phase despite progression of genetic disease was unexpected and a key finding. Strain differences in arachidonic acid metabolism may contribute to variation in response to DOX toxicity. - Highlights: • Late doxorubicin toxicity evaluated in normal, hypertensive, and cardiomyopathic rats. • Hypertension enhances the delayed toxicity of doxorubicin. • Genetic predisposition to cardiomyopathy did not further enhance toxicity. • Epoxyeicosatrienoic acids

  13. EFFECTS OF CARBARYL ON THE MOTOR ACTIVITY OF SPONTANEOUSLY HYPERTENSIVE (SHR) AND NORMOTENSIVE (WKY) RATS.

    EPA Science Inventory

    SHR rats have been widely used to investigate the etiology and mechanisms of hypertension. Recent evidence suggests SHR rats have an increased sensitivity to cholinesterase inhibitors. In an effort to develop animal models of susceptibility for use in risk assessment, this ex...

  14. Effects of subacute treatment with cocaine on activities of n-demethylase, UDP-glucuronyltransferase and sulfotransferase in WKY and SHR rat liver - sex and strain differences

    SciTech Connect

    Watanabe, H.K.; Hoskins, B.; Ho, I.K.

    1988-01-01

    The effects of subacute treatment with cocaine on activities of cocaine N-demethylase, UDP-glucuronyltransferase (GT) toward 4-nitrophenol and phenolphthalein and sulfotransferase (ST) toward androsterone and 4-nitrophenol in livers from Wistar Kyoto rats (WKY) and spontaneously hypertensive rats (SHR) were investigated. Hepatic metabolism of cocaine was different between the sexes (with males having higher N-demethylase activity) and the strains (with WKY rats having higher activity). The effects of subacute cocaine administration on the activity of cocaine N-demethylase were also sex- and strain-related. Whereas cocaine administration increased activity of hepatic N-demethylase in both female strains, it decreased activity in male WKY and had no effect on activity in male SHR. Sex and strain-related as well as cocaine-induced differences were also found in activities of hepatic GT toward 4-nitrophenol and phenolphtalein as well as in activity of hepatic ST towards andersterone and 4-nitrophenol. These results suggest that some of the individual variation in the effects of cocaine may be due to sex and genetic differences in the hepatic metabolism of cocaine and/or in sexually and/or genetically-determined differences in how cocaine affects hepatic metabolism of other xenobiotics. 20 references, 4 figures.

  15. Dietary phytosterols and phytostanols decrease cholesterol levels but increase blood pressure in WKY inbred rats in the absence of salt-loading

    PubMed Central

    2010-01-01

    Background There are safety concerns regarding widespread consumption of phytosterol and phytostanol supplemented food products. The aim of this study was to determine, in the absence of excess dietary salt, the individual effects of excess accumulation of dietary phytosterols and phytostanols on blood pressure in Wistar Kyoto (WKY) inbred rats that have a mutation in the Abcg5 gene and thus over absorb phytosterols and phytostanols. Methods Thirty 35-day old male WKY inbred rats (10/group) were fed a control diet or a diet containing phytosterols or phytostanols (2.0 g/kg diet) for 5 weeks. The sterol composition of the diets, plasma and tissues were analysed by gas chromatography. Blood pressure was measured by the tail cuff method. mRNA levels of several renal blood pressure regulatory genes were measured by real-time quantitative PCR. Results Compared to the control diet, the phytosterol diet resulted in 3- to 4-fold increases in the levels of phytosterols in plasma, red blood cells, liver, aorta and kidney of WKY inbred rats (P < 0.05). The phytostanol diet dramatically increased (> 9-fold) the levels of phytostanols in plasma, red blood cells, liver, aorta and kidney of these rats (P < 0.05). The phytosterol diet decreased cholesterol levels by 40%, 31%, and 19% in liver, aorta and kidney, respectively (P < 0.05). The phytostanol diet decreased cholesterol levels by 15%, 16%, 20% and 14% in plasma, liver, aorta and kidney, respectively (P < 0.05). The phytostanol diet also decreased phytosterol levels by 29% to 54% in plasma and tissues (P < 0.05). Both the phytosterol and phytostanol diets produced significant decreases in the ratios of cholesterol to phytosterols and phytostanols in plasma, red blood cells, liver, aorta and kidney. Rats that consumed the phytosterol or phytostanol diets displayed significant increases in systolic and diastolic blood pressure compared to rats that consumed the control diet (P < 0.05). The phytosterol diet increased renal

  16. Delivery of sry1, but not sry2, to the kidney increases blood pressure and sns indices in normotensive wky rats

    PubMed Central

    Ely, Daniel; Milsted, Amy; Dunphy, Gail; Boehme, Shannon; Dunmire, Jeff; Hart, Mike; Toot, Jonathon; Martins, Almir; Turner, Monte

    2009-01-01

    Background Our laboratory has shown that a locus on the SHR Y chromosome increases blood pressure (BP) in the SHR rat and in WKY rats with the SHR Y chromosome (SHR/y rat). A candidate for this Y chromosome hypertension locus is Sry, a gene that encodes a transcription factor responsible for testes determination. The SHR Y chromosome has six divergent Sry loci. The following study examined if exogenous Sry1 or Sry2 delivered to the kidney would elevate renal tyrosine hydroxylase, renal catecholamines, plasma catecholamines and telemetered BP over a 28 day period. We delivered 50 μg of either the expression construct Sry1/pcDNA 3.1, Sry2/pcDNA 3.1, or control vector into the medulla of the left kidney of normotensive WKY rats by electroporation. Weekly air stress was performed to determine BP responsiveness. Separate groups of animals were tested for renal function and plasma hormone patterns and pharmacological intervention using alpha adrenergic receptor blockade. Pre-surgery baseline and weekly blood samples were taken from Sry1 electroporated and control vector males for plasma renin, aldosterone, and corticosterone. BP was measured by telemetry and tyrosine hydroxylase and catecholamines by HPLC with electrochemical detection. Results In the animals receiving the Sry1 plasmid there were significant increases after 21 days in resting plasma norepinephrine (NE, 27%) and renal tyrosine hydroxylase content (41%, p < .05) compared to controls. BP was higher in animals electroporated with Sry1 (143 mmHg, p < .05) compared to controls (125 mmHg) between 2–4 weeks. Also the pressor response to air stress was significantly elevated in males electroporated with Sry1 (41 mmHg) compared to controls (28 mmHg, p < .001). Sry2 did not elevate BP or SNS indices and further tests were not done. The hormone profiles for plasma renin, aldosterone, and corticosterone between electroporated Sry1 and control vector males showed no significant differences over the 28 day period

  17. Glutathione system in young spontaneously hypertensive rats.

    PubMed

    Lee, S K; Arunkumar, Sundaram; Sirajudeen, K N S; Singh, H J

    2010-12-01

    Glutathione (GSH) forms a part of the antioxidant system that plays a vital role in preventing oxidative stress, and an imbalance in the oxidant/antioxidant system has been linked to the pathogenesis of hypertension. The aim of this study was to investigate the status of the GSH system in the kidney of spontaneously hypertensive rats (SHR). Components of the GSH system, including glutathione peroxidase (GPx), glutathione reductase (GR), glutathione-S-transferase (GST), and total GSH content, were measured in the kidneys of 4, 6, 8, 12, and 16 weeks old SHR and Wistar-Kyoto (WKY) rats. Systolic blood pressure of SHR was significantly higher from the age of 6 weeks onwards compared with age-matched WKY rats. GPx activity in the SHR was significantly lower from the age of 8 weeks onwards when compared to that in age-matched WKY rats. No significant differences were evident in the GPx-1 protein abundance, and its relative mRNA levels, GR, GST activity, and total GSH content between SHR and age-matched WKY rats. The lower GPx activity suggests of an impairment of the GSH system in the SHR, which might be due to an abnormality in its protein rather than non-availability of a cofactor. Its role in the development of hypertension in SHR however remains unclear. PMID:20680541

  18. Dissociation between spontaneously hypertensive (SHR) andWistar–Kyoto (WKY) rats in baseline performance and methylphenidate response on measures of attention, impulsivity and hyperactivity in a Visual Stimulus Position Discrimination Task

    SciTech Connect

    Thanos, P.K.

    2009-10-08

    The spontaneously hypertensive rat (SHR) is a widely accepted rodent model of Attention Deficit/Hyperactivity Disorder (ADHD), and methylphenidate (MP) is a central nervous systemstimulant that has been shown to have a dose-related positive effect on attention task performance in humans with ADHD. The current study was undertaken to compare SHR to its typical control strain, Wistar-Kyoto(WKY) rats, on the performance of a Visual Stimulus Position Discrimination Task (VSPDT) as well as of the responsiveness of the two rat strains to MP treatment. The rats were initially trained on the VSPDT, in which a light cue was presented randomly at three different cue-light intervals (1 s, 300 ms and 100 ms) over one of two levers, and presses on the lever corresponding to the light cue were reinforced with a food pellet. Once rats reached stable performance, the treatment phase of the study began, during which they received daily intraperitoneal (IP) injections of saline, 2 mg/kg, 5 mg/kg, and 10 mg/kg of MP in a randomized order immediately prior to being tested on the VSPDT. Baseline performance accuracy on the VSPDT did not differ between the groups. Furthermore, a striking strain dissociation was evident in the response of the two strains to treatment; VSPDT performance was substantially disrupted by the 5 and 10 mg/kg dose in the WKY rats but only mildly in the SHR rats. Response omissions were also increased only in WKY rats. Finally, both strains had increased locomotor activity in the operant chamber following MP treatment. These findings point to an important difference in response tendency toMP in the two strains that supports a view that a critical difference between these strains may suggest neurochemical and neuroadaptive differences associated with the behavioral impairments of ADHD.

  19. Sex-Steroid Regulation of Relaxin Receptor Isoforms (RXFP1 & RXFP2) Expression in the Patellar Tendon and Lateral Collateral Ligament of Female WKY Rats

    PubMed Central

    Dehghan, Firouzeh; Muniandy, Sekaran; Yusof, Ashril; Salleh, Naguib

    2014-01-01

    The incidence of non-contact knee injury was found higher in female than in male and is related to the phases of the menstrual cycle. This raised the possibility that female sex-steroids are involved in the mechanism underlying this injury via affecting the expression of the receptors for relaxin, a peptide hormone known to modulate ligament laxity. Therefore, this study aims to investigate the effect of sex-steroids on relaxin receptor isoforms (RXFP1 & RXFP2) expression in the ligaments and tendons of the knee. Methods: Ovariectomized adult female WKY rats were treated with different doses of estrogen (0.2, 2, 20 μg/kg), progesterone (4mg) and testosterone (125 & 250μg/kg) for three consecutive days. At the end of the treatment, the animals were sacrificed and the patellar tendon and lateral collateral ligament were harvested for mRNA and protein expression analyses by Real Time PCR and Western blotting respectively. Results: RXFP1, the main isoform expressed in these knee structures and RXFP2 showed a dose-dependent increase in expression with estrogen. Progesterone treatment resulted in an increase while testosterone caused a dose-dependent decrease in the mRNA and protein expression of both relaxin receptor isoforms. Discussion: Progesterone and high dose estrogen up-regulate while testosterone down-regulates RXFP1 and RXFP2 expression in the patellar tendon and lateral collateral ligament of rat's knee. Conclusion: Relaxin receptor isoforms up-regulation by progesterone and high dose estrogen could provide the basis for the reported increase in knee laxity while down-regulation of these receptor isoforms by testosterone could explain low incidence of non-contact knee injury in male. PMID:24465164

  20. DIFFERENTIAL EFFECTS OF CARBARYL IN BRAIN ACONITASE ACTIVITY IN SPONTANEOUSLY HYPERTENSIVE (SHR) AND WISTAR-KYOTO (WKY) RATS.

    EPA Science Inventory

    Animal models of susceptibility are crucial for quantitative human health risk assessment. Spontaneously hypertensive rats (SHR) have long been used in studies on the etiology and mechanisms of hypertension and are known to be prone to oxidative stress. Previous studies indica...

  1. Therapeutic effects and mechanism of conditioned media from human mesenchymal stem cells on anti-GBM glomerulonephritis in WKY rats.

    PubMed

    Iseri, Ken; Iyoda, Masayuki; Ohtaki, Hirokazu; Matsumoto, Kei; Wada, Yukihiro; Suzuki, Taihei; Yamamoto, Yasutaka; Saito, Tomohiro; Hihara, Kei; Tachibana, Shohei; Honda, Kazuho; Shibata, Takanori

    2016-06-01

    Recent studies have demonstrated that conditioned media derived from mesenchymal stem cells (MSC-CM) have therapeutic effects in various experimental diseases. However, the therapeutic mechanism is not fully understood. In the present study, we investigated the therapeutic effects and mechanism of MSC-CM in experimental antiglomerular basement membrane glomerulonephritis. We administered either MSC-CM or vehicle from day 0 to day 10 after the induction of nephrotoxic serum nephritis in Wistar-Kyoto rats. In vitro, we analyzed the effects of MSC-CM on TNF-α-mediated cytokine production in cultured normal human mesangial cells, proximal tubular (HK-2) cells, human umbilical vein endothelial cells, and monocytes (THP-1 and peripheral blood mononuclear cells). Compared with vehicle treatment, MSC-CM treatment improved proteinuria and renal dysfunction. Histologically, MSC-CM-treated rats had reduced crescent formation and glomerular ED1(+) macrophage infiltration and increased glomerular ED2(+) macrophage infiltration. Increased serum monocyte chemoattractant protein (MCP)-1 levels were observed in MSC-CM-treated rats. Renal cortical mRNA expression levels of proinflammatory cytokines, such as TNF-α and IL-6, and of the T helper cell 1 cytokine interferon-γ were greatly decreased by MSC-CM treatment. In vitro, pretreatment with MSC-CM blocked TNF-α-mediated IL-8 release in normal human mesangial cells and HK-2 cells. TNF-α-mediated MCP-1 release was enhanced by pretreatment with MSC-CM in human umbilical vein endothelial cells and HK-2 cells and was strikingly enhanced in THP-1 cells. Stimulation of peripheral blood mononuclear cells with a combination of MCP-1 and IL-4 enhanced the expression of M2-associated genes compared with IL-4 alone. We demonstrated that MSC-CM had therapeutic effects in experimental antiglomerular basement membrane glomerulonephritis that were mediated through anti-inflammatory effects that were partly due to acceleration of M2 macrophage

  2. Effect of sodium depletion on the release of /sup 3/Hnorepinephrine from central and peripheral tissue of Wistar-Kyoto and spontaneously hypertensive rats

    SciTech Connect

    Meldrum, M.J.; Xue, C.S.; Badino, L.; Westfall, T.C.

    1985-01-01

    To study the relationship between sodium intake, the sympathetic nervous system, and hypertension, a study was made of the effects of a 7-9 day dietary restriction of sodium in three different ages of spontaneously hypertensive rats (SHR) and Wistar-Kyoto rats (WKY). Field-stimulated (/sup 3/H)norepinephrine ( (/sup 3/H)NE) release was measured in portal vein, anterior hypothalamus, and the A2 region of the nucleus tractus solitarius (NTS) of 5- to 6-, 10- to 11-, and 28- to 30- week-old SHR and age-matched WKY. A low-sodium diet (0.05% Na+, control 0.5% Na+) significantly lowered stimulated (/sup 3/H)NE release from portal vein and anterior hypothalamus in SHR and WKY at all three ages. However, release from the A2 region was not altered by sodium restriction. The results of the present study suggest that lowered dietary sodium can selectively alter norepinephrine release in both the peripheral and central sympathetic nervous system of SHR and WKY. The results also suggest that the SHR at 5-6 weeks are more sensitive to altered dietary sodium than are age-matched WKY.

  3. Norepinephrine release and reuptake by hypothalamic synaptosomes of spontaneously hypertensive rats

    SciTech Connect

    Hano, T.; Jeng, Y.; Rho, J.

    1989-03-01

    We compared the overflow of endogenous norepinephrine during electrical field stimulation, the norepinephrine content, and the rate of initial neuronal uptake of (3H)norepinephrine in synaptosomes isolated from hypothalamus and brainstem of spontaneously hypertensive rats (SHR) and Wistar-Kyoto (WKY) rats at 7 and 13 weeks of age. The synaptosomes of two rats, a SHR and a WKY rat control, were simultaneously processed and subjected to the same electrical field stimulation. The overflow of endogenous norepinephrine during electrical stimulation (2 Hz, 2 minutes) in the hypothalamic synaptosomes of 7-week-old SHR was significantly greater, whereas the overflow of 13-week-old SHR was equivalent to the age-matched WKY rat. The norepinephrine content of synaptosomes was about the same in SHR and age-matched controls. There was also significantly enhanced (3H)norepinephrine uptake in the hypothalamic synaptosomes of young SHR, but neither the hypothalamic nor the brainstem samples of 13-week-old SHR showed any significant difference in their rate of (3H)norepinephrine uptake. These data are similar to those we observed (unpublished observations) in perfused mesenteric artery system in which norepinephrine release was significantly elevated during periarterial nerve stimulation only in young SHR. Thus, these results suggest that a parallel enhancement of norepinephrine release in hypothalamus with that of peripheral nervous system may play an important role during development of hypertension in young SHR.

  4. Chronic treatment with epigallocatechin gallate reduces motor hyperactivity and affects in vitro tested intestinal motility of spontaneously hypertensive rats

    PubMed Central

    Potenza, Maria Assunta; Montagnani, Monica; Nacci, Carmela; De Salvia, Maria Antonietta

    2016-01-01

    Background Green tea catechins seem to contribute toward reducing body weight and fat. Objective We aimed to investigate whether chronic administration of (–)-epigallocatechin-3-gallate (EGCG), the most abundant catechin of green tea, reduces weight gain in spontaneously hypertensive rats (SHR), an animal model of metabolic syndrome, by increasing motor activity and/or by altering gastrointestinal motility. Design Nine-week-old SHR were randomly assigned to two groups and treated by gavage for 3 weeks with vehicle dimethyl sulfoxide or EGCG (200 mg/kg/day). Age-matched Wistar-Kyoto (WKY) control rats were treated with vehicle alone. The effect of chronic administration of EGCG was evaluated on open-field motor activity and on ex vivo colonic and duodenal motility. Moreover, in vitro acute effect of 20-min incubation with EGCG (100 µM) or vehicle was evaluated in colonic and duodenal specimens from untreated WKY rats and SHR. Results Vehicle-treated SHR were normoglycemic and hyperinsulinemic, and showed a reduction of plasma adiponectin when compared to vehicle-treated WKY rats. In addition, consistent with fasting glucose and insulin values, vehicle-treated SHR were more insulin resistant than age-matched vehicle-treated WKY rats. Chronic treatment for 3 weeks with EGCG improved insulin sensitivity, raised plasma adiponectin levels, and reduced food intake and weight gain in SHR. Vehicle-treated SHR showed increased open-field motor activity (both crossings and rearings) when tested after each week of treatment. The overall hyperactivity of vehicle-treated SHR was significantly reduced to the levels of vehicle-treated WKY rats after 2 and 3 weeks of EGCG treatment. Colonic and duodenal preparations obtained from SHR chronically treated in vivo with EGCG showed reduced responses to carbachol (0.05–5 µM) and increased inhibitory response to electrical field stimulation (EFS, 1–10 Hz, 13 V, 1 msec, 10-sec train duration), respectively. In vitro acute EGCG

  5. Insulin nonattenuation of vasoactive agent-induced responses in mesangial cells from spontaneously hypertensive rats.

    PubMed

    Inishi, Y; Okuda, T; Arakawa, T; Yasuda, C; Ohara, M; Kurokawa, K

    1995-03-01

    We recently found that insulin attenuates intracellular calcium transients and cell contraction caused by vasoactive agents in cultured rat mesangial cells. Because altered glomerular function may be causally related to the evolution of hypertension, we examined in the present study the effects of insulin on the functions of mesangial cells derived from spontaneously hypertensive rats (SHR) of 4- and 8-weeks of age. Age-matched Wistar Kyoto rats (WKY) were used as controls. Intracellular calcium concentration ([Ca2+]i) was measured with Fura-2 method in suspended mesangial cells. Pretreatment of mesangial cells with 5 micrograms/ml insulin for 120 minutes did not affect basal [Ca2+]i in either WKY or SHR mesangial cells. However, insulin pretreatment significantly attenuated [Ca2+]i transients to vasoactive agents in WKY mesangial cells. In contrast, [Ca2+]i transients to these agents were not attenuated by insulin in SHR mesangial cells. Additionally, SHR mesangial cell contraction in response to angiotensin II (Ang II) was not altered by insulin, while WKY mesangial cell contraction to Ang II was, as in normal Wistar rats, significantly reduced by insulin. Since we previously showed the possibility that the attenuation of calcium signal by insulin is via insulin-like growth factor I (IGF-I) receptor, we also examined the effect of IGF-I. In contrast to WKY mesangial cells, IGF-I-induced attenuation of [Ca2+]i responses to platelet activating factor was absent in SHR mesangial cells. [125I]-IGF-I binding in SHR mesangial cells was not significantly different from that in WKY mesangial cells.(ABSTRACT TRUNCATED AT 250 WORDS) PMID:7752589

  6. Captopril improves cerebrovascular structure and function in old hypertensive rats

    PubMed Central

    Dupuis, François; Atkinson, Jeffrey; Limiñana, Patrick; Chillon, Jean-Marc

    2005-01-01

    We examined the effects of an angiotensin-converting enzyme inhibitor (ACEI), captopril, on cerebral arterioles in young and old spontaneously hypertensive rats (SHR). Animals were anesthetized with sodium pentobarbitone (60 mg kg−1 day−1). We measured cerebral blood flow (CBF, arbitrary units) and cerebral arteriolar internal diameter (ID, μm) prior to and during stepwise hypotension (SH) in 6- (WKY-6) and 15-month-old (WKY-15) Wistar Kyoto rats and in age-matched SHR that were untreated (SHR-6 and SHR-15) or treated for 3 months with captopril (SHR-6C, 105±2 mg kg−1 day−1 and SHR-15C, 94±1 mg kg−1 day−1). ID and cross-sectional area of the vessel wall (CSA) were measured in deactivated (EDTA) cerebral arterioles during a second SH. Captopril decreased the lower limit of CBF autoregulation (61±6 in SHR-6C and 51±2 in SHR-15C versus 52±6 in WKY-6 and 62±7 in WKY-15 and 83±14 mmHg in SHR-6 and 120±19 mmHg in SHR-15; P<0.05) and CSA (510±21 in SHR-6C and 585±25 in SHR-15C versus 529±12 in WKY-6 and 549±20 in WKY-15 and 644±38 mmHg in SHR-6 and 704±38 mmHg in SHR-15; P<0.05). Captopril increased cerebral arteriolar external diameter of SHR (105±5 in SHR-6C and 94±4 in SHR-15C vs 125±8 in WKY-6 and 108±3 in WKY-15 and 83±2 mmHg in SHR-6 and 80±2 mmHg in SHR-15 for a pial arteriolar pressure step of 35–39 mmHg; P<0.05). Captopril attenuated increases in cerebral arteriolar distensibility in young SHR. Thus, ACEIs attenuate eutrophic and hypertrophic inward remodeling of cerebral arterioles in young and old SHR, thus decreasing the lower limit of CBF autoregulation. PMID:15655534

  7. Differential changes in atrial natriuretic peptide and vasopressin receptor bindings in kidney of spontaneously hypertensive rat

    SciTech Connect

    Ogura, T.; Mitsui, T.; Yamamoto, I.; Katayama, E.; Ota, Z.; Ogawa, N.

    1987-01-19

    To elucidate the role of atrial natriuretic peptide (ANP) and vasopressin (VP) in a hypertensive state, ANP and VP receptor bindings in spontaneously hypertensive rat (SHR) kidney were analyzed using the radiolabeled receptor assay (RRA) technique. Systolic blood pressure of SHR aged 12 weeks was statistically higher than that of age-matched Wistar Kyoto (WKY) rats. Maximum binding capacity (Bmax) of (/sup 125/I)-ANP binding to the SHR kidney membrane preparations was statistically lower than that of WKY rats, but dissociation constant (Kd) was not significantly different. On the other hand, Bmax of (/sup 3/H)-VP binding to the SHR kidney membrane preparations was statistically higher than that of WKY rats, but Kd were similar. Since the physiological action of ANP is natriuresis and VP is the most important antidiuretic hormone in mammalia, these opposite changes of ANP and VP receptor bindings in SHR kidney suggested that these peptides may play an important role in the pathophysiology of the hypertensive state, although it has not been confirmed as yet.

  8. Effect of nifedipine on coronary capillary geometry in normotensive and hypertensive rats.

    PubMed

    Rakusan, K; Cicutti, N; Kazda, S; Turek, Z

    1994-08-01

    The aim of this study was to describe quantitatively changes in the coronary capillary network resulting from hypertrophy in spontaneously hypertensive rats (SHR) and a potential effect of long-term treatment of these animals with nifedipine. Age-matched male SHR and Wistar-Kyoto (WKY) rats were treated for 27 weeks. Four experimental groups were analyzed: (1) untreated SHR, (2) nifedipine-treated SHR, (3) untreated control WKY rats, and (4) nifedipine-treated WKY rats. Treatment significantly decreased systolic blood pressure in SHR, although normotensive pressures were not reached. SHR had significantly higher cardiac weight, which decreased in nifedipine-treated rats, but values remained above those in control animals. Morphometric evaluation revealed lower capillary density and larger capillary domain area in hearts from SHR, which were partially attenuated by treatment with nifedipine. Capillary domain area was also significantly larger at arteriolar portions compared with domains supplied at venular portions. Capillary segment length was consistently shorter on the venular than arteriolar portion of the capillary, whereas no differences were observed between hearts from WKY rats and SHR. Treatment with nifedipine resulted in a prolongation of segment length. Reconstruction of the three-dimensional capillary supply unit (capillary domain area times capillary segment length) revealed significant differences between the amount of tissue supplied by a capillary at its arteriolar portion than more distally, which was detectable in all experimental groups. In hypertrophic hearts from SHR this tissue volume is increased mainly because of longer intercapillary distances and larger domains, especially on arteriolar portions.(ABSTRACT TRUNCATED AT 250 WORDS) PMID:8039845

  9. α1-Adrenoceptor activation of PKC-ε causes heterologous desensitization of thromboxane receptors in the aorta of spontaneously hypertensive rats

    PubMed Central

    Zhao, Yingzi; Vanhoutte, Paul M; Leung, Susan W S

    2015-01-01

    Background and Purpose In the aorta of adult spontaneously hypertensive (SHR), but not in that of normotensive Wistar-Kyoto (WKY), rats, previous exposure to phenylephrine inhibits subsequent contractions to PGE2. The present experiments were designed to examine the mechanism(s) underlying this inhibition. Experimental Approach Isometric tension was measured in isolated rings of SHR and WKY aortae. Gene expression and protein presence were measured by quantitative real-time PCR and Western blotting respectively. Key Results In aorta of 18 weeks SHR, but not age-matched WKY, pre-exposure to phenylephrine inhibited subsequent contractions to PGE2 that were mediated by thromboxane prostanoid (TP) receptors. This inhibition was not observed in preparations of pre-hypertensive 5-week-old SHR, and was significantly larger in those of 36- than 18-week-old SHR. Pre-exposure to the PKC activator, phorbol 12,13-dibutyrate, also inhibited subsequent contractions to PGE2 in SHR aortae. The selective inhibitor of PKC-ε, ε-V1-2, abolished the desensitization caused by pre-exposure to phenylephrine. Two molecular PKC bands were detected and their relative intensities differed in 36-week-old WKY and SHR vascular smooth muscle. The mRNA expressions of PKC-α, PKC-ε, PK-N2 and PKC-ζ and of G protein-coupled kinase (GRK)-2, GRK4 and β-arrestin2 were higher in SHR than WKY aortae. Conclusions and Implications These experiments suggest that in the SHR but not the WKY aorta, α1-adrenoceptor activation desensitizes TP receptors through activation of PKC-ε. This heterologous desensitization is a consequence of the chronic exposure to high arterial pressure. PMID:25857252

  10. Age-related changes in hypertensive brain damage in the hippocampi of spontaneously hypertensive rats

    PubMed Central

    LI, YALI; LIU, JIAN; GAO, DENGFENG; WEI, JIN; YUAN, HAIFENG; NIU, XIAOLIN; ZHANG, QIAOJUN

    2016-01-01

    The aim of the present study was to investigate the age-related alterations in hypertensive brain damage in the hippocampi of spontaneously hypertensive rats (SHR) and the underlying mechanisms. Aging resulted in a significant increase in the number of activated astrocytes and apoptotic cells in the SHR group, which was accompanied by increased expression of oxidative stress markers (iNOS and gp47phox) and apoptotic regulatory proteins (Bax and caspase-3). In addition, the expression of PPAR-γ and Bcl-2 were progressively reduced with increasing age in the SHR group. The 32 and 64-week-old SHRs exhibited significantly increased numbers of apoptotic cells, oxidative stress markers and pro-apoptotic proteins compared with age-matched WKY rats, which was accompanied by reduced expression of PPAR-γ. Compared with the 16 and 32-week-old WKY group, the 64-week-old WKY rats exhibited increased oxidative stress and pro-apoptotic markers, and increased levels apoptotic cells. In conclusion, the present study indicated that both aging and hypertension enhanced brain damage and oxidative stress injury in the hippocampi of SHRs, indicated by an increased presence of apoptotic cells and astrocytes. In addition, reduced expression of PPAR-γ may contribute to the age-related brain damage in SHRs. PMID:26846626

  11. EXCESSIVE LEUKOTRIENE B4 IN NUCLEUS TRACTUS SOLITARII IS PROHYPERTENSIVE IN SPONTANEOUSLY HYPERTENSIVE RATS

    PubMed Central

    Waki, Hidefumi; Hendy, Emma B.; Hindmarch, Charles C.T.; Gouraud, Sabine; Toward, Marie; Kasparov, Sergey; Murphy, David; Paton, Julian F.R.

    2014-01-01

    Inflammation within the brainstem microvasculature has been associated with chronic cardiovascular diseases. We found that the expression of several enzymes involved in arachidonic acid (AA) - leukotriene B4 (LTB4) production was altered in NTS of SHR. LTB4 produced from AA by 5-lipoxygenase (5LOX) is a potent chemoattractant of leukocytes. Leukotriene B4-12-hydroxydehydrogenase (LTB4-12-HD), which degrades leukotriene B4 (LTB4), was down-regulated compared to Wistar-Kyoto rats (WKY). Quantitative RT-PCR revealed that LTB4-12-HD was reduced by 63 and 58% in the NTS of adult SHR and pre-hypertensive (PH) SHR respectively, compared to age-matched WKY rats (n=6). 5LOX gene expression was up-regulated in the NTS of SHR (~50%; n=6). LTB4 levels were increased in the NTS of the SHR (17%; n=10, p<0.05). LTB4 receptors BLT1 (but not BLT2), were expressed on astroglia in the NTS but not neurons or vessels. Microinjection of LTB4 into the NTS of WKY rats increased both leukocyte adherence and arterial pressure for over 4 days (peak: +15 mmHg; P<0.01). In contrast, blockade of NTS BLT1 receptors lowered blood pressure in the SHR (peak: -13 mmHg; P<0.05) but not WKY rats. Thus, excessive amounts of LTB4 in NTS of SHR possibly as a result of up-regulation of 5LOX and down regulation of LTB412-HD, can induce inflammation. Since blockade of NTS BLT1 receptors lowered arterial pressure in the SHR their endogenous activity may contribute to the hypertensive state of this rodent model. Thus, inflammatory reactions in the brainstem are causally associated with neurogenic hypertension. PMID:23172924

  12. Effect of polyphenol-containing azuki bean (Vigna angularis) extract on blood pressure elevation and macrophage infiltration in the heart and kidney of spontaneously hypertensive rats.

    PubMed

    Sato, Shin; Mukai, Yuuka; Yamate, Jyoji; Kato, Jun; Kurasaki, Masaaki; Hatai, Asako; Sagai, Masaru

    2008-01-01

    1. Hypertension is a major risk factor for myocardial infarction and renal damage, and it has also been shown to have pro-inflammatory actions that increase the formation of reactive oxygen species. Macrophage infiltration has been suggested to play a role in the pathogenesis of hypertension. Azuki beans are known to contain pro-anthocyanidins, a group of polyphenolic bioflavonoids with remarkable radical-scavenging activities in vitro. Therefore, the aim of the present study was to investigate the effect of polyphenol-containing azuki bean extract (ABE) on systolic blood pressure (SBP) and macrophage infiltration in the heart and kidney of spontaneously hypertensive rats (SHR). 2. Spontaneously hypertensive rats and control normotensive Wistar-Kyoto (WKY) rats were divided into two groups fed either 0 or 0.8% ABE in their diets. Tail SBP and macrophage kinetics in the heart and kidney were examined. 3. The SBP of the SHR group was higher than that of age-matched WKY rats throughout the treatment period. After 8 weeks of treatment, the increased SBP in ABE-treated SHR was significantly less than that in untreated SHR. 4. Nicotinamide adenine dinucleotide (NADH) or nicotinamide adenine dinucleotide phosphate (NADPH)-stimulated superoxide (O2-) production was enhanced in the kidney and heart in SHR and WKY rats compared with levels in the absence of NADH or NADPH. The NADPH-stimulated superoxide (O2-) levels in the kidney in untreated SHR was significantly higher than that in untreated WKY rats. The (O2-) levels in ABE-treated SHR were significantly decreased compared with the untreated SHR group. 5. In immunohistochemical analyses, the number of macrophages in the heart and in the glomeruli and tubulointerstitium of the kidney was significantly higher in ABE-untreated SHR than in ABE-untreated WKY rats. Conversely, there was a significant decrease in the number of macrophages in ABE-treated SHR compared with the untreated SHR. There were significant positive

  13. Age and hypertension strongly induce aortic stiffening in rats at basal and matched blood pressure levels.

    PubMed

    Lindesay, George; Ragonnet, Christophe; Chimenti, Stefano; Villeneuve, Nicole; Vayssettes-Courchay, Christine

    2016-05-01

    Age and hypertension are major causes of large artery remodeling and stiffening, a cardiovascular risk factor for heart and kidney damage. The aged spontaneously hypertensive rat (SHR) model is recognized for human cardiovascular pathology, but discrepancies appeared in studies of arterial stiffness. We performed experiments using a robust analysis via echo tracking in 20-week adult (n = 8) and 80-week-old SHR (n = 7), with age-matched normotensive Wistar Kyoto rats (WKY, n = 6;6) at basal and matched levels of blood pressure (BP). After anesthesia with pentobarbital, abdominal aortic diameter and pressure were recorded and BP was decreased by clonidine i.v. At basal BP, aortic pulse distension, compliance, and distensibility (AD) were reduced and stiffness index increased with age and hypertension and further altered with age + hypertension. When BP was adjusted in SHR to that of normotensive rats (130 mmHg), there was no difference between 20-week-old SHR and WKY Importantly, the age effect was maintained in both WKY and SHR and accentuated by hypertension in old rats. At 130 mmHg, with similar pulse pressure in the four groups, AD (kPa(-3)) = 24.2 ± 1 in 20 weeks WKY, 19.7 ± 1.4 in 20 weeks SHR, 12.4 ± 1.3 in 80 weeks WKY and 6.6 ± 0.6 in 80 weeks SHR; distension = 7.6 ± 0.4%, 6.7 ± 0.6%, 3.7 ± 0.3%, and 1.8 ± 0.2% in the same groups. In conclusion, reduced distensibility, that is, stiffening due to age is clearly shown here in both WKY and SHR as well as a synergistic effect of age and hypertension. This technique will allow new studies on the mechanisms responsible and drug intervention. PMID:27233301

  14. Early Training-Induced Reduction of Angiotensinogen in Autonomic Areas—The Main Effect of Exercise on Brain Renin-Angiotensin System in Hypertensive Rats

    PubMed Central

    Chaar, Laiali Jurdi; Alves, Tatiana Pereira; Batista Junior, Alvaro Martins; Michelini, Lisete Compagno

    2015-01-01

    Background Exercise training (T) blunts functional deficits and renin-angiotensin system (RAS) hyperactivity in hypertensive individuals. There is no information on T-induced temporal changes of brain RAS. We evaluate now the simultaneous effects of T on functional responses and time course changes in the expression/activity of brain RAS components in autonomic cardiovascular-controlling areas. Methods and Results Spontaneously hypertensive rats (SHR) and age-matched normotensive controls (WKY) were trained for 0, 1, 2, 4, 8 and 12 weeks. Sedentary (S) groups served as time-controls. After arterial pressure (AP) and heart rate (HR) recordings at rest, fresh and fixed brains were harvested for qPCR and immunofluorescence assays. SHR-S vs. WKY-S exhibited higher mean AP (MAP) and HR, increased pressure variability and sympathetic activity, elevated AT1 receptor (AT1) expression in nucleus tractus solitarii (NTS) and higher Mas receptor expression in the rostroventrolateral medulla (RVLM). In SHR, T promptly (T2 on) reduced sympathetic variability to heart/vessels and largely decreased angiotensinogen expression in the paraventricular hypothalamic nucleus (PVN) and NTS, with a late RVLM reduction (T4). AT1 expression was only reduced at T12 (PVN and NTS) with transient, not maintained Mas receptor changes in PVN and RVLM. These responses were accompanied by baseline MAP and HR reduction in the SHR-T (from T4 on). In the SHR group, PVN angiotensinogen expression correlated positively with sympathetic activity, resting MAP and HR. In WKY-T, a precocious (T2-T12) RVLM AT1 decrease preceded the appearance of resting bradycardia (from T8 on). Conclusions Early and maintained reduction of angiotensinogen content in autonomic areas of the SHR is the most prominent effect of training on brain RAS. Down-regulation of PVN RAS expression is an essential factor to drive cardiovascular benefits in SHR-T, while resting bradycardia in WKY-T is correlated to RVLM AT1 reduction. PMID

  15. Gene Expression Suggests Spontaneously Hypertensive Rats May Have Altered Metabolism and Reduced Hypoxic Tolerance

    PubMed Central

    Ritz, Marie-Françoise; Grond-Ginsbach, Caspar; Engelter, Stefan; Lyrer, Philippe

    2012-01-01

    Cerebral small vessel disease (SVD) is an important cause of stroke, cognitive decline and vascular dementia (VaD). It is associated with diffuse white matter abnormalities and small deep cerebral ischemic infarcts. The molecular mechanisms involved in the development and progression of SVD are unclear. As hypertension is a major risk factor for developing SVD, Spontaneously Hypertensive Rats (SHR) are considered an appropriate experimental model for SVD. Prior work suggested an imbalance between the number of blood microvessels and astrocytes at the level of the neurovascular unit in 2-month-old SHR, leading to neuronal hypoxia in the brain of 9-month-old animals. To identify genes and pathways involved in the development of SVD, we compared the gene expression profile in the cortex of 2 and 9-month-old of SHR with age-matched normotensive Wistar Kyoto (WKY) rats using microarray-based technology. The results revealed significant differences in expression of genes involved in energy and lipid metabolisms, mitochondrial functions, oxidative stress and ischemic responses between both groups. These results strongly suggest that SHR suffer from chronic hypoxia, and therefore are unable to tolerate ischemia-like conditions, and are more vulnerable to high-energy needs than WKY. This molecular analysis gives new insights about pathways accounting for the development of SVD. PMID:22272763

  16. Expression of proteins associated with adipocyte lipolysis was significantly changed in the adipose tissues of the obese spontaneously hypertensive/NDmcr-cp rat

    PubMed Central

    2014-01-01

    Background The etiology of the metabolic syndrome is complex, and is determined by the interplay of both genetic and environmental factors. The present study was designed to identify genes and proteins in the adipose tissues with altered expression in the spontaneously hypertensive/NIH –corpulent rat, SHR/NDmcr-cp (CP) and to find possible molecular targets associated with the pathogenesis or progression of obesity related to the metabolic syndrome. Methods We extracted RNAs and proteins from the epididymal adipose tissues in CP, SHR/Lean (Lean), and Wistar Kyoto (WKY) rats and performed microarray analysis and two-dimensional difference in gel electrophoresis (2D-DIGE) linked to a matrix-assisted laser desorption ionization time-of-flight tandem mass spectrometry (MALDI-TOF/TOF MS). Results The results showed different mRNA and protein expression levels in the adipose tissue: oligo DNA microarray identified 33 genes that were significantly (P < 0.01) up-regulated and 17 genes significantly down-regulated in CP compared with WKY and Lean rats at both 6 and 25 weeks of age. The affected genes-proteins were associated with lipolytic enzymes stimulated by peroxisome proliferator-activated receptor (PPAR) signaling. Further analysis using the 2D-DIGE connected with MALDI-TOF/TOF analysis, the expression of monoglyceride lipase (MGLL) was significantly up-regulated and that of carboxylesterase 3 (CES3) was significantly down-regulated in 6- and 25-week-old CP compared with age-matched control (WKY and Lean rats). Conclusions Our results suggest the possible involvement of proteins associated with adipocyte lipolysis in obesity related to the metabolic syndrome. PMID:24468282

  17. Antidepressant-like Effects of Buprenorphine in Rats Are Strain Dependent

    PubMed Central

    Browne, Caroline A.; van Nest, Duncan; Lucki, Irwin

    2014-01-01

    The prevalence of major depressive disorder and the limited efficacy of conventional drug treatments provide significant impetus to develop novel and more rapidly acting antidepressants for individuals with treatment resistant forms of depression. The primary goal of these studies was to ascertain whether buprenorphine (BPN), a medically available drug with mixed effects at opioid receptors, was effective in behavioral tests using the Wistar Kyoto (WKY) rat strain, a rodent model of exaggerated depressive and anxiety behaviors that demonstrates resistance to certain antidepressants. As WKY rats are maintained by different sources, we assessed the behavioral effects of BPN using the modified rat forced swim test (FST) and the emergence test in WKY rat colonies obtained from different vendors. BPN dose-dependently reduced immobility and increased swimming behavior in the FST and reduced emergence latencies in two WKY lines (Charles River (WKY/NCrl) and Harlan laboratories (WKY/NHsd)) that also showed high baseline immobility in the FST. WKY rats from Taconic (WKY/NTac) did not show high baseline immobility in the FST or anxiety as had been previously reported, suggesting drift in the phenotype of rats from this supplier. Furthermore, BPN did not reduce immobility in the FST or reduce latencies in the emergence test in WKY rats from Taconic. BPN also failed to produce antidepressant-like effects in Wistar and Sprague-Dawley rats. These results indicate a striking strain-selectivity for the effects of BPN, producing antidepressant and anxiolytic-like responses in WKY/NCrl and WKY/NHsd lines but not in the normosensitive control Wistar and Sprague-Dawley strains. PMID:25453747

  18. Electrophysiological Neuroimaging using sLORETA Comparing 22 Age Matched Male and Female Schizophrenia Patients

    PubMed Central

    Eugene, Andy R.; Masiak, Jolanta; Kapica, Jacek; Masiak, Marek

    2015-01-01

    Introduction The purpose of this electrophysiological neuroimaging study was to provide a deeper mechanistic understanding of both olanzapine and risperidone pharmacodynamics relative to gender. In doing so, we age-matched 22 men and women and evaluated their resting-state EEG recordings and later used standard low resolution brain Electrotomography to visualize the differences in brain activity amongst the two patient groups. Methods In this investigation, electroencephalogram (EEG) data were analyzed from male and female schizophrenia patients treated with either olanzapine or risperidone, both atypical antipsychotics, during their in-patient stay at the Department of Psychiatry. Twenty-two males and females were age-matched and EEG recordings were analyzed from 19 Ag/AgCl electrodes. Thirty-seconds of resting EEG were spectrally transformed in standardized low resolution electromagnetic tomography (sLORETA). 3D statistical non-paramentric maps for the sLORETA Global Field Power within each band were finally computed. Results The results indicated that, relative to males patients, females schizophrenia patients had increased neuronal synchronization in delta frequency, slow-wave, EEG band located in the dorsolateral prefrontal cortex, within the middle frontal gyrus (t= -2.881, p < 0.03580). These findings suggest that females experience greater dopamine (D2) receptor and serotonin (5-HT2) receptor neuronal blockade relative to age-matched males. Further, our finding provided insight to the pharmacodynamics of second-generation antipsychotics olanzapine and risperidone. Conclusion When compared to male patients, female patients, suffering from schizophrenia, have D2 and 5-HT2 receptors that are blocked more readily than age-matched male schizophrenia patients. Clinically, this may translate into a quicker time to treatment-response in females as compared to male patients. PMID:26617679

  19. Cocaine self-administration in Wistar-Kyoto rats: a behavioral and biochemical analysis.

    PubMed

    Jastrzębska, Joanna; Frankowska, Małgorzata; Szumiec, Łukasz; Sadakierska-Chudy, Anna; Haduch, Anna; Smaga, Irena; Bystrowska, Beata; Daniel, Wladyslawa A; Filip, Małgorzata

    2015-10-15

    Depression and cocaine abuse disorders are common concurrent diagnoses. In the present study, we employed Wistar-Kyoto (WKY) rats that showed a depressive-like phenotype to study intravenous cocaine self-administration and extinction/reinstatement procedures. We also investigated the basal tissue level of neurotransmitters, their metabolites and plasma corticosterone (CORT) concentrations in WKY rats, bulbectomized (OBX) rats, and control rats. The WKY rats exhibited an attenuation of the cocaine-associated lever presses and cocaine intake during the acquisition/maintenance of cocaine self-administration only under specific conditions. Active lever presses exhibited by the WKY rats and control animals did not differ during the extinction training and cocaine-seeking behaviors. The WKY rats demonstrated alterations in the basal levels of dopamine, norepinephrine, and serotonin in selected brain structures involved in depression and drug addiction. The changes in the level of neurotransmitters in these animals refer not only to the control (Wistar) rats but also to bulbectomized animals, which represent another depression model. Furthermore, we identified unchanged levels of CORT in the WKY and OBX rats during the light phase and free-stress conditions. This finding suggests that WKY rats should not be used to investigate the co-occurrence of depression and cocaine addiction, as this rat strain does not show an enhanced risk of relapse. PMID:26192911

  20. Electrical stimulation directs engineered cardiac tissue to an age-matched native phenotype

    PubMed Central

    Lasher, Richard A; Pahnke, Aric Q; Johnson, Jeffrey M; Sachse, Frank B

    2012-01-01

    Quantifying structural features of native myocardium in engineered tissue is essential for creating functional tissue that can serve as a surrogate for in vitro testing or the eventual replacement of diseased or injured myocardium. We applied three-dimensional confocal imaging and image analysis to quantitatively describe the features of native and engineered cardiac tissue. Quantitative analysis methods were developed and applied to test the hypothesis that environmental cues direct engineered tissue toward a phenotype resembling that of age-matched native myocardium. The analytical approach was applied to engineered cardiac tissue with and without the application of electrical stimulation as well as to age-matched and adult native tissue. Individual myocytes were segmented from confocal image stacks and assigned a coordinate system from which measures of cell geometry and connexin-43 spatial distribution were calculated. The data were collected from 9 nonstimulated and 12 electrically stimulated engineered tissue constructs and 5 postnatal day 12 and 7 adult hearts. The myocyte volume fraction was nearly double in stimulated engineered tissue compared to nonstimulated engineered tissue (0.34 ± 0.14 vs 0.18 ± 0.06) but less than half of the native postnatal day 12 (0.90 ± 0.06) and adult (0.91 ± 0.04) myocardium. The myocytes under electrical stimulation were more elongated compared to nonstimulated myocytes and exhibited similar lengths, widths, and heights as in age-matched myocardium. Furthermore, the percentage of connexin-43-positive membrane staining was similar in the electrically stimulated, postnatal day 12, and adult myocytes, whereas it was significantly lower in the nonstimulated myocytes. Connexin-43 was found to be primarily located at cell ends for adult myocytes and irregularly but densely clustered over the membranes of nonstimulated, stimulated, and postnatal day 12 myocytes. These findings support our hypothesis and reveal that the

  1. *GAS-PHASE AND PARTICULATE COMPONENTS OF DIESEL EXHAUST PRODUCE DIFFERENTIAL CARDIOPHYSIOLOGICAL IMPAIRMENTS IN HEALTHY RATS

    EPA Science Inventory

    We recently showed that inhalation exposure of normotensive Wistar Kyoto (WKY) rats to whole diesel exhaust (DE) elicited changes in cardiac gene expression pattern that broadly mimicked gene expression in non-exposed spontaneously hypertensive rats. We hypothesized that healthy ...

  2. Prevalence of temporomandibular disorder pain in Chinese adolescents compared to an age-matched Swedish population.

    PubMed

    Hongxing, L; Astrøm, A N; List, T; Nilsson, I-M; Johansson, A

    2016-04-01

    This study aimed to (i) assess the prevalence and perceived need for treatment of TMD pain, and its association with socio-economic factors and gender, in adolescents in Xi᾽an, Shaanxi Province, China, and (ii) compare the prevalence and association with gender of TMD pain in Xi᾽an to an age-matched Swedish population. We surveyed Chinese adolescents aged 15 to 19 years in Xi'an, China (n = 5524), using a questionnaire with two-stage stratified sampling and the school as the sampling unit. The study included second-year students at selected high schools. It also included an age-matched Swedish population (n = 17 015) surveyed using the same diagnostic criteria for TMD pain as that used in the Chinese sample. The survey found TMD pain in 14·8% (n = 817) of the Chinese sample and 5·1% (n = 871) of the Swedish sample (P < 0·0001). Girls had significantly more TMD pain than boys in both the Chinese (P < 0·05) and Swedish (P < 0·001) samples. TMD pain increased with age in the Chinese population. Of the Chinese adolescents with TMD pain, 47% reported that they felt a need for treatment. Rural schools, low paternal education levels, poverty, living outside the home, poor general and oral health, and dissatisfaction with teeth all showed significant positive correlations with TMD pain. Prevalence of TMD pain in Chinese adolescents was significantly higher than in the Swedish sample. PMID:26538188

  3. Increasing oxidative stress with molsidomine increases blood pressure in genetically hypertensive rats but not normotensive controls.

    PubMed

    Fortepiani, Lourdes A; Reckelhoff, Jane F

    2005-09-01

    Spontaneously hypertensive rats (SHR) have a higher level of oxidative stress and exhibit a greater depressor response to a superoxide scavenger, tempol, than normotensive Wistar-Kyoto rats (WKY). This study determined whether an increase in oxidative stress with a superoxide/NO donor, molsidomine, would amplify the blood pressure in SHR. Male SHR and WKY were given molsidomine (30 mg.kg(-1).day(-1)) or vehicle (0.01% ethanol) for 1 wk, and blood pressure, renal hemodynamics, nitrate and nitrite excretion (NOx), renal superoxide production, and expression of renal antioxidant enzymes, Mn- and Cu,Zn-SOD, catalase, and glutathione peroxidase (GPx), were measured. Renal superoxide and NOx were higher in control SHR than in WKY. Molsidomine increased superoxide by approximately 35% and NOx by 250% in both SHR and WKY. Mean arterial blood pressure (MAP) was also higher in control SHR than WKY. Molsidomine increased MAP by 14% and caused renal vasoconstriction in SHR but reduced MAP by 16%, with no effect on renal hemodynamics, in WKY. Renal expression of Mn- and Cu,Zn-SOD was not different between SHR and WKY, but expression of catalase and GPx were approximately 30% lower in kidney of SHR than WKY. The levels of Mn- and Cu,Zn-SOD were not increased with molsidomine in either WKY or SHR. Renal catalase and GPx expression was increased by 300-400% with molsidomine in WKY, but there was no effect in SHR. Increasing oxidative stress elevated blood pressure further in SHR but not WKY. WKY are likely protected because of higher bioavailable levels of NO and the ability to upregulate catalase and GPx. PMID:15905221

  4. Blood Pressure Interventions Affect Acute and Four-Week Diesel Exhaust Induced Pulmonary Injury in Healthy and Hypertensive Rats

    EPA Science Inventory

    Rationale: We recently showed that inhalation exposure of normotensive Wistar Kyoto (WKY) rats to whole diesel exhaust (DE) elicits changes in cardiac gene expression that broadly mimics expression in spontaneously hypertensive (SH) rats without DE. We hypothesized that pharmacol...

  5. Heroin snorters versus injectors: comparison on drug use and treatment outcome in age-matched samples.

    PubMed

    Carpenter, M J; Chutuape, M A; Stitzer, M L

    1998-12-01

    Drug use histories and treatment outcomes were compared for age, race and gender-matched samples of intravenous (IV; n = 28) versus intranasal (IN; n = 28) opiate abusers entering a 3-day inpatient detoxification unit. Data were derived from the Addiction Severity Index (ASI) interview. Both groups reported daily heroin use prior to detoxification, but IV users reported more days of alcohol and multiple drug use during the past 30 days. Despite age matching, IV users also started using alcohol at an earlier age and accumulated more lifetime months of regular alcohol, cocaine and multidrug use. IV users were more likely to enter treatment following the detox, but no significant outcome differences were noted at 1 and 3 months post-detoxification. The results show that intravenous, as compared to intranasal, opiate users have both a more severe pattern and a more extensive history of the use of non-opiate drugs. PMID:10933336

  6. Neural mechanisms of verb argument structure processing in agrammatic aphasic and healthy age-matched listeners

    PubMed Central

    Thompson, C.K.; Bonakdarpour, B.; Fix, S.F.

    2010-01-01

    Processing of lexical verbs involves automatic access to argument structure entries entailed within the verb's representation. Recent neuroimaging studies with young normal listeners suggest that this involves bilateral posterior perisylvian tissue, with graded activation in these regions based on argument structure complexity. The aim of the present study was to examine the neural mechanisms of verb processing using functional magnetic resonance imaging (fMRI) in older normal volunteers and patients with stroke-induced agrammatic aphasia, a syndrome in which verb, as compared to noun, production often is selectively impaired, but verb comprehension in both on-line and off-line tasks is spared. Fourteen healthy listeners and five age-matched aphasic patients performed a lexical decision task, which examined verb processing by argument structure complexity, i.e., one-argument (i.e., intransitive (v1)); two-argument (i.e., transitive (v2)), and three-argument (v3) verbs. Results for the age-matched listeners largely replicated those for younger participants studied by Thompson et al. (2007): v3-v1 comparisons showed activation of the angular gyrus in both hemispheres and this same heteromodal region was activated in the left hemisphere in the (v2+v3)-v1 contrast. Similar results were derived for the agrammatic aphasic patients, however, activation was unilateral (in the right hemisphere for 3 participants) rather than bilateral likely because these patients' lesions extended to the left temporoparietal region. All performed the task with high accuracy and, despite differences in lesion site and extent, they recruited spared tissue in the same regions as healthy normals. Consistent with psycholinguistic models of sentence processing, these findings indicate that the posterior language network is engaged for processing verb argument structure and is crucial for semantic integration of argument structure information. PMID:19702460

  7. Comparative Analysis of Mechanical Properties of PWV, NO and Ascending Aorta between WHY Rats and SHR Rats

    PubMed Central

    Yu, Bo; Xu, De-Jun; Sun, Huan; Yang, Kun; Luo, Min

    2015-01-01

    Background The aim of this study was to compare and analyze the tensile mechanical properties of the ascending aorta (AA) in Wistar Kyoto (WKY) rats and spontaneously hypertensive rats (SHRs), for the purpose of providing a biomechanical basis for hypertension prevention. Methods Pulse wave velocities (PWV) and serum nitric oxide (NO) concentrations were determined in 6-month-old WKY rats and SHRs (n = 21, n = 21, respectively). Then, 20 AAs from each group were obtained for longitudinal tensile testing. Results The maximum stress, maximum strain, and strain at a tensile stress of 16 Kpa were greater in WKY rats than in SHRs (p < 0.05). The aortic elastic modulus and PWV value were greater in SHRs than in WKY rats (p < 0.05 for both), while NO concentrations were lower in the SHR group than in the WKY group (p < 0.05). Conclusions The AA tensile mechanical properties differed between the WKY rats and SHRs, and the tensile mechanical properties of the SHR model had changed. PMID:27122902

  8. Year-long antihypertensive therapy with candesartan completely prevents development of cardiovascular organ injuries in spontaneously hypertensive rats.

    PubMed

    Ishimitsu, Toshihiko; Honda, Takeaki; Ohno, Eri; Furukata, Satoshi; Sudo, Yasuyo; Nakano, Nobuyuki; Takahashi, Toshiaki; Ono, Hidehiko; Matsuoka, Hiroaki

    2010-01-01

    Most previous studies have examined the effects of antihypertensive drugs in hypertensive animals for only a few months, and little information has been provided as to the protective effects of lifetime antihypertensive medication against cardiovascular organ injury. In this study, spontaneously hypertensive rats (SHR) were treated for 1 year with an angiotensin-II receptor antagonist (ARB) and the development of hypertensive organ injury was evaluated. Male 15-week-old SHR (n = 9) were given 25 mg/L candesartan (CS) in their drinking water for 1 year. Twelve SHR and 9 normotensive Wistar-Kyoto rats (WKY) were given normal tap water. Tail-cuff blood pressure was almost normalized by CS throughout 1 year (at 12-months: WKY 132 ± 3, SHR 229 ± 3, CS 137 ± 4 mmHg). After 1 year, cardiac ventricular weight (SHR +33%, CS -2% versus WKY) and aortic thickness (SHR +34%, CS +4% versus WKY) in the CS-treated SHR rats were not different than those of WKY. Echocardiographic midwall fractional shortening (SHR -18%, CS -1% versus WKY) and left ventricular hydroxyproline content (SHR +47%, CS +11% versus WKY) were also improved by CS to the WKY level. With respect to kidney function, GFR (SHR -24%, CS +9% versus WKY) was preserved, proteinuria (SHR +312%, CS +12% versus WKY) was reduced, and the histological glomerular injury rate (SHR +186%, CS +6% versus WKY) was reduced by CS. These results suggest that long-term antihypertensive therapy with CS can completely prevent hypertensive cardiovascular and renal injuries in SHR. PMID:20966610

  9. Cold-restraint induced gastric lesions in normotensive and spontaneously hypertensive rats

    SciTech Connect

    Athey, G.R.; Iams, S.G.

    1981-02-23

    Spontaneously hypertensive (SHR) rats and normotensive Wistar-Kyoto (WKY) rats were subjected to 2 hr of cold-restraint stress at 4-6/sup o/C following a 24 hr fast. WKY rats had a significantly greater incidence and degree of ulceration of the gastric glandular mucosa than did SHR rats. Mean arterial pressure, obtained from a chronic arterial cannula, fell during 2 hr of cold-restraint stress in both SHR and WKY rats. Heart rate was unchanged in WKY but fell significantly in SHR. Plasma norepinephrine (NE) and epinephrine (E), determined by radioenzymatic assay, increased significantly following stress. Increased levels of NE remained similar for both SHR and WKY rats, while post-stress levels of E for the SHR rats greatly exceeded E levels for WKY rats. A greater degree of hypothermia was also noted in SHR rats. Decreased stress induced ulcerogenesis in the SHR may be due to the well-known altered hemodynamic and autonomic nervous system reactivity in this strain or other factors not yet discovered.

  10. Down-regulation of. alpha. sub 2 adrenoceptors in ventrolateral medulla of spontaneously hypertensive rats

    SciTech Connect

    Gulati, A. )

    1991-01-01

    The binding of ({sup 3}H)idaxazon to imidazole sites and ({sup 3}H)rauwolscine to {alpha}{sub 2} adrenoceptors of neuronal membranes prepared from cerebral cortex and ventrolateral medulla of 10 week old spontaneously hypertensive (SHR) and normotensive Wistar-Kyoto (WKY) rats was determined. ({sup 3}H)idaxazon bound to the membranes of cerebral cortex and ventrolateral medulla at a single high affinity site. The binding of ({sup 3}H)idaxazon in ventrolateral medulla and cerebral cortex was found to be similar in SHR and WKY rats. ({sup 3}H)Rauwolscine bound to the membranes of cerebral cortex and ventrolateral medulla at a single high affinity site. The binding of ({sup 3}H)rauwolscine in the cerebral cortex was found to be similar in SHR and WKY rats. However, in the ventrolateral medulla ({sup 3}H)rauwolscine binding was found to be significantly lower in SHR as compared to WKY rats. The decreased binding was due a decrease (32%) in the B{sub max} value in SHR rats as compared to WKY rats. The K{sub d} values were similar in SHR and WKY rats. It is concluded that imidazole binding sites are not affected while, {alpha}{sub 2} adrenergic binding sites are decreased in the ventrolateral medulla of SHR rats and may be contributing to the regulation of blood pressure.

  11. Comparison of Conditioning Impairments in Children with Down Syndrome, Autistic Spectrum Disorders and Mental Age-Matched Controls

    ERIC Educational Resources Information Center

    Reed, P.; Staytom, L.; Stott, S.; Truzoli, R.

    2011-01-01

    Background: This study investigated the relative ease of learning across four tasks suggested by an adaptation of Thomas's hierarchy of learning in children with Down syndrome, autism spectrum disorders and mental age-matched controls. Methods: Learning trials were carried out to investigate observational learning, instrumental learning, reversal…

  12. Tuberoinfundibular transport of intrahypothalamic-administered dopamine in normo- and hypertensive rats

    SciTech Connect

    Sim, M.K.

    1988-01-01

    The dopamine transport system in the tuberoinfundibular tract of the spontaneously hypertensive (SHR), Wistar Kyoto (WKY) and Sprague-Dawley (SD) rats was investigated. The results show that the rate of dopamine transport in this tract is strain-specific. SD rats transported twice as much dopamine (in 30 minutes) as WKY and SHR. The dopamine transport system in the SHR, being at par with that of the WKY, remained intact. These findings suggest that hypertension and the alleged reduced central dopaminergic activity in the SHR is not related to the transport of dopamine in the tuberoinfundibular tract.

  13. THE MECHANISM OF PARTICULATE MATTER (PM)-ASSOCIATED ZINC IN CARDIAC INJURY IN WISTAR KYOTO RATS.

    EPA Science Inventory

    We have recently found that inhaled combustion particulate matter (PM) with leachable zinc causes myocardial damage without significant pulmonary inflammation or remodeling; this damage is histologically demonstrable in Wistar Kyoto (WKY) rats. Cardiac injury from PM exposure can...

  14. Exposure for ultrafine carbon particles at levels below detectable pulmonary inflammation affects cardiovascular performance in spontaneously hypertensive rats*

    EPA Science Inventory

    Rationale: Exposure to particulate matter is a risk factor for cardiopulmonary disease but the related molecular mechanisms are poorly understood. Previously we studied cardiovascular responses in healthy WKY rats following inhalation exposure to ultrafine carbon particles (UfCPs...

  15. The antihypertensive effect of ethyl acetate extract from red raspberry fruit in hypertensive rats

    PubMed Central

    Jia, Han; Liu, Ji Wen; Ufur, Halmurat; He, Geng Sheng; Liqian, Hai; Chen, Peipei

    2011-01-01

    Objectives: To evaluate the antihypertensive effect of Xinjiang red raspberry fruit ethyl acetate extract (EER) on spontaneously hypertensive rats (SHR) and its possible mechanism from antioxidant perspective. Materials and Methods: The SHR rats were randomly divided into 3 groups, and treated with EER low dose (EERL, 100 mg/kg/d), high dose (EERH, 200 mg/kg/d), and water (SHR) through gastric gavage daily for 5 weeks. Another 8 age-matched male Wistar–Kyoto rats were used as normotensive group (WKY). The systolic blood pressure (SBP) was measured by noninvasive tail-cuff method once a week. At the end of the treatment, blood samples were collected and serum concentrations of nitric oxide (NO), superoxide dismutase (SOD), malondialchehyche (MDA), and plasma endothelin (ET) were determined. Results: Treatment of SHR rats with EER lowered the blood pressure compared with that treated with water (SHR), and the high dose showed more significant reduction in blood pressure. Treatment of SHR rats with EER increased serum NO and SOD levels and lowered ET and MDA levels. As compared with control group, NO levels were increased significantly in EERL (P < 0.01), SOD was elevated more significantly in both EERL and EERH (P < 0.01); MDA was decreased significantly in EERH group (P < 0.05), whereas plasma ET decreased more significantly in the EERH group (P < 0.05). Conclusions: The red raspberry extracts demonstrated a dose-dependent antihypertensive effects in SHR and this may be related to increased NO activation and improved vascular endothelial dysfunction via antioxidation. These results confirmed that raspberries rich in polyphenols have potential cardiovascular protective effects. PMID:21472074

  16. Comparative Toxicity of Biodiesel Exhaust and Petroleum Diesel Exhaust Particulate Matter Using WKY Rat Alveolar Machrophages

    EPA Science Inventory

    Exposure to fine ambient particulate matter <2.5um (PM2.5) can induce airway inflammation, cardiopulmonary morbidity and mortality. Combustion of petroleum diesel and biodiesel contributes to PM2.5. Possible toxicity caused by inhalation of biodiesel emission particles (BioDEP) h...

  17. DIFFERENTIAL CARDIAC SUSCEPTIBILITY OF WISTAR KYOTO (WKY) AND SPONTANEOUSLY HYPERTENSIVE RATS (SHR) TO DIESEL EXHAUST EXPOSURE

    EPA Science Inventory

    Exposure to diesel exhaust particles (DEP) is linked to increases in cardiovascular effects. This is enhanced in individuals with pre-existing disease. Animal models of cardiovascular disease are used to study this susceptibility. The heart is rich in mitochondria, which produce ...

  18. Functional evidence of inhibitory reno-renal reflexes in spontaneously hypertensive rats.

    PubMed

    Protasoni, G; Golin, R; Genovesi, S; Zanchetti, A; Stella, A

    1996-09-01

    The experiments were performed to study the role of the renal nerves and the reno-renal reflexes in the control of water and sodium excretion in spontaneously hypertensive rats (SHR) compared to their normotensive controls, Wistar Kyoto (WKY) rats. Unilateral renal denervation in anaesthetized animals produced a slight, progressive decrease in arterial pressure in both WKY and SHR rats. The glomerular filtration rate temporarily increased in the kidney that underwent the denervation in the SHR group only. After unilateral renal denervation a sharp increase in water and sodium excretion from the ipsilateral kidney was observed in both WKY and SHR. One hour after the denervation, the percent changes in water and sodium excretion were smaller in WKY (+32 +/- 19% and +24 +/- 17%) than in SHR rats (+84 +/- 15% and +93 +/- 20%). In the kidney contralateral to the denervation a reduction in water and sodium excretion was observed and this reduction was prompter in SHR than in WKY rats. One hour after the denervation, the percent changes in water and sodium excretion were similar in WKY (-21 +/- 8% and -18 +/- 7%) and SHR (-19 +/- 6% and -19 +/- 7%). In control groups, sham denervation did not cause significant changes in glomerular filtration rate, and urinary water and sodium excretion. Arterial pressure slightly and progressively decreased in both control groups. Electrical stimulation of the efferent renal nerves performed in WKY and SHR produced similar decreases in renal blood flow, glomerular filtration rate, and water and sodium excretion in the two groups for the same frequencies of stimulation. As this finding indicates that renal targets in hypertensive rats are normally responsive to the neural drive, our data demonstrate that renal responses to unilateral renal denervation in hypertensive rats are equal to the responses observed in normotensive rats. Our results indicate that tonically active inhibitory renorenal reflexes normally operate in spontaneously

  19. UPREGULATION OF BRAIN-DERIVED NEUROTROPHIC FACTOR EXPRESSION IN NODOSE GANGLIA AND THE LOWER BRAINSTEM OF HYPERTENSIVE RATS

    PubMed Central

    Vermehren-Schmaedick, Anke; Jenkins, Victoria K.; Hsieh, Hui-ya; Brown, Alexandra L.; Page, Mollie P.; Brooks, Virginia L.; Balkowiec, Agnieszka

    2014-01-01

    Hypertension leads to structural and functional changes at baroreceptor synapses in the medial nucleus tractus solitarius (NTS), but the underlying molecular mechanisms remain unknown. Our previous studies show that brain-derived neurotrophic factor (BDNF) is abundantly expressed by rat nodose ganglion (NG) neurons, including baroreceptor afferents and their central terminals in the medial NTS. We hypothesized that hypertension leads to upregulation of BDNF expression in NG neurons. To test this hypothesis, we used two mechanistically distinct models of hypertension: the spontaneously hypertensive rat (SHR) and the deoxycorticosterone acetate (DOCA)-salt rat. Young adult SHRs, whose blood pressure was significantly elevated compared to age-matched Wistar-Kyoto (WKY) control rats, exhibited dramatic upregulation of BDNF mRNA and protein in the NG. BDNF transcripts from exon 4, known to be regulated by activity, and exon 9 (protein-coding region) showed the largest increases. Electrical stimulation of dispersed NG neurons with patterns that mimic baroreceptor activity during blood pressure elevations led to increases in BDNF mRNA that were also mediated through promoter 4. The increase in BDNF content of the NG in vivo was associated with a significant increase in the percentage of BDNF-immunoreactive NG neurons. Moreover, upregulation of BDNF in cell bodies of NG neurons was accompanied by a significant increase in BDNF in the NTS region, the primary central target of NG afferents. A dramatic increase in BDNF in the NG was also detected in DOCA-salt hypertensive rats. Together, our study identifies BDNF as a candidate molecular mediator of activity-dependent changes at baroafferent synapses during hypertension. PMID:23172808

  20. Upregulation of brain-derived neurotrophic factor expression in nodose ganglia and the lower brainstem of hypertensive rats.

    PubMed

    Vermehren-Schmaedick, Anke; Jenkins, Victoria K; Hsieh, Hui-ya; Brown, Alexandra L; Page, Mollie P; Brooks, Virginia L; Balkowiec, Agnieszka

    2013-02-01

    Hypertension leads to structural and functional changes at baroreceptor synapses in the medial nucleus tractus solitarius (NTS), but the underlying molecular mechanisms remain unknown. Our previous studies show that brain-derived neurotrophic factor (BDNF) is abundantly expressed by rat nodose ganglion (NG) neurons, including baroreceptor afferents and their central terminals in the medial NTS. We hypothesized that hypertension leads to upregulation of BDNF expression in NG neurons. To test this hypothesis, we used two mechanistically distinct models of hypertension, the spontaneously hypertensive rat (SHR) and the deoxycorticosterone acetate (DOCA)-salt rat. Young adult SHRs, whose blood pressure was significantly elevated compared with age-matched Wistar-Kyoto (WKY) control rats, exhibited dramatic upregulation of BDNF mRNA and protein in the NG. BDNF transcripts from exon 4, known to be regulated by activity, and exon 9 (protein-coding region) showed the largest increases. Electrical stimulation of dispersed NG neurons with patterns that mimic baroreceptor activity during blood pressure elevations led to increases in BDNF mRNA that were also mediated through promoter 4. The increase in BDNF content of the NG in vivo was associated with a significant increase in the percentage of BDNF-immunoreactive NG neurons. Moreover, upregulation of BDNF in cell bodies of NG neurons was accompanied by a significant increase in BDNF in the NTS region, the primary central target of NG afferents. A dramatic increase in BDNF in the NG was also detected in DOCA-salt hypertensive rats. Together, our study identifies BDNF as a candidate molecular mediator of activity-dependent changes at baroafferent synapses during hypertension. PMID:23172808

  1. Pitch Characteristics Before Ulnar Collateral Ligament Reconstruction in Major League Pitchers Compared With Age-Matched Controls

    PubMed Central

    Prodromo, John; Patel, Nimit; Kumar, Neil; Denehy, Kevin; Tabb, Loni Philip; Tom, James

    2016-01-01

    Background: Ulnar collateral ligament reconstruction (UCLR) is commonly performed in Major League Baseball (MLB) pitchers, but little is known about the preoperative pitch type and velocity characteristics of pitchers who go on to undergo UCLR. Hypothesis: Pitchers who required UCLR have thrown a greater percentage of fastballs and have greater pitch velocities compared with age-matched controls in the season before injury. Study Design: Case-control study; Level of evidence, 3. Methods: MLB pitchers active during the 2002 to 2015 seasons were included. The UCLR group consisted of MLB pitchers who received UCLR between 2003 and 2015, utilizing the season before surgery (2002-2014) for analysis. The control group comprised age-matched controls of the same season. Players who pitched less than 20 innings in the season before surgery were excluded. Pitch types were recorded as percentage of total pitches thrown. Pitch velocities were recorded for each pitch type. Pitch type and pitch velocities during preoperative seasons for UCLR pitchers were compared with age-matched controls using univariate and multivariate models. Results: A total of 114 cases that went on to UCLR and 3780 controls were included in the study. Pitchers who went on to UCLR appear to have greater fastball, slider, curveball, changeup, and split-fingered fastball velocities; there were no significant differences in pitch selection between the 2 groups. Conclusion: In the season before surgery, MLB pitchers who underwent UCLR demonstrated greater fastball, slider, curveball, changeup, and split-fingered fastball velocities, with no significant difference in pitch type. PMID:27350954

  2. Role of Complement 3a in the Synthetic Phenotype and Angiotensin II-Production in Vascular Smooth Muscle Cells From Spontaneously Hypertensive Rats

    PubMed Central

    Han, Ying; Fukuda, Noboru; Ueno, Takahiro; Endo, Morito; Ikeda, Kazuya; Xueli, Zhou; Matsumoto, Taro; Soma, Masayoshi; Matsumoto, Koichi

    2012-01-01

    Background Spontaneously hypertensive rats (SHR)-derived vascular smooth muscle cells (VSMCs) show exaggerated growth with a synthetic phenotype and angiotensin II (Ang II)-production. To evaluate the contribution of complement 3 (C3) or C3a toward these abnormalities in SHR, we examined effects of a C3a receptor inhibitor on proliferation, phenotype, and Ang II-production in VSMCs from SHR and Wistar–Kyoto (WKY) rats. Methods Expression of pre-pro-C3 messenger RNA (mRNA) and C3 protein was evaluated by reverse transcription-PCR and western blot analyses, and C3a receptor mRNA was evaluated by reverse transcription-PCR analysis in quiescent VSMCs from SHR and WKY rats. We examined the effects of the C3a inhibitor, SB290157, on proliferation and the expression of phenotype-marker and Krueppel-like factor 5 (KLF-5) mRNAs in VSMCs from SHR and WKY rats. We examined effects of C3a receptor inhibitor, SB290157, on Ang II-production in conditioned medium of VSMCs from SHR and WKY rats by a radioimmunoassay. Results Expression of pre-pro-C3 mRNA and C3 protein was significantly higher in SHR VSMCs than WKY VSMCs. SB290157 significantly inhibited proliferation of VSMCs from SHR, but not in cells from WKY rats. Relative to WKY VSMCs, SB290157 significantly increased the low expression of SM22α mRNA and decreased the high expression of osteopontin mRNA in SHR VSMCs. SB290157 significantly decreased the high expression of KLF-5 and Ang II-production in VSMCs from SHR, but not in cells from WKY rats. Conclusions C3a induces exaggerated growth, a synthetic phenotype and Ang II-production in SHR-derived VSMCs. C3a may be primarily involved in cardiovascular remodeling in hypertension. PMID:22089112

  3. Avoidance as expectancy in rats: sex and strain differences in acquisition

    PubMed Central

    Avcu, Pelin; Jiao, Xilu; Myers, Catherine E.; Beck, Kevin D.; Pang, Kevin C. H.; Servatius, Richard J.

    2014-01-01

    Avoidance is a core feature of anxiety disorders and factors which increase avoidance expression or its resistance represent a source of vulnerability for anxiety disorders. Outbred female Sprague Dawley (SD) rats and inbred male and female Wistar-Kyoto (WKY) rats expressing behaviorally inhibited (BI) temperament learn avoidance faster than male SD rats. The training protocol used in these studies had a longstanding interpretive flaw: a lever-press had two outcomes, termination of the warning signal (WS) and prevention of foot shock. To disambiguate between these two explanations, we conducted an experiment in which: (a) a lever-press terminated the WS and prevented shock, and (b) a lever-press only prevented shock, but did not influence the duration of the WS. Thus, a 2 × 2 × 2 (Strain × Sex × Training) design was employed to assess the degree to which the response contingency of the WS termination influenced acquisition. Male and female SD and WKY rats were matched on acoustic startle reactivity within strain and sex and randomly assigned to the training procedures. In addition, we assessed whether the degree of avoidance acquisition affected estrus cycling in female rats. Consistent with earlier work, avoidance performance of female rats was generally superior to males and WKY rats were superior to SD rats. Moreover, female SD and male WKY rats were roughly equivalent. Female sex and BI temperament were confirmed as vulnerability factors in faster acquisition of avoidance behavior. Avoidance acquisition disrupted estrus cycling with female WKY rats recovering faster than female SD rats. Although termination of the WS appears to be reinforcing, male and female WKY rats still achieved a high degree (greater than 80% asymptotic performance) of avoidance in the absence of the WS termination contingency. Such disambiguation will facilitate determination of the neurobiological basis for avoidance learning and its extinction. PMID:25339874

  4. Uteroplacental insufficiency programmes vascular dysfunction in non-pregnant rats: compensatory adaptations in pregnancy.

    PubMed

    Mazzuca, Marc Q; Tare, Marianne; Parkington, Helena C; Dragomir, Nicoleta M; Parry, Laura J; Wlodek, Mary E

    2012-07-15

    Intrauterine growth restriction is a risk factor for cardiovascular disease in adulthood. We have previously shown that intrauterine growth restriction caused by uteroplacental insufficiency programmes uterine vascular dysfunction and increased arterial stiffness in adult female rat offspring. The aim of this study was to investigate vascular adaptations in growth restricted female offspring when they in turn become pregnant. Uteroplacental insufficiency was induced in WKY rats by bilateral uterine vessel ligation (Restricted) or sham surgery (Control) on day 18 of pregnancy. F0 pregnant females delivered naturally at term. F1 Control and Restricted offspring were mated at 4 months of age and studied on day 20 of pregnancy. Age-matched non-pregnant F1 Control and Restricted females were also studied. Wire and pressure myography were used to test endothelial and smooth muscle function, and passive mechanical wall properties, respectively, in uterine, mesenteric, renal and femoral arteries of all four groups. Collagen and elastin fibres were quantified using polarized light microscopy and qRT-PCR. F1 Restricted females were born 10–15% lighter than Controls (P <0.05). Non-pregnant Restricted females had increased uterine and renal artery stiffness compared with Controls (P <0.05), but this difference was abolished at day 20 of pregnancy. Vascular smooth muscle and endothelial function were preserved in all arteries of non-pregnant and pregnant Restricted rats. Collagen and elastin content were unaltered in uterine arteries of Restricted females. Growth restricted females develop compensatory vascular changes during late pregnancy, such that region-specific vascular deficits observed in the non-pregnant state did not persist in late pregnancy. PMID:22586217

  5. Functional evidence of α1D-adrenoceptors in the vasculature of young and adult spontaneously hypertensive rats

    PubMed Central

    Villalobos-Molina, Rafael; López-Guerrero, J Javier; Ibarra, Maximiliano

    1999-01-01

    The role of α1D-adrenoceptors in the vasculature of spontaneously hypertensive (SHR) and normotensive Wistar Kyoto rats (WKY), of different ages was assessed in pithed rats by the use of the selective α1D-adrenoceptor antagonist BMY 7378 (8-[2-[4-(2-methoxyphenyl)-1-piperazinyl]-ethyl]-8-azaspiro [4.5]decane-7,9-dione dihydrochloride). BMY 7378 displaced the pressor effect of phenylephrine in young pre-hypertensive pithed SHR rats, but produced no effect in young WKY rats (dose ratio of 3.4 and 1.6, respectively), while in adult rats BMY 7378 produced a greater shift in the phenylephrine response curve than in younger animals (dose ratio of 3.2 and 6.2 in WKY and SHR, respectively). The presence of α1D-adrenoceptors in the vasculature of pre-hypertensive rats, suggests its role in the pathogenesis/maintenance of increased blood pressure. PMID:10323583

  6. Functional evidence of alpha1D-adrenoceptors in the vasculature of young and adult spontaneously hypertensive rats.

    PubMed

    Villalobos-Molina, R; López-Guerrero, J J; Ibarra, M

    1999-04-01

    The role of alpha1D-adrenoceptors in the vasculature of spontaneously hypertensive (SHR) and normotensive Wistar Kyoto rats (WKY), of different ages was assessed in pithed rats by the use of the selective alpha1D-adrenoceptor antagonist BMY 7378 (8-[2-[4-(2-methoxyphenyl)-1-piperazinyl]-ethyl]-8-azaspiro [4.5]decane-7,9-dione dihydrochloride). BMY 7378 displaced the pressor effect of phenylephrine in young pre-hypertensive pithed SHR rats, but produced no effect in young WKY rats (dose ratio of 3.4 and 1.6, respectively), while in adult rats BMY 7378 produced a greater shift in the phenylephrine response curve than in younger animals (dose ratio of 3.2 and 6.2 in WKY and SHR, respectively). The presence of alpha1D-adrenoceptors in the vasculature of pre-hypertensive rats, suggests its role in the pathogenesis/maintenance of increased blood pressure. PMID:10323583

  7. ACE inhibition reduces infarction in normotensive but not hypertensive rats: correlation with cortical ACE activity

    PubMed Central

    Porritt, Michelle J; Chen, Michelle; Rewell, Sarah S J; Dean, Rachael G; Burrell, Louise M; Howells, David W

    2010-01-01

    Angiotensin-converting enzyme (ACE) inhibition can reduce stroke risk by up to 43% in humans and reduce the associated disability, and hence understanding the mechanism of improvement is important. In animals and humans, these effects may be independent of the blood pressure-lowering effects of ACE inhibition. Normotensive (Wistar–Kyoto (WKY)) and hypertensive (spontaneously hypertensive rat (SHR)) animals were treated with the ACE inhibitors ramipril or lisinopril for 7 or 42 days before 2 hours of transient middle cerebral artery occlusion (MCAo). Blood pressure, serum ACE, and blood glucose levels were measured and stroke infarct volume was recorded 24 hours after stroke. Despite greater reductions in blood pressure, infarct size was not improved by ACE inhibition in hypertensive animals. Short-term ACE inhibition produced only a modest reduction in blood pressure, but WKY rats showed marked reductions in infarct volume. Long-term ACE inhibition had additional reductions in blood pressure; however, infarct volumes in WKY rats did not improve further but worsened. WKY rats differed from SHR in having marked cortical ACE activity that was highly sensitive to ACE inhibition. The beneficial effects of ACE inhibition on infarct volume in normotensive rats do not correlate with changes in blood pressure. However, WKY rats have ACE inhibitor-sensitive cortical ACE activity that is lacking in the SHR. PMID:20407464

  8. Stigmasterol reduces plasma cholesterol levels and inhibits hepatic synthesis and intestinal absorption in the rat.

    PubMed

    Batta, Ashok K; Xu, Guorong; Honda, Akira; Miyazaki, Teruo; Salen, Gerald

    2006-03-01

    Plant sterols compete with cholesterol (cholest-5-en-3beta-ol) for intestinal absorption to limit absorption and lower plasma concentrations of cholesterol. Stigmasterol (24-ethyl-cholesta-5,22-dien-3beta-ol; Delta(22) derivative of sitosterol [24-ethyl-cholest-5-en-3beta-ol]), but not campesterol (24-methyl-cholest-5-en-3beta-ol) and sitosterol, is reported to inhibit cholesterol biosynthesis via inhibition of sterol Delta(24)-reductase in human Caco-2 and HL-60 cell lines. We studied the effect of feeding 0.5% stigmasterol on plasma and liver sterols and intestinal cholesterol and sitosterol absorption in 12 wild-type Kyoto (WKY) and 12 Wistar rats. After 3 weeks of feeding, cholesterol and sitosterol absorption was determined in 6 rats from each group by plasma dual-isotope ratio method. After 3 more weeks, plasma and hepatic sterols and hepatic enzyme activities were determined in all rats. After feeding stigmasterol, baseline plasma cholesterol was 1.3 times and plant sterols 3 times greater in WKY compared with Wistar rats. Stigmasterol feeding lowered plasma cholesterol by approximately 11%, whereas plasma campesterol and sitosterol levels were virtually unchanged in both rat strains, and stigmasterol constituted 3.2% of plasma sterols in WKY rats and 1% in Wistar rats. After 6 weeks of feeding, cholesterol and sitosterol absorption decreased 23% and 30%, respectively, in WKY, and 22% and 16%, respectively, in the Wistar rats as compared with untreated rats. The intestinal bacteria in both rat strains metabolized stigmasterol to mainly the 5beta-H stanol (>40%), with only small amounts of 5alpha-H derivative (approximately 1.5%), whereas the C-22 double bond was resistant to bacterial metabolism. Hepatic stigmasterol levels increased from 11 microg/g liver tissue to 104 mug/g in WKY rats and from 5 microg/g liver tissue to 21 microg/g in Wistar rats. 3-Hydroxy-3-methylglutaryl coenzyme A reductase activity was suppressed 4-fold in the WKY and almost 1.8-fold

  9. Molecular basis for impaired collateral artery growth in the spontaneously hypertensive rat: insight from microarray analysis

    PubMed Central

    Unthank, Joseph L; McClintick, Jeanette N; Labarrere, Carlos A; Li, Lang; DiStasi, Matthew R; Miller, Steven J

    2013-01-01

    Analysis of global gene expression in mesenteric control and collateral arteries was used to investigate potential molecules, pathways, and mechanisms responsible for impaired collateral growth in the Spontaneously Hypertensive Rat (SHR). A fundamental difference was observed in overall gene expression pattern in SHR versus Wistar Kyoto (WKY) collaterals; only 6% of genes altered in collaterals were similar between rat strains. Ingenuity® Pathway Analysis (IPA) identified major differences between WKY and SHR in networks and biological functions related to cell growth and proliferation and gene expression. In SHR control arteries, several mechano-sensitive and redox-dependent transcription regulators were downregulated including JUN (−5.2×, P = 0.02), EGR1 (−4.1×, P = 0.01), and NFĸB1 (−1.95×, P = 0.04). Predicted binding sites for NFĸB and AP-1 were present in genes altered in WKY but not SHR collaterals. Immunostaining showed increased NFĸB nuclear translocation in collateral arteries of WKY and apocynin-treated SHR, but not in untreated SHR. siRNA for the p65 subunit suppressed collateral growth in WKY, confirming a functional role of NFkB. Canonical pathways identified by IPA in WKY but not SHR included nitric oxide and renin–angiotensin system signaling. The angiotensin type 1 receptor (AGTR1) exhibited upregulation in WKY collaterals, but downregulation in SHR; pharmacological blockade of AGTR1 with losartan prevented collateral luminal expansion in WKY. Together, these results suggest that collateral growth impairment results from an abnormality in a fundamental regulatory mechanism that occurs at a level between signal transduction and gene transcription and implicate redox-dependent modulation of mechano-sensitive transcription factors such as NFĸB as a potential mechanism. PMID:24303120

  10. Genetically determined differences in noradrenergic function: The spontaneously hypertensive rat model.

    PubMed

    Sterley, Toni-Lee; Howells, Fleur M; Russell, Vivienne A

    2016-06-15

    While genetic predisposition is a major factor, it is not known how development of attention-deficit/hyperactivity disorder (ADHD) is modulated by early life stress. The spontaneously hypertensive rat (SHR) displays the behavioral characteristics of ADHD (poorly sustained attention, impulsivity, hyperactivity) and is the most widely studied genetic model of ADHD. We have previously shown that SHR have disturbances in the noradrenergic system and that the early life stress of maternal separation failed to produce anxiety-like behavior in SHR, contrary to control Sprague-Dawley and Wistar-Kyoto (WKY) who showed typical anxiety-like behavior in later life. In the present study we investigated the effect of maternal separation on approach behavior (response to a novel object in a familiar environment) in preadolescent SHR and WKY. We also investigated whether maternal separation altered GABAA and NMDA receptor-mediated regulation of norepinephrine release in preadolescent SHR and WKY hippocampus. We found that female SHR, similar to male SHR, exhibited greater exploratory activity than WKY. Maternal separation significantly increased GABAA receptor-mediated inhibition of glutamate-stimulated release of norepinephrine in male and female SHR hippocampus but had no significant effect in WKY. Maternal separation had opposite effects on NMDA receptor-mediated inhibition of norepinephrine release in SHR and WKY hippocampus, as it increased inhibition of both glutamate-stimulated and depolarization-evoked release in SHR hippocampus but not in WKY. The results of the present study show that noradrenergic function is similarly altered by the early life stress of maternal separation in male and female SHR, while GABA- and glutamate-regulation of norepinephrine release remained unaffected by maternal separation in the control, WKY, rat strain. This article is part of a Special Issue entitled SI: Noradrenergic System. PMID:26612520

  11. Upregulation of renal and vascular nitric oxide synthase in young spontaneously hypertensive rats.

    PubMed

    Vaziri, N D; Ni, Z; Oveisi, F

    1998-06-01

    The available data on the role of the L-arginine/nitric oxide (NO) pathway in the genesis of hypertension in spontaneously hypertensive rats (SHR) are limited and contradictory. In an attempt to address this issue, male SHR were studied during the early phase of evolution of hypertension (age 8 to 12 weeks) to distinguish the primary changes of NO metabolism from those caused by advanced hypertension, vasculopathy, and aging late in the course of the disease. A group of age-matched male Wistar-Kyoto rats (WKY) served as controls. The SHR exhibited a marked rise in arterial blood pressure and a significant increase in urinary excretion and plasma concentration of NO metabolites (nitrite/nitrate [NOx]). Likewise, the SHR showed a significant elevation of thoracic aorta NO synthase (NOS) activity coupled with significant increases of kidney, aorta, inducible NOS (iNOS), and endothelial NOS (eNOS) proteins. In an attempt to determine whether the enhanced L-arginine/NO pathway is a consequence of hypertension, studies were repeated using 3-week-old animals before the onset of hypertension. The study revealed significant increases in urinary NOx excretion as well as vascular eNOS and renal iNOS proteins. In conclusion, the L-arginine/NO pathway is upregulated in young SHR both before and after the onset of hypertension. Thus, development of hypertension is not due to a primary impairment of NO production in SHR. On the contrary, NO production is increased in young SHR both before and after the onset of hypertension. PMID:9622137

  12. /sup 22/Na+ and /sup 86/Rb+ transport in vascular smooth muscle of SHR, Wistar Kyoto, and Wistar rats

    SciTech Connect

    Kuriyama, S.; Denny, T.N.; Aviv, A.

    1988-06-01

    To gain further insight into differences in cellular Na+ and K+ regulation between the spontaneously hypertensive rat (SHR), Wistar Kyoto (WKY), and American Wistar (W) rats, 22Na+ and 86Rb+ washouts were performed under steady-state conditions in cultured vascular smooth muscle cells from the three rat strains. SHR vascular smooth muscle cells showed significantly higher bumetanide sensitive 86Rb+ washout rate constant (x 10(-4)/min; mean +/- SEM) than WKY cells (-38.6 +/- 2.84 and -23.8 +/- 3.58, respectively; p less than 0.005). SHR vascular smooth muscle cells also exhibited significantly higher values than WKY cells in the total 22Na+ washout rate constant (x 10(-2)/min) (-61.0 +/- 1.57 vs. -53.8 +/- 1.24; p less than 0.005). The amiloride sensitive component of the 22Na+ washout rate constant accounted for these differences (-18.6 +/- 1.04 for SHR and -12.1 +/- 2.00 for WKY; p less than 0.05). There were no apparent differences in cellular Na+ concentrations between WKY and SHR cells. In general, the 86Rb+ and 22Na+ washout parameters of W rat cells were quite similar to those of cells from SHR. We conclude that the bumetanide-sensitive 86Rb+ washout (the Na+ K+-cotransport), the overall, and the amiloride-sensitive 22Na+ washout (the latter primarily represents the Na+/H+ antiport) are higher in SHR than WKY rat vascular smooth muscle cells. These findings indicate innate differences in cellular Na+ and K+ transport in vascular smooth muscle cells of the SHR and WKY rat. The mechanisms responsible for these differences are yet to be determined.

  13. Exposure to morphine-associated cues increases mu opioid receptor mRNA expression in the nucleus accumbens of Wistar Kyoto rats.

    PubMed

    Dennis, Torry S; Beck, Kevin D; Cominski, Tara P; Bobzean, Samara A M; Kuzhikandathil, Eldo V; Servatius, Richard J; Perrotti, Linda I

    2016-10-15

    The Wistar-Kyoto (WKY) rat has been proposed as a model of anxiety vulnerability as it exhibits pronounced behavioral inhibition, passive avoidance, exaggerated startle response, enhanced HPA-axis activation, and active avoidance that is resistant to extinction. Accumulating evidence suggests that WKY rats respond differently to rewarding stimuli when compared to outbred strains of rat. Conditioned responding to drug-associated cues is linked with alterations in the activation of mu opioid receptors (MOR) and kappa opioid receptors (KOR) in the nucleus accumbens (NAc). Furthermore, alterations in KOR expression/activation in the NAc of WKY rats are implicated in the regulation of some of the components that make up the unique behavioral phenotype of this strain. The purpose of this study was to extend upon previous work from our laboratory by investigating conditioned morphine reward in adult male WKY and SD rats, and to examine levels of KOR mRNA and MOR mRNA in the NAc at baseline and after acquisition of morphine CPP. Our results demonstrate that SD rats displayed morphine-induced CPP to each of the six doses of morphine tested (0.5, 1.25, 2.5, 5, 7.5, or 10mg/kg). Interestingly, WKY rats demonstrated CPP for only the 1.25, 2.5, and 5mg/kg doses, yet no preference at the lowest (0.5mg/kg) or highest (7.5 and 10mg/kg) doses. qPCR analysis of MOR and KOR in the NAc revealed no strain differences in basal levels of MOR, but higher levels of KOR in WKY rats compared to those of SD rats. Interestingly, after completion of the CPP task, WKY rats had overall higher levels of NAc MOR mRNA compared to SD rats; the initial basal differences in NAc KOR levels persisted without change due to CPP in either strain. These results demonstrate that the WKY rat exhibits a unique pattern of behavioral responding to morphine and implicates differences in NAc KOR signaling as a potential source of aversion to higher doses of morphine. Additionally, the CPP-induced upregulation of

  14. Comparison of serum sodium and potassium levels in patients with senile cataract and age-matched individuals without cataract

    PubMed Central

    Mathur, Gaurav; Pai, Vijaya

    2016-01-01

    Aim: The study was to analyze mean serum sodium and potassium levels in cataract patients and age-matched individuals without cataract. Methods and Materials: It was a prospective case-control study. Individuals more than 50 years of age who attended our ophthalmic center in the year 2007-2010 were grouped into those having cataract and those without cataract. Mean serum sodium and potassium levels in the cataract groups were calculated and compared with the control group. Statistical software SPSS14 was used for statistical analysis. Results: Mean serum sodium levels in cataract group was 135.1 meqv/l and 133 meqv/l in the control group. Mean potassium was 3.96 meqv/l in the case study group and 3.97 meqv/l in controls. Mean sodium levels among cases were significantly higher than control group. No difference was seen in the PSC group and control. The difference in mean potassium among the two groups was statistically insignificant. Conclusion: Diets with high sodium contents are a risk factor for senile cataract formation and dietary modifications can possibly reduce the rate of progression cataract. PMID:23552357

  15. Analysis of abstract and concrete word processing in persons with aphasia and age-matched neurologically healthy adults using fMRI.

    PubMed

    Sandberg, Chaleece; Kiran, Swathi

    2014-08-01

    The concreteness effect occurs in both normal and language-disordered populations. Research suggests that abstract and concrete concepts elicit differing neural activation patterns in healthy young adults, but this is undocumented in persons with aphasia (PWA). Three PWA and three age-matched controls were scanned using fMRI while processing abstract and concrete words. Consistent with current theories of abstract and concrete word processing, abstract words elicited activation in verbal areas, whereas concrete words additionally activated multimodal association areas. PWA show greater differences in neural activation than age-matched controls between abstract and concrete words, possibly due to an exaggerated concreteness effect. PMID:23548150

  16. Glomerulonephritis-induced changes in kidney gene expression in rats

    PubMed Central

    Pavkovic, Mira; Riefke, Björn; Frisk, Anna-Lena; Gröticke, Ina; Ellinger-Ziegelbauer, Heidrun

    2015-01-01

    We investigated a glomerulonephritis (GN) model in rats induced by nephrotoxic serum (NTS) which contains antibodies against the glomerular basement membrane (GBM). The anti-GBM GN model in rats is widely used since its biochemical and histopathological characteristics are similar to crescentic nephritis and Goodpasture's disease in humans (Pusey, 2003[2]). Male Wistar Kyoto (WKY) and Sprague–Dawley (SD) rats were dosed once with 1, 2.5 and 5 ml/kg nephrotoxic serum (NTS) or 1.5 and 5 ml/kg NTS, respectively. GN and tubular damage were observed histopathologically in all treated rats after 14 days. To obtain insight into molecular processes during GN pathogenesis, mRNA expression was investigated in WKY and SD kidneys using Affymetrix's GeneChip Rat genome 230_2.0 arrays (GSE64265). The immunopathological processes during GN are still not fully understood and likely involve both innate and adaptive immunity. In the present study, several hundred mRNAs were found deregulated, which functionally were mostly associated with inflammation and regeneration. The β-chain of the major histocompatibility complex class II RT1.B (Rt1-Bb) and complement component 6 (C6) were identified as two mRNAs differentially expressed between WKY and SD rat strains which could be related to known different susceptibilities to NTS of different rat strains; both were increased in WKY and decreased in SD rats (Pavkovic et al., 2015 [1]). Increased Rt1-Bb expression in WKY rats could indicate a stronger and more persistent cellular reaction of the adaptive immune system in this strain, in line with findings indicating adaptive immune reactions during GN. The complement cascade is also known to be essential for GN development, especially terminal cascade products like C6. PMID:26697341

  17. Strain differences in self-administration of methylphenidate and sucrose pellets in a rat model of attention-deficit hyperactivity disorder.

    PubMed

    Marusich, Julie A; McCuddy, William Travis; Beckmann, Joshua S; Gipson, Cassandra D; Bardo, Michael T

    2011-12-01

    Despite its abuse potential, methylphenidate (MPH) is widely prescribed for treatment of attention-deficit hyperactivity disorder (ADHD). The purpose of the present study was to examine MPH self-administration in a rat model of ADHD. Experiment 1 examined the acquisition of MPH self-administration and assessed the MPH dose-effect curve in spontaneously hypertensive rats (SHR), an inbred rat model of ADHD, Wistar Kyotos (WKY), the progenitor strain for SHR, and Sprague-Dawley (SD), an outbred control strain. Experiment 2 replicated Experiment 1, but replaced MPH infusions with sucrose pellets. Initial acquisition of MPH self-administration was greater in SHR and SD than WKY. However, with extended training using an incrementing fixed ratio schedule SHR and WKY did not differ in responding for MPH using the training dose (0.3 mg/kg/infusion) or other unit doses, except that SHR showed greater responding than WKY at 0.1 mg/kg/infusion. SHR also showed greater acquisition and maintenance of sucrose-reinforced responding compared with both WKY and SD. Greater initial acquisition of MPH self-administration in SHR than WKY may not be due to a strain-specific difference in sensitivity to the reinforcing effect of MPH. PMID:22015805

  18. Comparative antigen-induced gene expression profiles unveil novel aspects of susceptibility/resistance to adjuvant arthritis in rats.

    PubMed

    Yu, Hua; Lu, Changwan; Tan, Ming T; Moudgil, Kamal D

    2013-12-01

    Lewis (LEW) and Wistar Kyoto (WKY) rats of the same major histocompatibility complex (MHC) haplotype (RT.1(l)) display differential susceptibility to adjuvant-induced arthritis (AIA). LEW are susceptible while WKY are resistant to AIA. To gain insights into the mechanistic basis of these disparate outcomes, we compared the gene expression profiles of the draining lymph node cells (LNC) of these two rat strains early (day 7) following a potentially arthritogenic challenge. LNC were tested both ex vivo and after restimulation with the disease-related antigen, mycobacterial heat-shock protein 65. Biotin-labeled fragment cRNA was generated from RNA of LNC and then hybridized with an oligonucleotide-based DNA microarray chip. The differentially expressed genes (DEG) were compared by limiting the false discovery rate to <5% and fold change ≥2.0, and their association with quantitative trait loci (QTL) was analyzed. This analysis revealed overall a more active immune response in WKY than LEW rats. Important differences were observed in the association of DEG with QTL in LEW vs. WKY rats. Both the number of upregulated DEG associated with rat arthritis-QTL and their level of expression were relatively higher in LEW when compared to WKY rat; however, the number of downregulated DEG-associated with rat arthritis-QTL as well as AIA-QTL were found to be higher in WKY than in LEW rats. In conclusion, distinct gene expression profiles define arthritis-susceptible versus resistant phenotype of MHC-compatible inbred rats. These results would advance our understanding of the pathogenesis of autoimmune arthritis and might also offer potential novel targets for therapeutic purposes. PMID:23911410

  19. Single-port laparoscopic cholecystectomy vs standard laparoscopic cholecystectomy: A non-randomized, age-matched single center trial

    PubMed Central

    van der Linden, Yoen TK; Bosscha, Koop; Prins, Hubert A; Lips, Daniel J

    2015-01-01

    AIM: To compare the safety of single-port laparoscopic cholecystectomies with standard four-port cholecystectomies. METHODS: Between January 2011 and December 2012 datas were gathered from 100 consecutive patients who received a single-port cholecystectomy. Patient baseline characteristics of all 100 single-port cholecystectomies were collected (body mass index, age, etc.) in a database. This group was compared with 100 age-matched patients who underwent a conventional laparoscopic cholecystectomy in the same period. Retrospectively, per- and postoperative data were added. The two groups were compared to each other using independent t-tests and χ2-tests, P values below 0.05 were considered significantly different. RESULTS: No differences were found between both groups regarding baseline characteristics. Operating time was significantly shorter in the total single-port group (42 min vs 62 min, P < 0.05); in procedures performed by surgeons the same trend was seen (45 min vs 59 min, P < 0.05). Peroperative complications between both groups were equal (3 in the single-port group vs 5 in the multiport group; P = 0.42). Although not significant less postoperative complications were seen in the single-port group compared with the multiport group (3 vs 9; P = 0.07). No statistically significant differences were found between both groups with regard to length of hospital stay, readmissions and mortality. CONCLUSION: Single-port laparoscopic cholecystectomy has the potential to be a safe technique with a low complication rate, short in-hospital stay and comparable operating time. Single-port cholecystectomy provides the patient an almost non-visible scar while preserving optimal quality of surgery. Further prospective studies are needed to prove the safety of the single-port technique. PMID:26328034

  20. Avoidance expression in rats as a function of signal-shock interval: strain and sex differences

    PubMed Central

    Servatius, Richard J.; Avcu, Pelin; Ko, Nora; Jiao, Xilu; Beck, Kevin D.; Minor, Thomas R.; Pang, Kevin C. H.

    2015-01-01

    Inbred Wistar Kyoto (WKY) rats express inhibited temperament, increased sensitivity to stress, and exaggerated expressions of avoidance. A long-standing observation for lever press escape/avoidance learning in rats is the duration of the warning signal (WS) determines whether avoidance is expressed over escape. Outbred female Sprague-Dawley (SD) rats trained with a 10-s WS efficiently escaped, but failed to exhibit avoidance; avoidance was exhibited to a high degree with WSs longer than 20-s. We examined this longstanding WS duration function and extended it to male SD and male and female WKY rats. A cross-over design with two WS durations (10 or 60 s) was employed. Rats were trained (20 trials/session) in four phases: acquisition (10 sessions), extinction (10 sessions), re-acquisition (8 sessions) and re-extinction (8 sessions). Consistent with the literature, female and male SD rats failed to express avoidance to an appreciable degree with a 10-s WS. When these rats were switched to a 60-s WS, performance levels in the initial session of training resembled the peak performance of rats trained with a 60-s WS. Therefore, the avoidance relationship was acquired, but not expressed at 10-s WS. Further, poor avoidance at 10-s does not adversely affect expression at 60-s. Failure to express avoidance with a 10-s WS likely reflects contrasting reinforcement value of avoidance, not a reduction in the amount of time available to respond or competing responses. In contrast, WKY rats exhibited robust avoidance with a 10-s WS, which was most apparent in female WKY rats. Exaggerated expression of avoidances by WKY rats, especially female rats, further confirms this inbred strain as a model of anxiety vulnerability. PMID:26217200

  1. Avoidance expression in rats as a function of signal-shock interval: strain and sex differences.

    PubMed

    Servatius, Richard J; Avcu, Pelin; Ko, Nora; Jiao, Xilu; Beck, Kevin D; Minor, Thomas R; Pang, Kevin C H

    2015-01-01

    Inbred Wistar Kyoto (WKY) rats express inhibited temperament, increased sensitivity to stress, and exaggerated expressions of avoidance. A long-standing observation for lever press escape/avoidance learning in rats is the duration of the warning signal (WS) determines whether avoidance is expressed over escape. Outbred female Sprague-Dawley (SD) rats trained with a 10-s WS efficiently escaped, but failed to exhibit avoidance; avoidance was exhibited to a high degree with WSs longer than 20-s. We examined this longstanding WS duration function and extended it to male SD and male and female WKY rats. A cross-over design with two WS durations (10 or 60 s) was employed. Rats were trained (20 trials/session) in four phases: acquisition (10 sessions), extinction (10 sessions), re-acquisition (8 sessions) and re-extinction (8 sessions). Consistent with the literature, female and male SD rats failed to express avoidance to an appreciable degree with a 10-s WS. When these rats were switched to a 60-s WS, performance levels in the initial session of training resembled the peak performance of rats trained with a 60-s WS. Therefore, the avoidance relationship was acquired, but not expressed at 10-s WS. Further, poor avoidance at 10-s does not adversely affect expression at 60-s. Failure to express avoidance with a 10-s WS likely reflects contrasting reinforcement value of avoidance, not a reduction in the amount of time available to respond or competing responses. In contrast, WKY rats exhibited robust avoidance with a 10-s WS, which was most apparent in female WKY rats. Exaggerated expression of avoidances by WKY rats, especially female rats, further confirms this inbred strain as a model of anxiety vulnerability. PMID:26217200

  2. Effect of melatonin supplementation and cross-fostering on renal glutathione system and development of hypertension in spontaneously hypertensive rats.

    PubMed

    Siew-Keah, Lee; Sundaram, Arunkumar; Sirajudeen, K N S; Zakaria, Rahimah; Singh, H J

    2014-03-01

    Antenatal and postnatal environments are hypothesised to influence the development of hypertension. This study investigates the synergistic effect of cross-fostering and melatonin supplementation on the development of hypertension and renal glutathione system in spontaneously hypertensive rats (SHR). In one experiment, 1-day-old male SHR pups were fostered to either SHR (shr-SHR) or Wistar-Kyoto rats, (shr-WKY). In a concurrent experiment, SHR dams were given melatonin in drinking water (10 mg/kg body weight) from day 1 of pregnancy. Immediately following delivery, 1-day-old male pups were fostered either to SHR (Mel-shr-SHR) or WKY (Mel-shr-WKY) dams receiving melatonin supplementation until weaning on day 21. Upon weaning, melatonin supplementation was continued to these pups until the age of 16 weeks. Systolic blood pressures (SBP) were recorded at the age of 4, 6, 8, 12 and 16 weeks. Renal antioxidant activities were measured. Mean SBP of shr-WKY, Mel-shr-SHR and Mel-shr-WKY was significantly lower than that in shr-SHR until the age of 8 weeks. At 12 and 16 weeks of age, mean SBP of Mel-shr-WKY was lower than those in non-treated shr-SHR and shr-WKY pups but was not significantly different from that in Mel-shr-SHR. Renal glutathione peroxidase (GPx) and glutathione S-transferase (GST) activities were significantly higher in Mel-shr-SHR and Mel-shr-WKY at 16 weeks of age. It appears that combination of cross-fostering and melatonin supplementation exerts no synergistic effect on delaying the rise in blood pressure in SHR. The elevated GPx and GST activities are likely to be due to the effect of melatonin supplementation. PMID:23975651

  3. Repeated stress exposure causes strain-dependent shifts in the behavioral economics of cocaine in rats.

    PubMed

    Groblewski, Peter A; Zietz, Chad; Willuhn, Ingo; Phillips, Paul E M; Chavkin, Charles

    2015-03-01

    Cocaine-experienced Wistar and Wistar Kyoto (WKY) rats received four daily repeated forced swim stress sessions (R-FSS), each of which preceded 4-hour cocaine self-administration sessions. Twenty-four hours after the last swim stress, cocaine valuation was assessed during a single-session threshold procedure. Prior exposure to R-FSS significantly altered cocaine responding in Wistar, but not WKY, rats. Behavioral economic analysis of responding revealed that the Wistar rats that had received R-FSS exhibited an increase in the maximum price that they were willing to pay for cocaine (Pmax ). Pre-treatment with the long-lasting kappa opioid receptor (KOR) antagonist norbinaltorphimine prevented the stress-induced increase in Pmax . Thus, R-FSS exposure had strain-dependent effects on cocaine responding during the threshold procedure, and the stress effects on cocaine valuation exhibited by Wistar, but not WKY, required intact KOR signaling. PMID:24919534

  4. Repeated stress exposure causes strain-dependent shifts in the behavioral economics of cocaine in rats

    PubMed Central

    Groblewski, Peter A.; Zietz, Chad; Willuhn, Ingo; Phillips, Paul E. M.; Chavkin, Charles

    2015-01-01

    Cocaine-experienced Wistar and Wistar Kyoto (WKY) rats received four daily repeated forced swim stress sessions (R-FSS), each of which preceded 4-hour cocaine self-administration sessions. Twenty-four hours after the last swim stress, cocaine valuation was assessed during a single-session threshold procedure. Prior exposure to R-FSS significantly altered cocaine responding in Wistar, but not WKY, rats. Behavioral economic analysis of responding revealed that the Wistar rats that had received R-FSS exhibited an increase in the maximum price that they were willing to pay for cocaine (Pmax). Pre-treatment with the long-lasting kappa opioid receptor (KOR) antagonist norbinaltorphimine prevented the stress-induced increase in Pmax. Thus, R-FSS exposure had strain-dependent effects on cocaine responding during the threshold procedure, and the stress effects on cocaine valuation exhibited by Wistar, but not WKY, required intact KOR signaling. PMID:24919534

  5. Which oropharyngeal factors are significant risk factors for obstructive sleep apnea? An age-matched study and dentist perspectives

    PubMed Central

    Ruangsri, Supanigar; Jorns, Teekayu Plangkoon; Puasiri, Subin; Luecha, Thitisan; Chaithap, Chariya; Sawanyawisuth, Kittisak

    2016-01-01

    Objective Obstructive sleep apnea (OSA) is a common sleep breathing disorder. Untreated OSA may lead to a number of cardiovascular complications. Dentists may play an important role in OSA detection by conducting careful oral examinations. This study focused on the correlation of oral anatomical features in Thai patients who presented with OSA. Methods We conducted a prospective comparative study at a sleep/hypertension clinic and a dental clinic at Khon Kaen University in Thailand. Patients with OSA were enrolled in the study, along with age-matched patients with non-OSA (controls). Baseline characteristics, clinical data, and oropharyngeal data of all patients were compared between the two groups. Oropharyngeal measurements included tongue size, torus mandibularis, Mallampati classification, palatal space, and lateral pharyngeal wall area. Multivariate logistic regression analysis was used to identify the factors associated with OSA. Results During the study period, there were 156 patients who met the study criteria; 78 were patients with OSA and the other 78 were healthy control subjects. In the OSA group, there were 43 males with a mean age of 53 (standard deviation 12.29) years and a mean BMI of 30.86 kg/mm2. There were 37 males in the control group with a mean age of 50 (standard deviation 12.04) years and a mean BMI of 24.03 kg/mm2. According to multivariate logistic analysis, three factors were perfectly associated with OSA, including torus mandibularis class 6, narrow lateral pharyngeal wall, and Mallampati class 4. There were two other significant factors associated with having OSA, namely, BMI and Mallampati classification. The adjusted odds ratios (95% confidence interval) of these two factors were 1.445 (1.017, 2.052) and 5.040 (1.655, 15.358), respectively. Conclusion Dentists may play an important role in the detection of OSA in patients with high BMI through careful oropharyngeal examination in routine dental treatment. A large torus mandibularis

  6. Reduction in brain immunoreactive corticotropin-releasing factor (CRF) in spontaneously hypertensive rats

    SciTech Connect

    Hashimoto, K.; Hattori, T.; Murakami, K.; Suemaru, S.; Kawada, Y.; Kageyama, J.; Ota, Z.

    1985-02-18

    The brain CRF concentration of spontaneously hypertensive rats (SHR) and normotensive Wistar Kyoto rats (WKY) was examined by rat CRF radioimmunoassay. Anti-CRF serum was developed by immunizing rabbits with synthetic rat CRF. Synthetic rat CRF was also used as tracer and standard. The displacement of /sup 125/I-rat CRF by serially diluted extracts of male Wistar rats hypothalamus, thalamus, midbrain, pons, medulla oblongata, cerebral cortex, cerebellum and neurointermediate lobe was parallel to the displacement of synthetic rat CRF. In both WKY and SHR the highest levels of CRF immunoreactivity were shown by the hypothalamus and neurointermediate lobe, and considerable CRF immunoreactivity was also detected in other brain regions. The CRF immunoreactivity in the hypothalamus, neurointermediate lobe, midbrain, medulla oblongata and cerebral cortex was significantly reduced in SHR and it may suggest that CRF abnormality may be implicated in the reported abnormalities in the pituitary-adrenal axis, autonomic response and behavior of SHR.

  7. Evaluation of visual stress symptoms in age-matched dyslexic, Meares-Irlen syndrome and normal adults

    PubMed Central

    Alanazi, Mana A.; Alanazi, Saud A.; Osuagwu, Uchechukwu L.

    2016-01-01

    AIM To examine the prevalence of dyslexia and Meares-Irlen syndrome (MIS) among female students and determine their level of visual stress in comparison with normal subjects. METHODS A random sample of 450 female medical students of King Saud University Riyadh (age range, 18-30y) responded to a wide range of questions designed to accomplish the aims of this study. The detailed questionnaire consisted of 54 questions with 12 questions enquiring on ocular history and demography of participants while 42 questions were on visual symptoms. Items were categorized into critical and non-critical questions (CQ and NCQ) and were rated on four point Likert scale. Based on the responses obtained, the subjects were grouped into normal (control), dyslexic with or without MIS (Group 1) and subjects with MIS only (Group 2). Responses were analysed as averages and mean scores were calculated and compared between groups using one way analysis of variance to evaluate total visual stress score (TVSS=NCQ+CQ), critical and non-critical visual stress scores. The relationship between categorical variables such as age, handedness and condition were assessed with Chi-square test. RESULTS The completion rate was 97.6% and majority of the respondents (92%) were normal readers, 2% dyslexic and 6% had MIS. They were age-matched. More than half of the participants had visited an eye care practitioner in the last 2y. About 13% were recommended eye exercises and one participant experienced pattern glare. Hand preference was not associated with any condition but Group 1 subjects (3/9, 33%) were significantly more likely to be diagnosed of lazy eye than Group 2 (2/27, 7%) and control (27/414, 7%) subjects. The mean±SD of TVSS responses were 63±14 and it was 44±9 for CQ and 19±5 for NCQ. Responses from all three variables were normally distributed but the CQ responses were on the average more positive (82%) in Group 2 and less positive (46%) in Group 1 than control. With NCQ, the responses were

  8. Potassium channel antagonists and vascular reactivity in stroke-prone spontaneously hypertensive rats.

    PubMed

    Kolias, T J; Chai, S; Webb, R C

    1993-06-01

    The goal of this study was to characterize differences in contractile responsiveness to several potassium channel antagonists in vascular smooth muscle from stroke-prone spontaneously hypertensive rats (SHRSP) and Wistar-Kyoto normotensive rats (WKY). Helically-cut strips of carotid arteries (endothelium removed) from SHRSP and WKY were mounted in muscle baths for measurement of isometric force generation. Contractile responses to tetraethylammonium (10(-4) to 3 x 10(-2) mol/L) and barium (3 x 10(-5) mol/L), blockers of the voltage-dependent and large conductance, calcium activated potassium channels, were greater in carotid arteries from SHRSP than in those from WKY. In contrast, contractile responses to the voltage-dependent potassium channel blockers 3,4-diamino-pyridine (10(-6) to 3 x 10(-3) mol/L) and sparteine (10(-6) to 3 x 10(-2) mol/L) in arteries from SHRSP did not differ from WKY values. Carotid arteries from SHRSP and WKY did not contract to apamin (10(-9) to 10(-6) mol/L), an antagonist of the small conductance, calcium activated potassium channel. Furthermore, relaxation responses to diazoxide (3 x 10(-4) mol/L), an activator of the ATP-sensitive potassium channel, and subsequent contractions to the ATP-sensitive potassium channel blocker glyburide (10(-8) to 3 x 10(-6) mol/L) in arteries from SHRSP did not differ from WKY values. Carotid artery segments from SHRSP were more sensitive to the contractile effects of elevated potassium than those from WKY. We conclude that altered activity of the large conductance, calcium activated potassium channel may play a role in the increased responsiveness observed in arteries from SHRSP. PMID:8343237

  9. Characteristics of central binding sites for ( sup 3 H) DAMGO in spontaneously hypertensive rats

    SciTech Connect

    Gulati, A.; Bhargava, H.N. )

    1990-01-01

    The binding of ({sup 3}H) DAMGO, a highly selective ligand for {mu}-opiate receptors, to membranes of discrete brain regions and spinal cord of 10 week old spontaneously hypertensive (SHR) and normotensive Wistar-Kyoto (WKY) rats were determined. The brain regions examined were hypothalamus, amygdala, hippocampus, corpus striatum, pons and medulla, midbrain and cortex. ({sup 3}H) DAMGO bound to membranes of brain regions and spinal cord at a single high affinity site. The receptor density (B{sub max} value) and apparent dissociation constant (K{sub d} value) of ({sup 3}H) DAMGO to bind to membranes of hippocampus, corpus striatum, pons and medulla, cortex and spinal cord of WKY and SHR rats did not differ. The B{sub max} value of ({sup 3}H) DAMGO in membranes of hypothalamus and midbrain of SHR rats was significantly higher than in WKY rats but the K{sub d} values in the two strains did not differ. On the other hand, the B{sub max} value of ({sup 3}H) DAMGO in membranes of amygdala of SHR rats was lower than that of WKY rats but the K{sub d} values in the two strains were similar.

  10. Effects of AT1 receptor antagonism on kainate-induced seizures and concomitant changes in hippocampal extracellular noradrenaline, serotonin, and dopamine levels in Wistar-Kyoto and spontaneously hypertensive rats.

    PubMed

    Tchekalarova, Jana; Loyens, Ellen; Smolders, Ilse

    2015-05-01

    In the management of epilepsy, AT1 receptor antagonists have been suggested as an additional treatment strategy. A hyperactive brain angiotensin (Ang) II system and upregulated AT1 receptors are implicated in the cerebrovascular alterations in a genetic form of hypertension. Uncontrolled hypertension could also, in turn, be a risk factor for a seizure threshold decrease and development of epileptogenesis. The present study aimed to assess the effects of the selective AT1 receptor antagonist ZD7155 on kainic acid (KA)-induced status epilepticus (SE) development and accompanying changes in the hippocampal extracellular (EC) neurotransmitter levels of noradrenaline (NAD), serotonin (5-HT), and dopamine (DA) in spontaneously hypertensive rats (SHRs) and their parent strain Wistar-Kyoto (WKY) rats, since monoamines are well-known neurotransmitters involved in mechanisms of both epilepsy and hypertension. Status epilepticus was evoked in freely moving rats by a repetitive intraperitoneal (i.p.) administration of KA in subconvulsant doses. In the treatment group, ZD7155 (5mg/kg i.p.) was coadministered with the first KA injection. Spontaneously hypertensive rats exhibited higher susceptibility to SE than WKY rats, but the AT1 receptor antagonist did not alter the development of SE in SHRs or in WKY rats. In vivo microdialysis demonstrated significant KA-induced increases of the hippocampal NAD and DA levels in SHRs and of NAD, 5-HT, and DA in WKY rats. Although SHRs developed more severe seizures while receiving a lower dose of KA compared to WKY rats, AT1 receptor antagonism completely prevented all KA-induced increases of hippocampal monoamine levels in both rat strains without affecting seizure development per se. These results suggest a lack of direct relationship between KA-induced seizure susceptibility and adaptive changes of hippocampal NAD, 5-HT, and DA levels in the effects of ZD7155 in WKY rats and SHRs. PMID:25922088

  11. Multiple opiate receptors in the brain of spontaneously hypertensive rats

    SciTech Connect

    Das, S.; Bhargava, H.N.

    1986-03-01

    The characteristics of ..mu.., delta and kappa -opiate receptors in the brain of spontaneously hypertensive (SH) and normotensive Wistar-Kyoto (WKY) rats were determined using the receptor binding assays. The ligands used were /sup 3/H-naltrexone (..mu..), /sup 3/H-ethylketocyclazocine (EKC, kappa) and /sup 3/H-Tyr-D-Ser-Gly-Phe-Leu-Thr (DSTLE, delta). Since EKC binds to ..mu.. and delta receptors in addition to kappa, the binding was done in the presence of 100 nM each of DAGO and DADLE to suppress ..mu.. and delta sites, respectively. All three ligands bound to brain membranes of WKY rats at a single high affinity site with the following B/sub max/ (fmol/mg protein) and K/sub d/ (nM) values: /sup 3/H-naltrexone (130.5; 0.43) /sup 3/H-EKC (19.8, 1.7) and /sup 3/H-DSTLE (139, 2.5). The binding of /sup 3/H-naltrexone and /sup 3/H-DSTLE in the brain of WKY and SH did not differ. A consistent increase (22%) in B/sub max/ of /sup 3/H-EKC was found in SHR compared to WKY rats. However, the K/sub d/ values did not differ. The increase in B/sub max/ was due to increases in hypothalamus and cortex. It is concluded that SH rats have higher density of kappa-opiate receptors, particularly in hypothalamus and cortex, compared to WKY rats, and that kappa-opiate receptors may be involved in the pathophysiology of hypertension.

  12. Vascular reactivity in the spontaneously hypertensive stroke-prone rat. Effect of antihypertensive treatment.

    PubMed

    Soltis, E E; Bohr, D F

    1987-05-01

    This study investigated vascular responsiveness in stroke-prone spontaneously hypertensive rats (SHRSP) and the effect of antihypertensive treatment on this responsiveness. Weanling (4-week-old) male and female SHRSP and Wistar-Kyoto rats (WKY) received either the antihypertensive combination treatment of hydralazine plus hydrochlorothiazide in drinking water or tap water alone (controls) for 15 weeks. Whereas the antihypertensive combination prevented the development of hypertension in treated SHRSP (SHRSP-T), blood pressure remained unchanged in treated WKY (WKY-T). Femoral arterial smooth muscle responsiveness to KCl, norepinephrine, and calcium (in the presence of either 40 mM KCl or 1 microM norepinephrine) was not altered in SHRSP when compared with WKY. A significant increase in the sensitivity of femoral arteries to KCl and calcium (in the presence of 40 mM KCl) was seen, however, in SHRSP-T and WKY-T. An increased sensitivity to norepinephrine and calcium (in the presence of 1 microM norepinephrine) was seen only in SHRSP-T. Isoproterenol-induced relaxation was significantly attenuated in both SHRSP and SHRSP-T. Relaxation induced by sodium nitroprusside and calcium (membrane stabilization) was not different between the four groups. These results show that femoral arterial smooth muscle responsiveness to vasoconstrictor stimuli is not altered in SHRSP but that beta-adrenergic-mediated relaxation is attenuated. Antihypertensive treatment resulted in an enhanced responsiveness to these vasoconstrictor stimuli but had no effect on the relaxation properties of femoral arterial smooth muscle. PMID:3570424

  13. The effects of early-life predator stress on anxiety- and depression-like behaviors of adult rats.

    PubMed

    Chen, Lu-jing; Shen, Bing-qing; Liu, Dan-dan; Li, Sheng-tian

    2014-01-01

    Childhood emotional trauma contributes significantly to certain psychopathologies, such as post-traumatic stress disorder. In experimental animals, however, whether or not early-life stress results in behavioral abnormalities in adult animals still remains controversial. Here, we investigated both short-term and long-term changes of anxiety- and depression-like behaviors of Wistar rats after being exposed to chronic feral cat stress in juvenile ages. The 2-week predator stress decreased spontaneous activities immediately following stress but did not increase depression- or anxiety-like behaviors 4 weeks after the stimulation in adulthood. Instead, juvenile predator stress had some protective effects, though not very obvious, in adulthood. We also exposed genetic depression model rats, Wistar Kyoto (WKY) rats, to the same predator stress. In WKY rats, the same early-life predator stress did not enhance anxiety- or depression-like behaviors in both the short-term and long-term. However, the stressed WKY rats showed slightly reduced depression-like behaviors in adulthood. These results indicate that in both normal Wistar rats and WKY rats, early-life predator stress led to protective, rather than negative, effects in adulthood. PMID:24839560

  14. The Effects of Early-Life Predator Stress on Anxiety- and Depression-Like Behaviors of Adult Rats

    PubMed Central

    Chen, Lu-jing; Shen, Bing-qing; Liu, Dan-dan; Li, Sheng-tian

    2014-01-01

    Childhood emotional trauma contributes significantly to certain psychopathologies, such as post-traumatic stress disorder. In experimental animals, however, whether or not early-life stress results in behavioral abnormalities in adult animals still remains controversial. Here, we investigated both short-term and long-term changes of anxiety- and depression-like behaviors of Wistar rats after being exposed to chronic feral cat stress in juvenile ages. The 2-week predator stress decreased spontaneous activities immediately following stress but did not increase depression- or anxiety-like behaviors 4 weeks after the stimulation in adulthood. Instead, juvenile predator stress had some protective effects, though not very obvious, in adulthood. We also exposed genetic depression model rats, Wistar Kyoto (WKY) rats, to the same predator stress. In WKY rats, the same early-life predator stress did not enhance anxiety- or depression-like behaviors in both the short-term and long-term. However, the stressed WKY rats showed slightly reduced depression-like behaviors in adulthood. These results indicate that in both normal Wistar rats and WKY rats, early-life predator stress led to protective, rather than negative, effects in adulthood. PMID:24839560

  15. Different reactivity to angiotensin II of peripheral and renal arteries in spontaneously hypertensive rats: effect of acute and chronic angiotensin converting enzyme inhibition

    NASA Technical Reports Server (NTRS)

    Guidi, E.; Hollenberg, N. K.

    1986-01-01

    We assessed renal blood flow and pressor responses to graded angiotensin II doses in spontaneously hypertensive (SHR) and Wistar-Kyoto (WKY) rats ingesting a diet containing 1.6% sodium basally and after acute and chronic angiotensin converting enzyme (ACE) inhibition with captopril. In the basal state the pressor response to angiotensin II was enhanced (P<0.0005) and the renal vascular response was blunted (P<0.005) in SHR compared with WKY rats. After acute captopril administration the pressor response was enhanced in both strains, and the difference between them was maintained, while the renal vascular response was enhanced in both, but more in SHR, so that the renal vascular response in the SHR became larger than in WKY (P<0.0001). Chronic captopril treatment blunted both pressor and renal responses in WKY rats, but only the pressor response in SHR. The renal vessels of SHR seem to be different from those of WKY rats in reaction to exogenous angiotensin II, and in response to both acute administration of captopril (probably acting through blockade of angiotensin II production) and chronic administration of captopril (probably acting mainly through accumulation of kinin or production of prostaglandins).

  16. Interleukin-6 Modulates Colonic Transepithelial Ion Transport in the Stress-Sensitive Wistar Kyoto Rat

    PubMed Central

    O’Malley, Dervla; Dinan, Timothy G.; Cryan, John F.

    2012-01-01

    Immunological challenge stimulates secretion of the pro-inflammatory cytokine interleukin (IL)-6, resulting in variety of biological responses. In the gastrointestinal tract, IL-6 modulates the excitability of submucosal neurons and stimulates secretion into the colonic lumen. When considered in the context of the functional bowel disorder, irritable bowel syndrome (IBS), where plasma levels of IL-6 are elevated, this may reflect an important molecular mechanism contributing to symptom flares, particularly in the diarrhea-predominant phenotype. In these studies, colonic ion transport, an indicator of absorption and secretion, was assessed in the stress-sensitive Wistar Kyoto (WKY) rat model of IBS. Mucosa-submucosal colonic preparations from WKY and control Sprague Dawley (SD) rats were mounted in Ussing chambers and the basal short circuit current (ISC) was electrophysiologically recorded and compared between the strains. Exposure to IL-6 (1 nM) stimulated a secretory current of greater amplitude in WKY as compared to SD samples. Furthermore, the observed IL-6-mediated potentiation of secretory currents evoked by veratridine and capsaicin in SD rats was blunted in WKY rats. Exposure to IL-6 also stimulated an increase in transepithelial resistance in both SD and WKY colonic tissue. These studies demonstrate that the neuroexcitatory effects of IL-6 on submucosal plexi have functional consequences with alterations in both colonic secretory activity and permeability. The IL-6-induced increase in colonic secretory activity appears to neurally mediated. Thus, local increases in IL-6 levels and subsequent activation of enteric neurons may underlie alterations in absorpto-secretory function in the WKY model of IBS. PMID:23162465

  17. COMPARISON OF CARDIOPULMONARY RESPONSES OF WISTAR KYOTO (WKY) AND STROKE PRONE SPONTANEOUSLY HYPERTENSIVE RATS (SHRSP) TO PARTICULATE MATTER (PM) EXPOSURE

    EPA Science Inventory

    Although a clear link between cardiopulmonary disease and an increased susceptibility to air pollution has been established epidemiologically, the mechanistic link remains undefined. Animal models of disease are widely used to investigate this link. Here we compare the cardiopu...

  18. REPEATED TREATMENTS WITH DOXORUBICIN CAUSES ELECTROCARDIOGRAM (ECG) CHANGES AND INCREASED VENTRICULAR PREMATURE BEATS IN WISTAR-KYOTO (WKY) RATS

    EPA Science Inventory

    Doxorubicin (DOX) is a widely used anthracycline anti-neoplastic drug used to treat tumors. However it has been implicated in irreversible cardiac toxicity via the generation of a proxidant semiquinone free radical, which often results in cardiomyopathy and changes in the ECG. Ac...

  19. DIFFERENCES IN CARDIOVASCULAR RESPONSE TO PM EXPOSURE BETWEEN SPONTANEOUSLY HYPERTENSIVE STROKE-PRONE (SHSP) AND WISTAR-KYOTO (WKY) RATS.

    EPA Science Inventory

    ABSTRACT BODY: Epidemiological studies have shown that cardiovascular morbidity and mortality are associated with exposure to elevated levels of ambient particulate matter (PM), notably in people with pre-existing cardiopulmonary disease. To better understand the mechanisms of PM...

  20. SYSTEMIC TRANSLOCATION OF PARTICULATE MATTER (PM)-ASSOCIATED METALS FOLLOWING A SINGLE INTRATRACHEAL (IT) INSTILLATION IN WKY RATS

    EPA Science Inventory

    Ambient PM contains transition metals with differing water solubilities. Epidemiological studies show a link between PM exposure and an increased risk of cardiovascular disease. Direct translocation of PM-associated metals from the lung into systemic circulation may be partly res...

  1. Differentiating Glomerular Inflammation from Fibrosis in A Bone Marrow Chimera for Rat Anti-GBM Glomerulonephritis

    PubMed Central

    Zhou, Cindy; Lou, Kristie; Tatum, Kiana; Funk, Jeremiah; Wu, Jean; Bartkowiak, Todd; Kagan, David; Lou, Yahuan

    2015-01-01

    Background Many types of glomerulonephritis (GN) undergo tandem connected phases: inflammation and fibrosis. Fibrosis in human GNs leads to irreversible end stage disease. This study investigated how these two phases were controlled. Methods Using a rat anti-glomerular basement membrane (GBM) GN model, we established bone marrow (BM) chimeras between GN-resistant Lewis (LEW) and GN-susceptible Wistar Kyoto (WKY) rats. Glomerular inflammation and fibrosis were compared between chimeras. Results LEW’s BM to WKY (WKYLEW) chimeras with or without co-transfer of host WKY’s T cells were GN-resistant. On the other hand, WKY’s BM to LEW (LEWWKY) chimeras developed glomerular inflammation and albuminuria upon immunization. Quantitative analysis showed that the number and composition of inflammatory cells in glomeruli of immunized LEWWKY chimeras were similar to those in immunized WKY rats at their inflammatory peak. Thus, glomerular inflammation was controlled by BM derived non-T cell populations. However, unlike WKY rats, LEWWKY rats did not develop fibrosis until the end of experiments (84 days) in spite of persistent inflammation and albuminuria. Conclusion Inflammation alone was not sufficient to trigger fibrosis, suggesting a critical role of glomerular cells in the fibrotic process. As LEWWKY chimera allows us to separate glomerular inflammation from fibrosis, this model provides a useful tool to study how fibrosis is initiated following inflammation. PMID:26337665

  2. Differential ERK1/2 Signaling and Hypertrophic Response to Endothelin-1 in Cardiomyocytes from SHR and Wistar-Kyoto Rats: A Potential Target for Combination Therapy of Hypertension

    PubMed Central

    Zhu, Li-an; Fang, Ning-yuan; Gao, Ping-jin; Jin, Xian; Wang, Hai-ya; Liu, Zhenguo

    2015-01-01

    Extracellular signal regulated kinase½ (ERK1/2) signaling is critical to endothelin-1 (ET-1)-induced cardiomyocyte hypertrophy. This study was to investigate ERK1/2 signaling and hypertrophic response to ET-1 stimulation in cardiomyocytes (CMs) from spontaneous hypertensive rats (SHR) and normotensive Wistar-Kyoto rats (WKY). Primary neonatal SHR and WKY CMs were exposed to ET-1 for up to 24 hrs. Minimal basal ERK1/2 phosphorylation was present in WKY CMs, while a significant baseline ERK1/2 phosphorylation was observed in SHR CMs. ET-1 induced a time- and dose-dependent increase in ERK1/2 phosphorylation in both SHR and WKY CMs. However, ET-1-induced ERK1/2 activation occurred much earlier with significantly higher peak phosphorylation level, and stayed elevated for longer duration in SHR CMs than that in WKY CMs. ET-1-induced hypertrophic response was more prominent in SHR CMs than that in WKY CMs as reflected by increased cell surface area, intracellular actin density, and protein synthesis. Pre-treatment with ERK1/2 phosphorylation inhibitor PD98059 completely prevented ET-1-induced ERK1/2 phosphorylation and increases in cell surface area and protein synthesis in SHR and WKY CMs. The specific PI3 kinase inhibitor LY294002 blocked ET-1-induced Akt and ERK1/2 phosphorylation, and protein synthesis in CMs. These data indicated that ERK1/2 signaling was differentially enhanced in CMs, and was associated with increased cardiac hypertrophic response to ET-1 in SHR. ET-1-induced ERK1/2 activation and cardiac hypertrophy appeared to be mediated via PI3 kinase/Akt signaling in SHR and WKY. The differential ERK1/2 activation in SHR CMs by ET-1 might represent a potential target for combination therapy of hypertension. PMID:25360842

  3. Brain Injury After Intracerebral Hemorrhage in Spontaneously Hypertensive Rats

    PubMed Central

    Wu, Gang; Bao, Xuhui; Xi, Guohua; Keep, Richard; Thompson, B. Gregory; Hua, Ya

    2011-01-01

    Object Hypertension is the main cause of spontaneous intracerebral hemorrhages (ICH), but the effects of hypertension on ICH-induced brain injury have not been well studied. In this study, we examined ICH-induced brain injury in spontaneously hypertensive rats (SHR). Methods This two-part study was performed on 12 weeks old male SHR and Wistar Kyoto (WKY) rats. First, rats received an intracaudate injection of 0.3 units collagenase and hematoma sizes were determined at 24 hours. Second, rats were injected with 100-μL autologous whole blood into the right basal ganglia. Brain edema, neuronal death, ferritin expression, microglia activation, and neurological deficits were examined. Results Hematoma sizes were the same in SHR and WKY rats 24 hours after collagenase injection. SHR had greater neuronal death and neurological deficits after blood injection. ICH also resulted in higher brain ferritin levels and stronger activation of microglia in SHR. However, perihematomal brain edema was same in the SHR and WKY rats. Conclusion Moderate chronic hypertension resulted in more severe ICH-induced neuronal death and neurological deficits, but did not exaggerate hematoma enlargement and perihematomal brain edema in the rat ICH models. PMID:21294617

  4. The Spontaneously Hypertensive and Wistar Kyoto Rat Models of ADHD Exhibit Sub-Regional Differences in Dopamine Release and Uptake in the Striatum and Nucleus Accumbens

    PubMed Central

    Miller, Erin M.; Pomerleau, Francois; Huettl, Peter; Russell, Vivienne A.; Gerhardt, Greg A.; Glaser, Paul E.A.

    2012-01-01

    The most widely used animal model of attention-deficit/hyperactivity disorder (ADHD) is the spontaneously hypertensive rat (SHR/NCrl), which best represents the combined subtype (ADHD-C). Recent evidence has revealed that a progenitor strain, the Wistar Kyoto from Charles River Laboratories (WKY/NCrl), is useful as a model of the inattentive subtype (ADHD-PI) and the Wistar Kyoto from Harlan Laboratories (WKY/NHsd) and the Sprague Dawley (SD) have been suggested as controls. Dopamine (DA) dysfunction in the striatum (Str) and nucleus accumbens core (NAc) is thought to play a significant role in the pathophysiology of ADHD but data obtained with the SHR is equivocal. Using high-speed chronoamperometric recordings with carbon fiber microelectrodes, we found that the SHR/NCrl displayed decreased KCl-evoked DA release versus the WKY/NCrl model of ADHD-PI in the dorsal Str. The WKY/NCrl and the WKY/NHsd control did not differ from each other; however, the control SD released less DA than the WKY/NCrl model of ADHD-PI in the dorsal Str and less than the control WKY/NHsd in the intermediate Str. The SHR/NCrl had faster DA uptake in the ventral Str and NAc versus both control strains, while the WKY/NCrl model of ADHD-PI exhibited faster DA uptake in the NAc versus the SD control. These results suggest that increased surface expression of DA transporters may explain the more rapid uptake of DA in the Str and NAc of these rodent models of ADHD. PMID:22960443

  5. Effects of microwaves on three different strains of rats

    SciTech Connect

    Lu, S.T.; Lebda, N.A.; Lu, S.J.; Pettit, S.; Michaelson, S.M.

    1987-05-01

    Confounding factors influencing the sensitivity of biological indicators of microwave exposure--lethality, colonic temperature (Tco), decreased body mass (dW), corticosterone (CS), thyrotropin (TSH), thyroxine (T4), free thyroxine (FT4), and prolactin (PRL) concentration--were studied in Long-Evans (LE), Wistar-Kyoto (WKY), and spontaneous hypertensive (SHR) rats. The microwave signal was 2.45 GHz amplitude modulated at 120 Hz. Test power density ranged from 1 to 50 mW/cm2 for 2 h. In contrast to the LE and WKY rats, the SHR rats were characterized by intolerance (death) between 40 and 50 mW/cm2 (9.2 to 11.5 W/kg). The lowest lethal Tco was 41.1 degrees C. Survivors including all the LE and WKY rats were capable of maintaining Tco lower than 41.0 degrees C. In general, strain of rat seemed to influence other bioindicators and to interact with power density on these bioindicators. Except for Tco and PRL, baseline for the various bioindicators varied among the different strains of rats. Responses of T4 and FT4 were limited in magnitude and inconsistent among strains of rats. In general, the magnitude of Tco increase was more pronounced in SHR than in WKY. Differences between SHR and LE, however, could be noted only at 1, 10, and 50 mW/cm2. Increased Tco, increased magnitude of Dw, increased CS, decreased TSH, and increased PRL (stress reactions) could be noted in rats exposed to 30 mW/cm2 (approximately 6 W/kg) or higher, irrespective of strain.

  6. Defective dopamine-1 receptor adenylate cyclase coupling in the proximal convoluted tubule from the spontaneously hypertensive rat.

    PubMed Central

    Kinoshita, S; Sidhu, A; Felder, R A

    1989-01-01

    The natriuretic effect of DA-1 agonists is less in the spontaneously hypertensive rat (SHR) than its normotensive control, the Wistar-Kyoto rat (WKY). To determine a mechanism of the decreased effect of DA-1 agonists on sodium transport, DA-1 receptors in renal proximal convoluted tubule (PCT) were studied by radioligand binding and by adenylate cyclase (AC) determinations. Specific binding of 125I-SCH 23982 (defined by 10 microM SCH 23390, a DA-1 antagonist) was concentration dependent, saturable, and stereoselective. The dissociation constant, maximum receptor density, and DA-1 antagonist inhibition constant were similar in SHR and WKY. The apparent molecular weight of the DA-1 receptor determined by the photoaffinity D1 probe 125I-MAB was also similar in WKY and SHR. However, DA-1 agonists competed more effectively for specific 125I-SCH 23982 binding sites in WKY than in SHR. Basal as well as forskolin, parathyroid hormone, GTP and Gpp(NH)p-stimulated-AC activities were similar. In contrast DA-1 agonists (fenoldopam, SKF 38393, SND 911C12) stimulated AC activity to a lesser extent in SHR. GTP and Gpp(NH)p enhanced the ability of DA-1 agonists to stimulate AC activity in WKY but not in SHR. These data suggest a defect in the DA-1 receptor-second messenger coupling mechanism in the PCT of the SHR. Images PMID:2574187

  7. Magnetic Resonance Imaging Quantification of Regional Cerebral Blood Flow and Cerebrovascular Reactivity to Carbon Dioxide in Normotensive and Hypertensive Rats

    PubMed Central

    Leoni, Renata F.; Paiva, Fernando F.; Henning, Erica C.; Nascimento, George C.; Tannús, Alberto; de Araujo, Draulio B.; Silva, Afonso C.

    2011-01-01

    Hypertension afflicts 25% of the general population and over 50% of the elderly. In the present work, arterial spin labeling MRI was used to non-invasively quantify regional cerebral blood flow (CBF), cerebrovascular resistance and CO2 reactivity in spontaneously hypertensive rats (SHR) and in normotensive Wistar Kyoto rats (WKY), at two different ages (3 months and 10 months) and under the effects of two anesthetics, α-chloralose and 2% isoflurane (1.5 MAC). Repeated CBF measurements were highly consistent, differing by less than 10% and 18% within and across animals, respectively. Under α-chloralose, whole brain CBF at normocapnia did not differ between groups (young WKY: 61±3ml/100g/min; adult WKY: 62±4ml/100g/min; young SHR: 70±9ml/100g/min; adult SHR: 69±8ml/100g/min), indicating normal cerebral autoregulation in SHR. At hypercapnia, CBF values increased significantly, and a linear relationship between CBF and PaCO2 levels was observed. In contrast, 2% isoflurane impaired cerebral autoregulation. Whole brain CBF in SHR was significantly higher than in WKY rats at normocapnia (young SHR: 139±25ml/100g/min; adult SHR: 104±23ml/100g/min; young WKY: 55±9ml/100g/min; adult WKY: 71±19ml/100g/min). CBF values increased significantly with increasing CO2; however, there was a clear saturation of CBF at PaCO2 levels greater than 70 mmHg in both young and adult rats, regardless of absolute CBF values, suggesting that isoflurane interferes with the vasodilatory mechanisms of CO2. This behavior was observed for both cortical and subcortical structures. Under either anesthetic, CO2 reactivity values in adult SHR were decreased, confirming that hypertension, when combined with age, increases cerebrovascular resistance and reduces cerebrovascular compliance. PMID:21708273

  8. CARDIOVASCULAR AND THERMOREGULATORY RESPONSES OF UNRESTRAINED RATS EXPOSED TO FILTERED OR UNFILTERED DIESEL EXHAUST

    EPA Science Inventory

    Diesel exhaust (DE) has been associated with adverse cardiovascular and pulmonary health effects. The relative contributions of the gas-phase and particulate (PM) components of DE are less well understood. We exposed WKY rats with or without implanted radiotransmitters to air or ...

  9. Comparative gait analysis between children with autism and age-matched controls: analysis with temporal-spatial and foot pressure variables

    PubMed Central

    Lim, Bee-Oh; O’Sullivan, David; Choi, Bum-Gwon; Kim, Mi-Young

    2016-01-01

    [Purpose] The purpose of this study was to investigate the gait pattern of children with autism by using a gait analysis system. [Subjects] Thirty children were selected for this study: 15 with autism (age, 11.2 ± 2.8 years; weight, 48.1 ± 14.1 kg; height, 1.51 ± 0.11 m) and 15 healthy age-matched controls (age, 11.0 ± 2.9 years; weight, 43.6 ± 10 kg; height, 1.51 ± 0.011 m). [Methods] All participants walked three times on the GAITRite® system while their plantar pressure was being recorded. [Results] The results showed a reduction in cadence, gait velocity, and step length, and an increase in step width in children with autism. Plantar pressure variables highlight the differences between the active pressure areas, especially in the hindfoot of children with autism. [Conclusion] The results suggest that children with autism have an abnormal gait compared with that of age-matched controls, and thus they need extra attention to correct these abnormal gait patterns. PMID:26957776

  10. A Comparison of Substantia Nigra T1 Hyperintensity in Parkinson's Disease Dementia, Alzheimer's Disease and Age-Matched Controls: Volumetric Analysis of Neuromelanin Imaging

    PubMed Central

    Park, Ju-Yeon; Yun, Won-Sung; Jeon, Ji Yeong; Moon, Yeon Sil; Kim, Heejin; Kwak, Ki-Chang; Lee, Jong-Min; Han, Seol-Heui

    2016-01-01

    Objective Neuromelanin loss of substantia nigra (SN) can be visualized as a T1 signal reduction on T1-weighted high-resolution imaging. We investigated whether volumetric analysis of T1 hyperintensity for SN could be used to differentiate between Parkinson's disease dementia (PDD), Alzheimer's disease (AD) and age-matched controls. Materials and Methods This retrospective study enrolled 10 patients with PDD, 18 patients with AD, and 13 age-matched healthy elderly controls. MR imaging was performed at 3 tesla. To measure the T1 hyperintense area of SN, we obtained an axial thin section high-resolution T1-weighted fast spin echo sequence. The volumes of interest for the T1 hyperintense SN were drawn onto heavily T1-weighted FSE sequences through midbrain level, using the MIPAV software. The measurement differences were tested using the Kruskal-Wallis test followed by a post hoc comparison. Results A comparison of the three groups showed significant differences in terms of volume of T1 hyperintensity (p < 0.001, Bonferroni corrected). The volume of T1 hyperintensity was significantly lower in PDD than in AD and normal controls (p < 0.005, Bonferroni corrected). However, the volume of T1 hyperintensity was not different between AD and normal controls (p = 0.136, Bonferroni corrected). Conclusion The volumetric measurement of the T1 hyperintensity of SN can be an imaging marker for evaluating neuromelanin loss in neurodegenerative diseases and a differential in PDD and AD cases. PMID:27587951

  11. Enhanced 5-hydroxytryptamine (5-HT) release from vascular adrenergic nerves in spontaneously hypertensive rats

    SciTech Connect

    Kawasaki, H.; Urabe, M.; Takasaki, K.

    1986-03-01

    The release of 5-HT from vascular adrenergic nerves was compared between normotensive Wistar Kyoto rats (WKY) and SHR. The mesenteric vascular bed isolated from WKY and SHR was perfused with Krebs solution at a constant flow rate of 5 ml/min. Periarterial nerve stimulation (PNS) was delivered at 4 to 16 Hz for 30 sec. In the SHR preparation, the pressor response to PNS, previously decreased by prazonsin (50 nM), was greatly potentiated after treatment with 5-HT(1 ..mu..M) for 15 min and a frequency-dependent pressor response to PNS reappeared, whereas the 5-HT treatment did not alter the pressor response to exogenous norepinephrine (1 nmol) previously reduced by prazonsin. The potentiation of pressor response to PNS after 5-HT treatment was small in the WKY preparation. This potentiation in both WKY and SHR did not occur in the presence of ketanserin (10 nM). In the preparation labeled with (/sup 3/H)-5-HT, PNS (4-16 Hz) evoked a frequency-dependent increase of (/sup 3/H)-efflux, which was abolished by treatment with tetrodotoxin (100 nM) or 6-hydroxydopamine (50 mg/kg i.p. x 2) and in calcium-free Krebs solution. The PNS evoked-(/sup 3/H)-efflux was much greater in SHR than WKY. These results suggest that the release of 5-HT from vascular adrenergic nerves by PNS is enhanced in the SHR preparation.

  12. Opiate antagonist binding sites in discrete brain regions of spontaneously hypertensive and normotensive Wistar-Kyoto rats

    SciTech Connect

    Rahmani, N.H.; Gulati, A.; Bhargava, H.N. )

    1991-01-01

    The binding of {sup 3}H-naltrexone, an opiate receptor antagonist, to membranes of discrete brain regions and spinal cord of 10 week old spontaneously hypertensive (SHR) and normotensive Wistar-Kyoto (WKY) rats was determined. The brain regions examined were hypothalamus, amygdala, hippocampus, corpus striatum, pons and medulla, midbrain and cortex. {sup 3}H-Naltrexone bound to membranes of brain regions and spinal cord at a single high affinity site with an apparent dissociation constant value of 3 nM. The highest density of {sup 3}H-naltrexone binding sites were in hippocampus and lowest in the cerebral cortex. The receptor density (B{sub max}value) and apparent dissociation constant (K{sub d} value) values of {sup 3}H-naltrexone to bind to opiate receptors on the membranes of amygdala, hippocampus, corpus striatum, pons and medulla, midgrain, cortex and spinal cord of WKY and SHR rates did not differ. The B{sub max} value of {sup 3}H-naltrexone binding to membranes of hypothalamus of SHR rates was 518% higher than WKY rats but the K{sub d} values in the two strains did not differ. It is concluded that SHR rats have higher density of opiate receptors labeled with {sup 3}H-naltrexone in the hypothalamus only, in comparison with WKY rats, and that such a difference in the density of opiate receptors may be related to the elevated blood pressure in SHR rats.

  13. Disodium Cromoglycate Reverses Colonic Visceral Hypersensitivity and Influences Colonic Ion Transport in a Stress-Sensitive Rat Strain

    PubMed Central

    Carroll, Siobhan Yvonne; O’Mahony, Siobhain Mary; Grenham, Susan; Cryan, John Francis; Hyland, Niall Patrick

    2013-01-01

    The interface between psychiatry and stress-related gastrointestinal disorders (GI), such as irritable bowel syndrome (IBS), is well established, with anxiety and depression the most frequently occurring comorbid conditions. Moreover, stress-sensitive Wistar Kyoto (WKY) rats, which display anxiety- and depressive-like behaviors, exhibit GI disturbances akin to those observed in stress-related GI disorders. Additionally, there is mounting preclinical and clinical evidence implicating mast cells as significant contributors to the development of abdominal visceral pain in IBS. In this study we examined the effects of the rat connective tissue mast cell (CTMC) stabiliser, disodium cromoglycate (DSCG) on visceral hypersensitivity and colonic ion transport, and examined both colonic and peritoneal mast cells from stress-sensitive WKY rats. DSCG significantly decreased abdominal pain behaviors induced by colorectal distension in WKY animals independent of a reduction in colonic rat mast cell mediator release. We further demonstrated that mast cell-stimulated colonic ion transport was sensitive to inhibition by the mast cell stabiliser DSCG, an effect only observed in stress-sensitive rats. Moreover, CTMC-like mast cells were significantly increased in the colonic submucosa of WKY animals, and we observed a significant increase in the proportion of intermediate, or immature, peritoneal mast cells relative to control animals. Collectively our data further support a role for mast cells in the pathogenesis of stress-related GI disorders. PMID:24367692

  14. Disodium cromoglycate reverses colonic visceral hypersensitivity and influences colonic ion transport in a stress-sensitive rat strain.

    PubMed

    Carroll, Siobhan Yvonne; O'Mahony, Siobhain Mary; Grenham, Susan; Cryan, John Francis; Hyland, Niall Patrick

    2013-01-01

    The interface between psychiatry and stress-related gastrointestinal disorders (GI), such as irritable bowel syndrome (IBS), is well established, with anxiety and depression the most frequently occurring comorbid conditions. Moreover, stress-sensitive Wistar Kyoto (WKY) rats, which display anxiety- and depressive-like behaviors, exhibit GI disturbances akin to those observed in stress-related GI disorders. Additionally, there is mounting preclinical and clinical evidence implicating mast cells as significant contributors to the development of abdominal visceral pain in IBS. In this study we examined the effects of the rat connective tissue mast cell (CTMC) stabiliser, disodium cromoglycate (DSCG) on visceral hypersensitivity and colonic ion transport, and examined both colonic and peritoneal mast cells from stress-sensitive WKY rats. DSCG significantly decreased abdominal pain behaviors induced by colorectal distension in WKY animals independent of a reduction in colonic rat mast cell mediator release. We further demonstrated that mast cell-stimulated colonic ion transport was sensitive to inhibition by the mast cell stabiliser DSCG, an effect only observed in stress-sensitive rats. Moreover, CTMC-like mast cells were significantly increased in the colonic submucosa of WKY animals, and we observed a significant increase in the proportion of intermediate, or immature, peritoneal mast cells relative to control animals. Collectively our data further support a role for mast cells in the pathogenesis of stress-related GI disorders. PMID:24367692

  15. Endothelium-derived relaxing factor released by 5-HT: distinct from nitric oxide in basilar arteries of normotensive and hypertensive rats.

    PubMed Central

    Yokota, Y; Imaizumi, Y; Asano, M; Matsuda, T; Watanabe, M

    1994-01-01

    1. The role of the endothelium in cerebrovascular responses to 5-hydroxytryptamine (5-HT) was investigated in spontaneously hypertensive rats (SHR) and normotensive Wistar-Kyoto rats (WKY) in vitro. 2. Cumulative addition of 5-HT caused concentration-dependent contractions in ring preparations of SHR basilar arteries; the contractile response was smaller in WKY basilar arteries. 3. Removal of the endothelium enhanced markedly the contractile responses to 5-HT in WKY arteries but had only a slight effect in SHR arteries. The responsiveness to 5-HT in WKY arteries after removal of endothelium was comparable to that in SHR arteries. 4. The endothelium-dependent relaxation induced by acetylcholine in WKY basilar arteries was almost abolished by treatment with 10 microM methylene blue or 10 microM NG-nitro-L-arginine (L-NOARG). However, the response to 5-HT was not affected by treatment with methylene blue, L-NOARG or indomethacin. 5. Application of 10-20 mM K+ or 3.2 mM tetraethylammonium (TEA) did not change significantly, or only increased slightly, the resting tension, but markedly enhanced the contractile response to 5-HT in WKY arteries with endothelium. In contrast, the submaximal response to 5-HT in SHR arteries with endothelium was significantly enhanced by 0.3 mM TEA. 6. In the presence of 1 mM TEA, the application of 10 microM L-NOARG further enhanced the responses of 5-HT in WKY arteries with endothelium. In SHR arteries with endothelium, 10 microM L-NOARG per se enhanced slightly but significantly the responses to 5-HT.(ABSTRACT TRUNCATED AT 250 WORDS) PMID:7812628

  16. Malignant alterations following early blockade of nitric oxide synthase in hypertensive rats.

    PubMed

    Hsu, Yung Hsiang; Hsu, Bang Gee; Chen, Hsing I

    2007-12-31

    Nitric oxide (NO) is important for the homeostasis of organ functions. We studied the structural and functional changes in the cardiovascular (CV) and renal systems following early NO deprivation by various nonspecific and specific NO synthase (NOS) inhibitors: N-nitro-L-arginine methyl ester (L-NAME), N-nitro-L-arginine (L-NA), S-methyl-isothiourea (SMT), and L-N6-(1-iminoethyl)-lysine (L-Nil). The aim is to elucidate the involvement of NO through endothelial or inducible NOS (eNOS and iNOS). Drugs were given to spontaneously hypertensive rats (SHR) and age-matched normotensive Wistar Kyoto rats (WKY) from a young age (5-wk-old). Physiological, biochemical, and pathological examinations were performed. L-NAME and L-NA treatment caused a rapid increase in tail cuff pressure (TCP). The TCP of SHR reached a malignant level within 30 days with signs of stroke, proteinuria [corrected] severe glomerular sclerosis, and moderate ventricular hypertrophy (VH). The plasma nitrite/nitrate was reduced, while creatinine, urea nitrogen and uric acid were elevated. The renal tissue cyclic guanosine monophosphate (cGMP) was decreased with an elevated collagen content. The numbers of sclerotic glomeruli, arteriolar and glomerular injury scores were markedly increased, accompanied by reduction in renal blood flow, filtration rate, and fraction. Plasma endothelin-1 was increased following L,-NAME or L-NA treatment for 10 days. The expression of eNOS and iNOS mRNA was depressed by L-NAME and L-NA. The relevant iNOS inhibitors, SMT and L-Nil depressed the iNOS expression, but did not produce significant changes in CV and renal systems. The continuous release of NO via the eNOS system provides a compensatory mechanism to prevent the genetically hypertensive rats from rapid progression to malignant phase. Removal of this compensation results in VH, stroke, glomerular damage, renal function impairment, and sudden death. PMID:18442011

  17. Comparison of. beta. -adrenergic receptors between different strains of rat with different susceptibility to hypertension: a survey of binding characteristics, responsiveness and corticosteroid induced modulation

    SciTech Connect

    Jazayeri, A.

    1987-01-01

    The objective of this research was two fold: the first objective was to measure ..beta..-adrenergic receptor characteristics (Bmax and Kd) and responsiveness (isoproterenol induced c-AMP production) between different strains of rat with different susceptibility to hypertension. The second objective of this research was to determine if ..beta..-adrenergic receptors of arterial smooth muscle cells (ASMC) can be modulated by corticosteroids. These studies were done under controlled conditions using ASMC grown in culture from the rat aorta. (/sup 3/H)-dihydroalprenolol (DHA) was used to measure ..beta..-adrenergic receptor binding characteristics (Kd and Bmax). Scatchard analysis of (/sup 3/H)-DHA binding revealed one class of binding sites with affinity in the range of 100 pM. (/sup 3/H)-DHA binding comparison between Wistar-Kyoto (WKY) and spontaneously hypertensive rats (SHR) revealed that the Bmax for SHR was significantly lower than WKY. However, isoproterenol stimulated c-AMP production by SHR, is significantly higher than WKY. Fischer 344 rats, showed similar Bmax, Kd, and responsiveness as WKY rats. Dahl-sensitive and Dahl-resistant rats had equal Bmax and Kd measured by (/sup 3/H)-DHA binding.

  18. Transient Receptor Potential Channel Opening Releases Endogenous Acetylcholine, which Contributes to Endothelium-Dependent Relaxation Induced by Mild Hypothermia in Spontaneously Hypertensive Rat but Not Wistar-Kyoto Rat Arteries.

    PubMed

    Zou, Q; Leung, S W S; Vanhoutte, P M

    2015-08-01

    Mild hypothermia causes endothelium-dependent relaxations, which are reduced by the muscarinic receptor antagonist atropine. The present study investigated whether endothelial endogenous acetylcholine contributes to these relaxations. Aortic rings of spontaneously hypertensive rats (SHRs) and normotensive Wistar-Kyoto (WKY) rats were contracted with prostaglandin F2 α and exposed to progressive mild hypothermia (from 37 to 31°C). Hypothermia induced endothelium-dependent, Nω-nitro-l-arginine methyl ester-sensitive relaxations, which were reduced by atropine, but not by mecamylamine, in SHR but not in WKY rat aortae. The responses in SHR aortae were also reduced by acetylcholinesterase (the enzyme responsible for acetylcholine degradation), bromoacetylcholine (inhibitor of acetylcholine synthesis), hemicholinium-3 (inhibitor of choline uptake), and vesamicol (inhibitor of acetylcholine release). The mild hypothermia-induced relaxations in both SHR and WKY rat aortae were inhibited by AMTB [N-(3-aminopropyl)-2-[(3-methylphenyl)methoxy]-N-(2-thienylmethyl)-benzamide; the transient receptor potential (TRP) M8 inhibitor]; only those in SHR aortae were inhibited by HC-067047 [2-methyl-1-[3-(4-morpholinyl)propyl]-5-phenyl-N-[3-(trifluoromethyl)phenyl]-1H-pyrrole-3-carboxamide; TRPV4 antagonist] while those in WKY rat aortae were reduced by HC-030031 [2-(1,3-dimethyl-2,6-dioxo-1,2,3,6-tetrahydro-7H-purin-7-yl)-N-(4-isopropylphenyl)acetamide; TRPA1 antagonist]. The endothelial uptake of extracellular choline and release of cyclic guanosine monophosphate was enhanced by mild hypothermia and inhibited by HC-067047 in SHR but not in WKY rat aortae. Compared with WKY rats, the SHR preparations expressed similar levels of acetylcholinesterase and choline acetyltransferase, but a lesser amount of vesicular acetylcholine transporter, located mainly in the endothelium. Thus, mild hypothermia causes nitric oxide-dependent relaxations by opening TRPA1 channels in WKY rat aortae

  19. Sensorimotor Control of Tracking Movements at Various Speeds for Stroke Patients as Well as Age-Matched and Young Healthy Subjects

    PubMed Central

    Ao, Di; Song, Rong; Tong, Kai-yu

    2015-01-01

    There are aging- and stroke-induced changes on sensorimotor control in daily activities, but their mechanisms have not been well investigated. This study explored speed-, aging-, and stroke-induced changes on sensorimotor control. Eleven stroke patients (affected sides and unaffected sides) and 20 control subjects (10 young and 10 age-matched individuals) were enrolled to perform elbow tracking tasks using sinusoidal trajectories, which included 6 target speeds (15.7, 31.4, 47.1, 62.8, 78.5, and 94.2 deg/s). The actual elbow angle was recorded and displayed on a screen as visual feedback, and three indicators, the root mean square error (RMSE), normalized integrated jerk (NIJ) and integral of the power spectrum density of normalized speed (IPNS), were used to investigate the strategy of sensorimotor control. Both NIJ and IPNS had significant differences among the four groups (P<0.01), and the values were ranked in the following order: young controls < age-matched controls

  20. Intensively managed young children with type 1 diabetes consume high-fat, low-fiber diets similar to age-matched controls.

    PubMed

    Mehta, Sanjeev N; Volkening, Lisa K; Quinn, Nicolle; Laffel, Lori M B

    2014-05-01

    Despite significant emphasis on nutrition, older children with diabetes demonstrate poor dietary quality. We tested the hypothesis that dietary quality in young children with type 1 diabetes (T1D) would be better than age-matched children in the US population. Dietary data from children with T1D (n = 67) aged 2 to 12 years attending a pediatric diabetes clinic were compared with a nationally representative, age-matched sample from the National Health and Nutrition Examination Survey (NHANES; n = 1691). Multiple 24-hour dietary recalls were used. Recommended intakes were based on national guidelines, and dietary quality was assessed using the Healthy Eating Index-2005. More children with T1D were overweight or obese compared with children participating in NHANES (42% vs 30%, P = .04). Greater proportions of children with T1D met daily recommendations for vegetables (22% vs 13%, P = .03), whole grains (12% vs 5%, P = .005), and dairy (55% vs 36%, P = .001) compared with NHANES children, whereas similar proportions met daily fruit recommendations (40% vs 33%, P = .2). Less than one-third of all children limited total fat to recommended levels; children with T1D consumed more saturated fat than did NHANES children (14% vs 12% total energy intake, P = .0009). Fiber intakes were very low in both groups. Compared with NHANES children, children with T1D had higher Healthy Eating Index-2005 scores (59.6 vs 49.7, P = .0006) primarily because of lower intakes of added sugars. The nutritional intake of young children with T1D remains suboptimal in the contemporary era of diabetes management. Despite focused nutrition management, young children with T1D consume high-fat, low-fiber diets comparable with youth in the general population. PMID:24916556

  1. Secreted proteome profiling in human RPE cell cultures derived from donors with age related macular degeneration and age matched healthy donors.

    PubMed

    An, Eunkyung; Lu, Xiaoning; Flippin, Jessica; Devaney, Joseph M; Halligan, Brian; Hoffman, Eric P; Hoffman, Eric; Strunnikova, Nataly; Csaky, Karl; Hathout, Yetrib

    2006-10-01

    Age-related macular degeneration (AMD) is characterized by progressive loss of central vision, which is attributed to abnormal accumulation of macular deposits called "drusen" at the interface between the basal surface of the retinal pigment epithelium (RPE) and Bruch's membrane. In the most severe cases, drusen deposits are accompanied by the growth of new blood vessels that breach the RPE layer and invade photoreceptors. In this study, we hypothesized that RPE secreted proteins are responsible for drusen formation and choroidal neovascularization. We used stable isotope labeling by amino acids in cell culture (SILAC) in combination with LC-MS/MS analysis and ZoomQuant quantification to assess differential protein secretion by RPE cell cultures prepared from human autopsy eyes of AMD donors (diagnosed by histological examinations of the macula and genotyped for the Y402H-complement factor H variant) and age-matched healthy control donors. In general, RPE cells were found to secrete a variety of extracellular matrix proteins, complement factors, and protease inhibitors that have been reported to be major constituents of drusen (hallmark deposits in AMD). Interestingly, RPE cells from AMD donors secreted 2 to 3-fold more galectin 3 binding protein, fibronectin, clusterin, matrix metalloproteinase-2 and pigment epithelium derived factor than RPE cells from age-matched healthy donors. Conversely, secreted protein acidic and rich in cysteine (SPARC) was found to be down regulated by 2-fold in AMD RPE cells versus healthy RPE cells. Ingenuity pathway analysis grouped these differentially secreted proteins into two groups; those involved in tissue development and angiogenesis and those involved in complement regulation and protein aggregation such as clusterin. Overall, these data strongly suggest that RPE cells are involved in the biogenesis of drusen and the pathology of AMD. PMID:17022631

  2. Origin of the Y chromosome influences intrarenal vascular responsiveness to angiotensin I and angiotensin (1-7) in stroke-prone spontaneously hypertensive rats.

    PubMed

    Sampson, Amanda K; Andrews, Karen L; Graham, Delyth; McBride, Martin W; Head, Geoffrey A; Thomas, Merlin C; Chin-Dusting, Jaye P F; Dominiczak, Anna F; Jennings, Garry L

    2014-12-01

    The lineage of the Y chromosome accounts for up to 15 to 20 mm Hg in arterial pressure. Genes located on the Y chromosome from the spontaneously hypertensive rat (SHR) are associated with the renin-angiotensin system. Given the important role of the renin-angiotensin system in the renal regulation of fluid homeostasis and arterial pressure, we hypothesized that the origin of the Y chromosome influences arterial pressure via interaction between the intrarenal vasculature and the renin-angiotensin system. Sixteen-week-old normotensive rats (Wistar Kyoto [WKY]), spontaneously hypertensive stroke-prone rat (SHRSP), and 2 reciprocal Y consomic rat strains, 1 comprising the WKY autosomes and X chromosome with the Y chromosome from the hypertensive rat strain (WKY.SPGlaY) and vice versa (SP.WKYGlaY), were examined. SP.WKYGlaY had lower systolic blood pressure than SHRSP (195±5 versus 227±8 mm Hg; P<0.03), whereas WKY.SPGlaY had higher systolic blood pressure compared with WKY (157±3 versus 148±3 mm Hg; P<0.05), measured by radiotelemetry. Compared with WKY rats, SHRSP had higher plasma angiotensin(1-7) (Ang (1-7)):Ang II ratio (WKY: 0.13±0.01 versus SHRSP: 1.33±0.4; P<0.005), greater angiotensin II receptor type 2 and Mas receptor mRNA expression, and a blunted renal constrictor response to intrarenal Ang I and Ang(1-7) infusions. Introgression of the normotensive Y chromosome into the SHRSP background (SP.WKYGlaY) restored responses in the SHRSP to WKY levels, evidenced by a reduction in plasma Ang(1-7):Ang II ratio (SP.WKYGlaY: 0.24±0.02; P<0.01), angiotensin II receptor type 2, and Mas receptor mRNA expression and an increased vasoconstrictor response to intrarenal Ang I and Ang(1-7) infusion. This study demonstrates that the origin of the Y chromosome significantly impacts the renal vascular responsiveness and therefore may influence the long-term renal regulation of blood pressure. PMID:25201895

  3. Insulin resistance in SHR/NDmc-cp rats correlates with enlarged perivascular adipocytes and endothelial cell dysfunction in skeletal muscle.

    PubMed

    Hariya, Natsuyo; Mochizuki, Kazuki; Inoue, Seiya; Morioka, Kosuke; Shimada, Masaya; Okuda, Tohru; Goda, Toshinao

    2014-01-01

    Ectopic adipose tissue in skeletal muscle is implicated in the development of insulin resistance, which is frequently induced by abnormal dietary habits such as excessive eating and a high-fat diet. However, the characteristics of ectopic adipocytes are unknown. In this study, we investigated the characteristics of ectopic adipocytes in the skeletal muscle of spontaneously hypertensive corpulent congenic (SHR/NDmc-cp) rats as a model of insulin resistance from excessive eating. SHR/NDmc-cp rats displayed overt insulin resistance with high plasma glucose, insulin, and triacylglycerol concentrations relative to control Wistar-Kyoto (WKY) rats. In contrast, streptozotocin (STZ)-treated WKY rats had high glucose but low insulin concentrations. Ectopic adipocytes were found around blood vessels in the gastrocnemius in SHR/NDmc-cp rats. Areas of perivascular adipocytes and protein expression of resistin were greater in SHR/NDmc-cp rats than in control and STZ-treated WKY rats. The level of the phosphorylated (active) form of endothelial nitric oxide synthase in the gastrocnemius was lower in SHR/NDmc-cp rats than in the other groups. Insulin-resistant SHR/NDmc-cp rats showed enlarged perivascular adipocytes and greater endothelial cell dysfunction in the gastrocnemius. PMID:24759260

  4. Renal permeability alteration precedes hypertension and involves bradykinin in the spontaneously hypertensive rat.

    PubMed Central

    Plante, G E; Bissonnette, M; Sirois, M G; Regoli, D; Sirois, P

    1992-01-01

    Vascular permeability disorders have been described in experimental models, as well as in human hypertension. We recently described the fact that vascular permeability to albumin is heterogeneous in the normal rat. In the present study, we examine the contents of Evans blue dye (EB) bound to albumin in selected organs of unanesthetized Wistar Kyoto (WKY) and in spontaneously hypertensive rats (SHR) at various stages of development of hypertension. EB was injected in the caudal vein of paired 4, 8, 12, and 16-wk-old WKY and SHR. Rats were killed 10 min after EB injection and extraction of the marker was measured in selected tissues. In additional 4 and 16-wk-old animals, bradykinin B1 and B2 receptor antagonists (BKA) were also injected with EB. Renal contents of EB bound to albumin were higher in the SHR than in the WKY: 196 +/- 9, 202 +/- 10, 182 +/- 7, and 196 +/- 9, compared with 158 +/- 8, 155 +/- 7, 138 +/- 7, and 118 +/- 6 micrograms/g dry tissue, in the 4, 8, 12, and 16-wk-old rats, respectively. In the 4-wk-old SHR and WKY, blood pressure values were normal and comparable, yet the alteration in EB permeability was already present in the SHR. Both BKA failed to alter the renal EB extravasation in the WKY, but the B2-BKA restored the renal permeability to control levels in the SHR. We conclude that a selective defect in the renal vascular permeability to EB developed in the SHR. Since this finding precedes hypertension and is corrected by a selective B2-BKA, it is suggested that bradykinin is involved at an early stage of the disease in the SHR. PMID:1602008

  5. Potassium channels and vascular reactivity in genetically hypertensive rats.

    PubMed

    Furspan, P B; Webb, R C

    1990-06-01

    In hypertension, membrane potassium permeability and vascular reactivity are increased. This study characterizes a potassium-selective channel and contractions to barium, a potassium channel inhibitor, in vascular smooth muscle (tail artery) from spontaneously hypertensive stroke-prone rats (SHRSP) and normotensive Wistar-Kyoto (WKY) rats. Smooth muscle cells were isolated by enzymatic digestion, and potassium channel activity was characterized by using patch-clamp technique (inside-out configuration). Isometric contractile activity was evaluated in helically cut arterial strips by using standard muscle bath methodology. In membrane patches, a voltage-gated, calcium-insensitive, potassium-selective channel of large conductance (200 picosiemens) was observed. The channel did not conduct sodium or rubidium. Barium (10(-6) to 10(-4) M) produced a dose-dependent blockade of channel activity. These channel characteristics did not differ in SHRSP and WKY rat cells. After treatment with 35 mM KCl, barium (10(-5) to 10(-3) M) caused greater contractions in SHRSP arteries compared with arteries in WKY rats. The contractions to barium were markedly attenuated in calcium-free solution, and nifedipine and verapamil abolished contractions induced by barium in depolarizing solution. We conclude that increased vascular reactivity to barium in SHRSP arteries is not due to an alteration in the biophysical properties of the potassium channel studied. PMID:2351424

  6. A model of chronic heart failure in spontaneous hypertensive rats (SHR).

    PubMed

    Itter, G; Jung, W; Juretschke, P; Schoelkens, B A; Linz, W

    2004-04-01

    Common models of chronic heart failure (CHF) do not always result in parameters and symptoms that can be extrapolated to the clinical situation of patients with end-stage heart failure. The aim of this study was to establish and validate a new model of CHF in the rat. CHF was induced in Wistar Kyoto (WKY/NHsd) and spontaneously hypertensive (SHR/NHsd) rats by creating a permanent (8-week) occlusion of the left coronary artery 2 mm distal to the origin from the aorta by a modified technique. This resulted in a large infarction of the free left ventricular wall. The focus of attention was the validation of the geometric properties of the left ventricle and its contractility. The validation of the geometric properties of the left ventricle was done by a non-invasive magnetic resonance imaging (MRI) technique and by planimetry (stereology). Cardiodynamics (e.g. contractility) were evaluated in the isolated 'working heart' model. We were able to establish a new and predictive model of heart failure in the spontaneously hypertensive rat 8 weeks after coronary artery ligation. At this time point, the WKY rat did not show any symptoms of CHF. The model represents characteristic parameters and symptoms that can be extrapolated to the clinical situation of patients with end-stage heart failure (NYHA III-IV). Upon inspection, severe clinical symptoms of congestive heart failure were prominent, such as dyspnoea, subcutaneous oedema, pale-bluish limbs and impaired motion. Non-invasive sequential measurements by NMR techniques showed lung oedema, hydrothorax, large dilated left and right ventricular chambers and hypertrophy of the septum. The infarcted animals showed a reduced heart power, diminished contractility and enhanced heart work, much more so in the SHR/NHsd rat than in the WKY/NHsd rat. Furthermore the infarcted animals showed enhanced levels of hydroxyproline/proline ratios, again much more so in the SHR/NHsd rat than in the WKY/NHsd rat. PMID:15070453

  7. The Effects of Methylphenidate on Goal-directed Behavior in a Rat Model of ADHD

    PubMed Central

    Natsheh, Joman Y.; Shiflett, Michael W.

    2015-01-01

    Although attentional and motor alterations in Attention Deficit Hyperactivity Disorder (ADHD) have been well characterized, less is known about how this disorder impacts goal-directed behavior. To investigate whether there is a misbalance between goal-directed and habitual behaviors in an animal model of ADHD, we tested adult [P75–P105] Spontaneously Hypertensive Rats (SHR; ADHD rat model) and Wistar–Kyoto rats (WKY), the normotensive control strain, on an instrumental conditioning paradigm with two phases: a free-operant training phase in which rats separately acquired two distinct action–outcome contingencies, and a choice test conducted in extinction prior to which one of the food outcomes was devalued through specific satiety. To assess the effects of Methylphenidate (MPH), a commonly used ADHD medication, on goal-directed behavior, we injected rats with either MPH or saline prior to the choice test. Both rat strains acquired an instrumental response, with SHR responding at greater rates over the course of training. During the choice test WKY demonstrated goal-directed behavior, responding more frequently on the lever that delivered, during training, the still-valued outcome. In contrast, SHR showed no goal-directed behavior, responding equally on both levers. However, MPH administration prior to the choice test restored goal-directed behavior in SHR, and disrupted this behavior in WKY rats. This study provides the first experimental evidence for selective impairment in goal-directed behavior in rat models of ADHD, and how MPH acts differently on SHR and WKY animals to restore or impair this behavior, respectively. PMID:26635568

  8. Prostatic Relaxation Induced by Loperamide Is Reduced in Spontaneously Hypertensive Rats

    PubMed Central

    Lee, Liang-Ming; Lu, Chih-Cheng; Chung, Hsien-Hui; Cheng, Juei-Tang

    2012-01-01

    This paper shows a new finding about the decrease of relaxative response to loperamide in prostate of spontaneously hypertensive rats (SHR) as compare to normal rats (WKY). Authors demonstrated the reduction of ATP-sensitive potassium channels is resposible for this change using immunoblotting analysis and the decrease of action induced by diazoxide. This view is not mentioned before and is the first one reporting this result. PMID:22645476

  9. The Effects of Methylphenidate on Goal-directed Behavior in a Rat Model of ADHD.

    PubMed

    Natsheh, Joman Y; Shiflett, Michael W

    2015-01-01

    Although attentional and motor alterations in Attention Deficit Hyperactivity Disorder (ADHD) have been well characterized, less is known about how this disorder impacts goal-directed behavior. To investigate whether there is a misbalance between goal-directed and habitual behaviors in an animal model of ADHD, we tested adult [P75-P105] Spontaneously Hypertensive Rats (SHR; ADHD rat model) and Wistar-Kyoto rats (WKY), the normotensive control strain, on an instrumental conditioning paradigm with two phases: a free-operant training phase in which rats separately acquired two distinct action-outcome contingencies, and a choice test conducted in extinction prior to which one of the food outcomes was devalued through specific satiety. To assess the effects of Methylphenidate (MPH), a commonly used ADHD medication, on goal-directed behavior, we injected rats with either MPH or saline prior to the choice test. Both rat strains acquired an instrumental response, with SHR responding at greater rates over the course of training. During the choice test WKY demonstrated goal-directed behavior, responding more frequently on the lever that delivered, during training, the still-valued outcome. In contrast, SHR showed no goal-directed behavior, responding equally on both levers. However, MPH administration prior to the choice test restored goal-directed behavior in SHR, and disrupted this behavior in WKY rats. This study provides the first experimental evidence for selective impairment in goal-directed behavior in rat models of ADHD, and how MPH acts differently on SHR and WKY animals to restore or impair this behavior, respectively. PMID:26635568

  10. The Left Hand Second to Fourth Digit Ratio (2D:4D) Does Not Discriminate World-Class Female Gymnasts from Age Matched Sedentary Girls

    PubMed Central

    Peeters, Maarten W.; Claessens, Albrecht L.

    2012-01-01

    Introduction The second to fourth-digit-ratio (2D:4D), a putative marker of prenatal androgen action and a sexually dimorphic trait, has been suggested to be related with sports performance, although results are not univocal. If this relation exists, it is most likely to be detected by comparing extreme groups on the continuum of sports performance. Methods In this study the 2D:4D ratio of world-class elite female artistic gymnasts (n = 129), competing at the 1987 Rotterdam World-Championships was compared to the 2D:4D ratio of sedentary age-matched sedentary girls (n = 129), alongside with other anthropometric characteristics including other sexually dimorphic traits such as an androgyny index (Bayer & Bayley) and Heath-Carter somatotype components (endomorphy, mesomorphy, ectomorphy) using AN(C)OVA. 2D:4D was measured on X-rays of the left hand. Results Left hand 2D:4D digit ratio in world class elite female gymnasts (0.921±0.020) did not differ significantly from 2D:4D in age-matched sedentary girls (0.924±0.018), either with or without inclusion of potentially confounding covariates such as skeletal age, height, weight, somatotype components or androgyny index. Height (161.9±6.4 cm vs 155.4±6.6 cm p<0.01), weight (53.9±7.6 kg vs 46.2 6.3 kg p<0.01), BMI (20.51±2.41 kg/m2 vs 19.05±1.56 kg/m2), skeletal age (15.2±1.1 y vs 14.5±1.2 y p>0.01), somatotype components (4.0/3.0/2.9 vs 1.7/3.7/3.2 for endomorphy (p<0.01), mesomorphy (p<0.01) and ectomorphy (p<0.05) respectively) all differed significantly between sedentary girls and elite gymnasts. As expressed by the androgyny index, gymnasts have, on average, broader shoulders relative to their hips, compared to the reference sample. Correlations between the 2D:4D ratio and chronological age, skeletal age, and the anthropometric characteristics are low and not significant. Conclusion Although other anthropometric characteristics of sexual dimorphism were significantly different between the two samples

  11. Increased Nonconducted P-Wave Arrhythmias after a Single Oil Fly Ash Inhalation Exposure in Hypertensive Rats

    PubMed Central

    Farraj, Aimen K.; Haykal-Coates, Najwa; Winsett, Darrell W.; Hazari, Mehdi S.; Carll, Alex P.; Rowan, William H.; Ledbetter, Allen D.; Cascio, Wayne E.; Costa, Daniel L.

    2009-01-01

    Background Exposure to combustion-derived fine particulate matter (PM) is associated with increased cardiovascular morbidity and mortality especially in individuals with cardiovascular disease, including hypertension. PM inhalation causes several adverse changes in cardiac function that are reflected in the electrocardiogram (ECG), including altered cardiac rhythm, myocardial ischemia, and reduced heart rate variability (HRV). The sensitivity and reliability of ECG-derived parameters as indicators of the cardiovascular toxicity of PM in rats are unclear. Objective We hypothesized that spontaneously hypertensive (SH) rats are more susceptible to the development of PM-induced arrhythmia, altered ECG morphology, and reduced HRV than are Wistar Kyoto (WKY) rats, a related strain with normal blood pressure. Methods We exposed rats once by nose-only inhalation for 4 hr to residual oil fly ash (ROFA), an emission source particle rich in transition metals, or to air and then sacrificed them 1 or 48 hr later. Results ROFA-exposed SH rats developed nonconducted P-wave arrhythmias but no changes in ECG morphology or HRV. We found no ECG effects in ROFA-exposed WKY rats. ROFA-exposed SH rats also had greater pulmonary injury, neutrophil infiltration, and serum C-reactive protein than did ROFA-exposed WKY rats. Conclusions These results suggest that cardiac arrhythmias may be an early sensitive indicator of the propensity for PM inhalation to modify cardiovascular function. PMID:19479011

  12. Neuromedin U causes biphasic cardiovascular effects and impairs baroreflex function in rostral ventrolateral medulla of spontaneously hypertensive rat.

    PubMed

    Rahman, Ahmed A; Shahid, Israt Z; Pilowsky, Paul M

    2013-06-01

    Neuromedin U (NMU) causes biphasic cardiovascular and sympathetic responses and attenuates adaptive reflexes in the rostral ventrolateral medulla (RVLM) and spinal cord in normotensive animal. However, the role of NMU in the pathogenesis of hypertension is unknown. The effect of NMU on baseline cardiorespiratory variables in the RVLM and spinal cord were investigated in urethane-anaesthetized, vagotomized and artificially ventilated male spontaneously hypertensive rats (SHR) and Wistar-Kyoto rats (WKY). Experiments were also conducted to determine the effects of NMU on somatosympathetic and baroreceptor reflexes in the RVLM of SHR and WKY. NMU injected into the RVLM and spinal cord elicited biphasic response, a brief pressor and sympathoexcitatory response followed by a prolonged depressor and sympathoinhibitory response in both hypertensive and normotensive rat models. The pressor, sympathoexcitatory and sympathoinhibitory responses evoked by NMU were exaggerated in SHR. Phrenic nerve amplitude was also increased following intrathecal or microinjection of NMU into the RVLM of both strains. NMU injection into the RVLM attenuated the somatosympathetic reflex in both SHR and WKY. Baroreflex sensitivity was impaired in SHR at baseline and further impaired following NMU injection into the RVLM. NMU did not affect baroreflex activity in WKY. The present study provides functional evidence that NMU can have an important effect on the cardiovascular and reflex responses that are integrated in the RVLM and spinal cord. A role for NMU in the development and maintenance of essential hypertension remains to be determined. PMID:23538213

  13. Effect of Selenium Supplementation on Redox Status of the Aortic Wall in Young Spontaneously Hypertensive Rats

    PubMed Central

    Ruseva, Boryana; Atanasova, Milena; Tsvetkova, Reni; Betova, Tatyana; Mollova, Margarita; Alexandrova, Margarita; Laleva, Pavlina; Dimitrova, Aneliya

    2015-01-01

    Selenium (Se) is an exogenous antioxidant that performs its function via the expression of selenoproteins. The aim of this study was to explore the effect of varying Se intake on the redox status of the aortic wall in young spontaneously hypertensive rats (SHR). Sixteen male Wistar Kyoto (WKY) rats and nineteen male SHR, 16-week-old, were tested after being given diets with different Se content for eight weeks. They were divided into 4 groups: control groups of WKY NSe and SHR NSe on an adequate Se diet and groups of WKY HSe and SHR HSe that received Se supplementation. The Se nutritional status was assessed by measuring whole blood glutathione peroxidase-1 (GPx-1) activity. Serum concentration of lipid hydroperoxides and serum level of antibodies against advanced glycation end products (anti-AGEs abs) were determined. Expression of GPx-1 and endothelial nitric oxide synthase (eNOS) were examined in aortic wall. Se supplementation significantly increased GPx-1 activity of whole blood and in the aortas of WKY and SHR. Decreased lipid peroxidation level, eNOS-3 expression in the aortic wall, and serum level of anti-AGEs abs were found in SHR HSe compared with SHR NSe. In conclusion, Se supplementation improved the redox status of the aortic wall in young SHR. PMID:26473024

  14. Immunity in young adult survivors of childhood leukemia is similar to the elderly rather than age-matched controls: Role of cytomegalovirus.

    PubMed

    Azanan, Mohamad Shafiq; Abdullah, Noor Kamila; Chua, Ling Ling; Lum, Su Han; Abdul Ghafar, Sayyidatul Syahirah; Kamarulzaman, Adeeba; Kamaruzzaman, Shahrul; Lewin, Sharon R; Woo, Yin Ling; Ariffin, Hany; Rajasuriar, Reena

    2016-07-01

    Many treatment complications that occur late in childhood cancer survivors resemble age-related comorbidities observed in the elderly. An immune phenotype characterized by increased immune activation, systemic inflammation, and accumulation of late-differentiated memory CD57(+) CD28(-) T cells has been associated with comorbidities in the elderly. Here, we explored if this phenotype was present in young adult leukemia survivors following an average of 19 years from chemotherapy and/or radiotherapy completion, and compared this with that in age-matched controls. We found that markers of systemic inflammation-IL-6 and human C-reactive protein and immune activation-CD38 and HLA-DR on T cells, soluble CD (sCD)163 from monocytes and macrophages-were increased in survivors compared to controls. T-cell responses specific to cytomegalovirus (CMV) were also increased in survivors compared to controls while CMV IgG levels in survivors were comparable to levels measured in the elderly (>50years) and correlated with IL-6, human C-reactive protein, sCD163, and CD57(+) CD28(-) memory T cells. Immune activation and inflammation markers correlated poorly with prior chemotherapy and radiotherapy exposure. These data suggest that CMV infection/reactivation is strongly correlated with the immunological phenotype seen in young childhood leukemia survivors and these changes may be associated with the early onset of age-related comorbidities in this group. PMID:27129782

  15. ANTIDEPRESSANT-LIKE EFFECTS OF LOW KETAMINE DOSE IS ASSOCIATED WITH INCREASED HIPPOCAMPAL AMPA/NMDA RECEPTOR DENSITY RATIO IN FEMALE WISTAR-KYOTO RATS

    PubMed Central

    Tizabi, Yousef; Bhatti, Babur H; Manaye, Kebreten F; Das, Jharna R; Akinfiresoye, Luli

    2012-01-01

    Preclinical as well as limited clinical studies indicate that ketamine, a non-competitive glutamate NMDA receptor antagonist, may exert a quick and prolonged antidepressant effect. It has been postulated that ketamine action is due to inhibition of NMDA and stimulation of AMPA receptors. Here, we sought to determine whether ketamine would exert antidepressant effects in Wistar-Kyoto (WKY) rats, a putative animal model of depression and whether this effect would be associated with changes in AMPA/NMDA receptor densities in the hippocampus. Adult female WKY rats and their control Wistar rats were subjected to acute and chronic ketamine doses and their locomotor activity (LMA) and immobility in the forced swim test (FST) were evaluated. Hippocampal AMPA and NMDA receptor densities were also measured following a chronic ketamine dose. Ketamine, both acutely (0.5–5.0 mg/kg ip) and chronically (0.5–2.5 mg/kg daily for 10 days) resulted in a dose-dependent and prolonged decrease in immobility in the FST in WKY rats only, suggesting an antidepressant-like effect in this model. Chronic treatment with an effective dose of ketamine also resulted in an increase in AMPA/NMDA receptor density ratio in the hippocampus of WKY rats. LMA was not affected by any ketamine treatment in either strain. These results indicate a rapid and lasting antidepressant-like effect of a low ketamine dose in WKY rat model of depression. Moreover, the increase in AMPA/NMDA receptor density in hippocampus could be a contributory factor to behavioral effects of ketamine. These findings suggest potential therapeutic benefit in simultaneous reduction of central NMDA and elevation of AMPA receptor function in treatment of depression. PMID:22521815

  16. Spontaneously hypertensive rats (SHR) as a putative animal model of childhood hyperkinesis: SHR behavior compared to four other rat strains.

    PubMed

    Sagvolden, T; Pettersen, M B; Larsen, M C

    1993-12-01

    Childhood hyperkinesis or attention-deficit hyperactivity disorder (ADHD) is a behavior disorder of which the main symptoms are attention problems and hyperactivity. The main objective of the present study was to investigate whether the spontaneously hypertensive rat (SHR) strain is a useful animal model of ADHD. Five different rat strains were tested: SHR, Wistar-Kyoto (WKY), Wistar, Sprague-Dawley (SPRD), and PVG (hooded) rats. The protocol consisted of three different test procedures: 1) A 7.5-min free-exploration open-field test (home cage accessible), where the SHR was less active than Wistar and SPRD but more active than WKY; SHR showed longer latencies to leave the home cage than both Wistar and SPRD rats, spending less time in the field, ambulating and rearing less than Wistar and SPRD but more than WKY. Within session, the SHR tended to be more active at the end of the session than at the start, while the opposite tended to be the case in the other groups. 2) A 7.5-min forced exploration open-field test (home cage not accessible), where the results showed that the SHR is less active than both the Wistar and Sprague-Dawley strains, but more active than PVG and WKY. 3) A two-component multiple schedule of reinforcement with a fixed interval 2 min signalled by houselight on and a 5-min extinction signalled by houselight off. Lever pressing by SHR was markedly different from that of the other four strains, which were quite Except early in the interval, SHR pressed the lever more than any of the other groups.(ABSTRACT TRUNCATED AT 250 WORDS) PMID:8295939

  17. Longitudinal Evaluation of Sympathetic Nervous System and Perfusion in Normal and Spontaneously Hypertensive Rat Hearts with Dynamic Single-Photon Emission Computed Tomography.

    PubMed

    Zan, Yunlong; Boutchko, Rostyslav; Huang, Qiu; Li, Biao; Chen, Kewei; Gullberg, Grant T

    2015-01-01

    The objective of this work was to evaluate the sympathetic nervous system and structure remodeling during the progression of heart failure in a rodent model using dynamic cardiac single-photon emission computed tomography (SPECT). The spontaneously hypertensive rat (SHR) model was used to study changes in the nervous system innervation and perfusion in the left ventricular (LV) myocardium with the progression of left ventricular hypertrophy (LVH) to heart failure. Longitudinal dynamic SPECT studies were performed with seven SHR and seven Wistar-Kyoto (WKY) rats over 1.5 years using a dual-head SPECT scanner with pinhole collimators. Time-activity curves (TACs) of the 123I-MIBG and 201Tl distribution in the LV blood pool and myocardium were extracted from dynamic SPECT data and fitted to compartment models to determine the influx rate, washout rate, and distribution volume (DV) of 123I-MIBG and 201Tl in the LV myocardium. The standardized uptake values (SUVs) of 123I-MIBG and 201Tl in the LV myocardium were also calculated from the static reconstructed images. The influx and washout rates of 123I-MIBG did not show a significant difference between SHRs and WKY rats. The DVs of 123I-MIBG were greater in the SHRs than in the WKY rats (p = .0028). Specifically, the DV of 123I-MIBG became greater in the SHRs by 6 months of age (p = .0017) and was still significant at the age of 22 months. The SUV of 123I-MIBG in SHRs exhibited abnormal values compared to WKY rats from the age of 18 months. There was no difference in the influx rate and the washout rate of 201Tl between the SHRs and WKY rats. The SHRs exhibited greater DV of 201Tl than WKY rats after the age of 18 months (p = .034). The SUV of 201Tl in SHRs did not show any significant difference from WKY at all ages. The higher DV of 123I-MIBG in the LV myocardium reveals abnormal nervous system activity of the SHRs at an age of 6 months, whereas a greater DV of 201Tl in the LV myocardium can only be detected at an age

  18. Role of Musclin in the Pathogenesis of Hypertension in Rat

    PubMed Central

    Li, Ying-Xiao; Cheng, Kai-Chun; Asakawa, Akihiro; Kato, Ikuo; Sato, Yuki; Amitani, Haruka; Kawamura, Namiko; Cheng, Juei-Tang; Inui, Akio

    2013-01-01

    Musclin is a novel skeletal muscle-derived secretory factor found in the signal sequence trap of mouse skeletal muscle cDNAs. Musclin possesses a region homologous to the natriuretic peptide family. Thus, musclin is found to bind with the natriuretic peptide clearance receptors. However, the role of musclin in vascular regulation remains unclear. In this study, we aim to investigate the direct effect of musclin on vascular tone and to analyze its role in hypertension using the spontaneously hypertensive rats (SHR). In aortic strips isolated from SHR, musclin induced contractions in a dose-dependent manner. We found that the musclin-induced vasoconstriction was more marked in SHR than in normal rats (WKY). Moreover, this contraction was reduced by blockade of natriuretic peptide receptor C using the ab14355 antibody. Therefore, mediation of the natriuretic peptide receptor in musclin-induced vasoconstriction can be considered. In addition, similar to the natriuretic peptide receptor, expression of the musclin gene in blood vessels was higher in SHR than in WKY. Injection of musclin markedly increased the blood pressure in rats that can be inhibited by anti-musclin antibodies. Musclin-induced vasoconstriction was more pronounced in SHR than in WKY as in its expression. Taken together, these results suggest that musclin is involved in blood pressure regulation. The higher expression of musclin in hypertension indicates that musclin could be used as a new target for the treatment of hypertension in the future. PMID:23940802

  19. Subchronic toxicity and cardiovascular responses in spontaneously hypertensive rats after exposure to multiwalled carbon nanotubes by intratracheal instillation.

    PubMed

    Chen, Rui; Zhang, Lili; Ge, Cuicui; Tseng, Michael T; Bai, Ru; Qu, Ying; Beer, Christiane; Autrup, Herman; Chen, Chunying

    2015-03-16

    The tremendous demand of the market for carbon nanotubes has led to their massive production that presents an increasing risk through occupational exposure. Lung deposition of carbon nanotubes is known to cause acute localized pulmonary adverse effects. However, systemic cardiovascular damages associated with acute pulmonary lesion have not been thoroughly addressed. Four kinds of multiwalled carbon nanotubes (MWCNTs) with different lengths and/or iron contents were used to explore the potential subchronic toxicological effects in spontaneously hypertensive (SH) rats and normotensive control Wistar-Kyoto (WKY) rats after intratracheal instillation. MWCNTs penetrated the lung blood-gas barrier and accumulated in the liver, kidneys, and spleen but not in the heart and aorta of SH rats. The pulmonary toxicity and cardiovascular effects were assessed at 7 and 30 days postexposure. Compared to the WKY rats, transient influences on blood pressure and up to 30 days persistent decrease in the heart rate of SH rats were found by electrocardiogram monitoring. The subchronic toxicity, especially the sustained inflammation of the pulmonary and cardiovascular system, was revealed at days 7 and 30 in both SH and WKY rat models. Histopathological results showed obvious morphological lesions in abdominal arteries of SH rats 30 days after exposure. Our results suggest that more attention should be paid to the long-term toxic effects of MWCNTs, and particularly, occupationally exposed workers with preexisting cardiovascular diseases should be monitored more thoroughly. PMID:25580880

  20. Pasta containing tartary buckwheat sprouts prevents DNA damage in spontaneously hypertensive rats.

    PubMed

    Meschini, Roberta; Filippi, Silvia; Molinari, Romina; Costantini, Lara; Bonafaccia, Giovanni; Merendino, Nicolò

    2015-01-01

    Recent studies have shown that DNA damage occurs more often in hypertensive patients than non-hypertensive individuals. Here, we analyzed the in vivo effect of pasta containing 30% of tartary buckwheat sprouts (TBSP) on spontaneously hypertensive rats (SHRs) and normotensive Wistar Kyoto rats (WKY) to elucidate if TBSP could have an anti-genotoxic effect in hypertensive animal models. Both SHRs and WKY rats were divided into two groups and fed for six weeks with 5 g of TBSP and durum wheat flour commercial pasta, respectively. Our results showed that a diet rich in TBSP has anti-genotoxic effect. Indeed, SHRs fed with TBSP exhibited a significant decrease in DNA damage (38%) and more efficient DNA repair (84%) compared to SHRs fed with commercial pasta. PMID:26068704

  1. Stable Schizophrenia Patients Learn Equally Well as Age-Matched Controls and Better than Elderly Controls in Two Sensorimotor Rotary Pursuit Tasks

    PubMed Central

    De Picker, Livia J.; Cornelis, Claudia; Hulstijn, Wouter; Dumont, Glenn; Fransen, Erik; Timmers, Maarten; Janssens, Luc; Morrens, Manuel; Sabbe, Bernard G. C.

    2014-01-01

    Objective: To compare sensorimotor performance and learning in stable schizophrenia patients, healthy age- and sex-matched controls and elderly controls on two variations of the rotary pursuit: circle pursuit (true motor learning) and figure pursuit (motor and sequence learning). Method: In the circle pursuit, a target circle, rotating with increasing speed along a predictable circular path on the computer screen, must be followed by a cursor controlled by a pen on a writing tablet. In the eight-trial figure pursuit, subjects learn to draw a complex figure by pursuing the target circle that moves along an invisible trajectory between and around several goals. Tasks were administered thrice (day 1, day 2, day 7) to 30 patients with stable schizophrenia (S), 30 healthy age- and sex-matched controls (C), and 30 elderly participants (>65 years; E) and recorded with a digitizing tablet and pressure-sensitive pen. The outcome measure accuracy (% of time that cursor is within the target) was used to assess performance. Results: We observed significant group differences in accuracy, both in circle and figure pursuit tasks (E < S < C, p < 0.01). Strong learning effects were found in each group. Learning curves were similar in circle pursuit but differed between groups in figure pursuit. When corrected for group differences in starting level, the learning gains over the three sessions of schizophrenia patients and age-matched controls were equal and both were larger than those of the elderly controls. Conclusion: Despite the reduced sensorimotor performance that was found in the schizophrenia patients, their sensorimotor learning seems to be preserved. The relevance of this finding for the evaluation of procedural learning in schizophrenia is discussed. The better performance and learning rate of the patients compared to the elderly controls was unexpected and deserves further study. PMID:25505425

  2. RELN-expressing Neuron Density in Layer I of the Superior Temporal Lobe is Similar in Human Brains with Autism and in Age-Matched Controls

    PubMed Central

    Camacho, Jasmin; Ejaz, Ehsan; Ariza, Jeanelle; Noctor, Stephen C.; Martínez-Cerdeño, Verónica

    2015-01-01

    Reelin protein (RELN) level is reduced in the cerebral cortex and cerebellum of subjects with autism. RELN is synthesized and secreted by a subpopulation of neurons in the developing cerebral cortex termed Cajal-Retzius (CR) cells. These cells are abundant in the marginal zone during cortical development, many die after development is complete, but a small population persists into adulthood. In adult brains, RELN is secreted by the surviving CR cells, by a subset of GABAergic interneurons in layer I, and by pyramidal cells and GABAergic interneurons in deeper cortical layers. It is widely believed that decreased RELN in layer I of the cerebral cortex of subjects with autism may result from a decrease in the density of RELN expressing neurons in layer I; however, this hypothesis has not been tested. We examined RELN expression in layer I of the adult human cortex and found that 70% of cells express RELN in both control and autistic subjects. We quantified the density of neurons in layer I of the superior temporal cortex of subjects with autism and age-matched control subjects. Our data show that there is no change in the density of neurons in layer I of the cortex of subjects with autism, and therefore suggest that reduced RELN expression in the cerebral cortex of subjects with autism is not a consequence of decreased numbers of RELN-expressing neurons in layer I. Instead reduced RELN may result from abnormal RELN processing, or a decrease in the number of other RELN-expressing neuronal cell types. PMID:25067827

  3. No consistent difference in gray matter volume between individuals with fibromyalgia and age-matched healthy subjects when controlling for affective disorder.

    PubMed

    Hsu, Michael C; Harris, Richard E; Sundgren, Pia C; Welsh, Robert C; Fernandes, Carlo R; Clauw, Daniel J; Williams, David A

    2009-06-01

    Fibromyalgia (FM) is thought to involve abnormalities in central pain processing. Recent studies involving small samples have suggested alterations in gray matter volume (GMV) in brains of FM patients. Our objective was to verify these findings in a somewhat larger sample using voxel-based morphometry (VBM), while controlling for the presence of affective disorders (AD). T1-weighted magnetic resonance image (MRI) brain scans were obtained on 29 FM patients with AD, 29 FM patients without AD, and 29 age-matched healthy controls (HCs) using a 3T scanner. Segmentation, spatial normalization, and volumetric modulation were performed using an automated protocol within SPM5. Smoothed gray matter segments were entered into a voxel-wise one-way ANOVA, and a search for significant clusters was performed using thresholding methods published in previous studies (whole-brain threshold of p<.05 correcting for multiple comparisons; region-of-interest (ROI) threshold of p< or =.001 uncorrected, or p<.05 small-volume corrected). The whole-brain analysis did not reveal any significant clusters. ROI-based analysis revealed a significant difference in left anterior insula GMV among the three groups (xyz={-28, 21, 9}; p=.026, corrected). However, on post-hoc testing, FM patients without AD did not differ significantly from HC with respect to mean GMV extracted from this cluster. A significant negative correlation was found between mean cluster GMV and scores of trait anxiety (State-Trait Personality Inventory, Trait Anxiety scale; rho=-.470, p<.001). No other significant clusters were found on ROI-based analysis. Our results emphasize the importance of correcting for AD when carrying out VBM studies in chronic pain. PMID:19375224

  4. No Consistent Difference in Gray Matter Volume between Individuals with Fibromyalgia and Age-Matched Healthy Subjects when Controlling for Affective Disorder

    PubMed Central

    Hsu, Michael C.; Harris, Richard E.; Sundgren, Pia C.; Welsh, Robert C.; Fernandes, Carlo R.; Clauw, Daniel J.; Williams, David A.

    2009-01-01

    Fibromyalgia (FM) is thought to involve abnormalities in central pain processing. Recent studies involving small samples have suggested alterations in gray matter volume (GMV) in brains of FM patients. Our objective was to verify these findings in a somewhat larger sample using voxel-based morphometry (VBM), while controlling for presence of affective disorders (AD). T1-weighted magnetic resonance image (MRI) brain scans were obtained on 29 FM patients with AD, 29 FM patients without AD, and 29 age-matched healthy controls (HC) using a 3T scanner. Segmentation, spatial normalization, and volumetric modulation were performed using an automated protocol within SPM5. Smoothed gray matter segments were entered into a voxel-wise one-way ANOVA, and a search for significant clusters was performed using thresholding methods published in previous studies (whole-brain threshold of p<.05 correcting for multiple comparisons; region-of-interest (ROI) threshold of p≤.001 uncorrected, or p<.05 small-volume corrected). The whole-brain analysis did not reveal any significant clusters. ROI-based analysis revealed a significant difference in left anterior insula GMV among the three groups (xyz={−28, 21, 9}; p=.026, corrected). However, on post-hoc testing, FM patients without AD did not differ significantly from HC with respect to mean GMV extracted from this cluster. A significant negative correlation was found between mean cluster GMV and scores of trait anxiety (State-Trait Personality Inventory, Trait Anxiety scale; rho=−.470, p<.001). No other significant clusters were found on ROI-based analysis. Our results emphasize the importance of correcting for AD when carrying out VBM studies in chronic pain. PMID:19375224

  5. New Wistar Kyoto and spontaneously hypertensive rat transgenic models with ubiquitous expression of green fluorescent protein

    PubMed Central

    Garcia Diaz, Ana Isabel; Moyon, Ben; Coan, Philip M.; Alfazema, Neza; Venda, Lara; Woollard, Kevin; Aitman, Tim

    2016-01-01

    ABSTRACT The Wistar Kyoto (WKY) rat and the spontaneously hypertensive (SHR) rat inbred strains are well-established models for human crescentic glomerulonephritis (CRGN) and metabolic syndrome, respectively. Novel transgenic (Tg) strains add research opportunities and increase scientific value to well-established rat models. We have created two novel Tg strains using Sleeping Beauty transposon germline transgenesis, ubiquitously expressing green fluorescent protein (GFP) under the rat elongation factor 1 alpha (EF1a) promoter on the WKY and SHR genetic backgrounds. The Sleeping Beauty system functioned with high transgenesis efficiency; 75% of new rats born after embryo microinjections were transgene positive. By ligation-mediated PCR, we located the genome integration sites, confirming no exonic disruption and defining a single or low copy number of the transgenes in the new WKY-GFP and SHR-GFP Tg lines. We report GFP-bright expression in embryos, tissues and organs in both lines and show preliminary in vitro and in vivo imaging data that demonstrate the utility of the new GFP-expressing lines for adoptive transfer, transplantation and fate mapping studies of CRGN, metabolic syndrome and other traits for which these strains have been extensively studied over the past four decades. PMID:26769799

  6. New Wistar Kyoto and spontaneously hypertensive rat transgenic models with ubiquitous expression of green fluorescent protein.

    PubMed

    Garcia Diaz, Ana Isabel; Moyon, Ben; Coan, Philip M; Alfazema, Neza; Venda, Lara; Woollard, Kevin; Aitman, Tim

    2016-04-01

    The Wistar Kyoto (WKY) rat and the spontaneously hypertensive (SHR) rat inbred strains are well-established models for human crescentic glomerulonephritis (CRGN) and metabolic syndrome, respectively. Novel transgenic (Tg) strains add research opportunities and increase scientific value to well-established rat models. We have created two novel Tg strains using Sleeping Beauty transposon germline transgenesis, ubiquitously expressing green fluorescent protein (GFP) under the rat elongation factor 1 alpha (EF1a) promoter on the WKY and SHR genetic backgrounds. The Sleeping Beauty system functioned with high transgenesis efficiency; 75% of new rats born after embryo microinjections were transgene positive. By ligation-mediated PCR, we located the genome integration sites, confirming no exonic disruption and defining a single or low copy number of the transgenes in the new WKY-GFP and SHR-GFP Tg lines. We report GFP-bright expression in embryos, tissues and organs in both lines and show preliminaryin vitroandin vivoimaging data that demonstrate the utility of the new GFP-expressing lines for adoptive transfer, transplantation and fate mapping studies of CRGN, metabolic syndrome and other traits for which these strains have been extensively studied over the past four decades. PMID:26769799

  7. Differential Responses to Blood Pressure and Oxidative Stress in Streptozotocin-Induced Diabetic Wistar-Kyoto Rats and Spontaneously Hypertensive Rats: Effects of Antioxidant (Honey) Treatment

    PubMed Central

    Erejuwa, Omotayo O.; Sulaiman, Siti A.; Wahab, Mohd Suhaimi Ab; Sirajudeen, Kuttulebbai N. S.; Salleh, Md Salzihan Md; Gurtu, Sunil

    2011-01-01

    Oxidative stress is implicated in the pathogenesis and/or complications of hypertension and/or diabetes mellitus. A combination of these disorders increases the risk of developing cardiovascular events. This study investigated the effects of streptozotocin (60 mg/kg; ip)-induced diabetes on blood pressure, oxidative stress and effects of honey on these parameters in the kidneys of streptozotocin-induced diabetic Wistar-Kyoto (WKY) and spontaneously hypertensive rats (SHR). Diabetic WKY and SHR were randomized into four groups and received distilled water (0.5 mL) and honey (1.0 g/kg) orally once daily for three weeks. Control SHR had reduced malondialdehyde (MDA) and increased systolic blood pressure (SBP), catalase (CAT) activity, and total antioxidant status (TAS). SBP, activities of glutathione peroxidase (GPx) and glutathione reductase (GR) were elevated while TAS was reduced in diabetic WKY. In contrast, SBP, TAS, activities of GPx and GR were reduced in diabetic SHR. Antioxidant (honey) treatment further reduced SBP in diabetic SHR but not in diabetic WKY. It also increased TAS, GSH, reduced glutathione (GSH)/oxidized glutathione (GSSG) ratio, activities of GPx and GR in diabetic SHR. These data suggest that differences in types, severity, and complications of diseases as well as strains may influence responses to blood pressure and oxidative stress. PMID:21673929

  8. Repeated forced swim stress differentially affects formalin-evoked nociceptive behaviour and the endocannabinoid system in stress normo-responsive and stress hyper-responsive rat strains.

    PubMed

    Jennings, Elaine M; Okine, Bright N; Olango, Weredeselam M; Roche, Michelle; Finn, David P

    2016-01-01

    Repeated exposure to a homotypic stressor such as forced swimming enhances nociceptive responding in rats. However, the influence of genetic background on this stress-induced hyperalgesia is poorly understood. The aim of the present study was to compare the effects of repeated forced swim stress on nociceptive responding in Sprague-Dawley (SD) rats versus the Wistar Kyoto (WKY) rat strain, a genetic background that is susceptible to stress, negative affect and hyperalgesia. Given the well-documented role of the endocannabinoid system in stress and pain, we investigated associated alterations in endocannabinoid signalling in the dorsal horn of the spinal cord and amygdala. In SD rats, repeated forced swim stress for 10 days was associated with enhanced late phase formalin-evoked nociceptive behaviour, compared with naive, non-stressed SD controls. In contrast, WKY rats exposed to 10 days of swim stress displayed reduced late phase formalin-evoked nociceptive behaviour. Swim stress increased levels of monoacylglycerol lipase (MAGL) mRNA in the ipsilateral side of the dorsal spinal cord of SD rats, an effect not observed in WKY rats. In the amygdala, swim stress reduced anandamide (AEA) levels in the contralateral amygdala of SD rats, but not WKY rats. Additional within-strain differences in levels of CB1 receptor and fatty acid amide hydrolase (FAAH) mRNA and levels of 2-arachidonylglycerol (2-AG) were observed between the ipsilateral and contralateral sides of the dorsal horn and/or amygdala. These data indicate that the effects of repeated stress on inflammatory pain-related behaviour are different in two rat strains that differ with respect to stress responsivity and affective state and implicate the endocannabinoid system in the spinal cord and amygdala in these differences. PMID:25988529

  9. Effect of treatment with vitamin D3 on the responses of the duodenum of spontaneously hypertensive rats to bradykinin and to potassium.

    PubMed Central

    Feres, T.; Vianna, L. M.; Paiva, A. C.; Paiva, T. B.

    1992-01-01

    1. The diet of spontaneously hypertensive rats (SHR) and normotensive Wistar-Kyoto (WKY) and Wistar (NWR) rats was supplemented with either 2% calcium lactate in the drinking water or 12.5 micrograms vitamin D3 100 g-1 body weight daily by gavage, for 14 days. 2. The blood pressure of the SHR treated with either calcium or vitamin D decreased to the same levels as that of WKY and NWR. 3. The response to bradykinin of the SHR isolated duodenum, which is predominantly contractile, upon treatment with vitamin D (but not with calcium), became predominantly relaxant, approaching the normal behavior of the WKY and NWR duodenum. 4. The relaxant responses of the SHR and WKY duodenum to potassium were smaller than those of NWR, but treatment with vitamin D increased the response in all three rat strains. 5. It is concluded that, besides sharing the hypotensive effect of calcium, vitamin D treatment of SHR has an effect on the duodenum smooth muscle which might be due to calmodulin-dependent activation of calcium-dependent potassium channels. PMID:1324053

  10. High resolution 23Na-nuclear magnetic resonance study of stroke-prone spontaneously hypertensive rat erythrocytes.

    PubMed

    Kwan, C Y; Seo, Y; Ito, H; Murakami, M; Watari, H

    1987-06-01

    The intracellular Na+ content of washed erythrocytes from stroke-prone spontaneously hypertensive rats (SHRSP) and Wistar-Kyoto normotensive rats (WKY) was measured by a high resolution 23Na-nuclear magnetic resonance (NMR) technique using a non-permeant aqueous shift reagent, dysprosium triethylenetetramine hexaacetic acid, Dy(TTHA)3-. The initial intracellular Na+ of freshly isolated and washed erythrocytes was very low (approximately 5 mmol/l) and increased progressively with prolonged incubation in isotonic salt solution at 37 degrees C. There was no significant difference in the erythrocyte Na+ concentration between SHRSP and WKY over the entire period of measurement, nor was any difference detected in their osmotic fragility or total cellular volume, although the osmotic fragility decreased with incubation time. The high energy phosphate metabolites were also studied in the same erythrocytes by 31P-NMR. The level of intracellular ATP decreased with incubation at 37 degrees C but showed no difference between the SHRSP and WKY samples. Inclusion of 1 mmol/l ouabain in the incubation medium substantially retarded the breakdown of intracellular ATP and resulted in a concomitant increase in intracellular Na+. However, neither the ouabain-sensitive nor the ouabain-insensitive component of Na+ influx altered in SHRSP erythrocytes compared with WKY erythrocytes in paired experiments. Our results do not support the hypothesis that altered Na+ transport, resulting in an increase in erythrocyte Na+ concentration, is associated with spontaneous hypertension. PMID:3611783

  11. Effects of candesartan, an angiotensin II receptor type I blocker, on atrial remodeling in spontaneously hypertensive rats

    PubMed Central

    Choisy, Stéphanie C.; Kim, Shang‐Jin; Hancox, Jules C.; Jones, Sandra A.; James, Andrew F.

    2015-01-01

    Abstract Hypertension‐induced structural remodeling of the left atrium (LA) has been suggested to involve the renin–angiotensin system. This study investigated whether treatment with an angiotensin receptor blocker, candesartan, regresses atrial remodeling in spontaneously hypertensive rats (SHR). Effects of treatment with candesartan were compared to treatment with a nonspecific vasodilatator, hydralazine. Thirty to 32‐week‐old adult male SHR were either untreated (n = 15) or received one of either candesartan cilexetil (n = 9; 3 mg/kg/day) or hydralazine (n = 10; 14 mg/kg/day) via their drinking water for 14 weeks prior to experiments. Untreated age‐ and sex‐matched Wistar‐Kyoto rats (WKY; n = 13) represented a normotensive control group. Untreated SHR were hypertensive, with left ventricular hypertrophy (LVH) compared to WKY, but there were no differences in systolic pressures in excised, perfused hearts. LA from SHR were hypertrophied and showed increased fibrosis compared to those from WKY, but there was no change in connexin‐43 expression or phosphorylation. Treatment with candesartan reduced systolic tail artery pressures of conscious SHR below those of normotensive WKY and caused regression of both LVH and LA hypertrophy. Although hydralazine reduced SHR arterial pressures to those of WKY and led to regression of LA hypertrophy, it had no significant effect on LVH. Notably, LA fibrosis was unaffected by treatment with either agent. These data show that candesartan, at a dose sufficient to reduce blood pressure and LVH, did not cause regression of LA fibrosis in hypertensive rats. On the other hand, the data also suggest that normalization of arterial pressure can lead to the regression of LA hypertrophy. PMID:25626873

  12. Learned helplessness and social avoidance in the Wistar-Kyoto rat

    PubMed Central

    Nam, Hyungwoo; Clinton, Sarah M.; Jackson, Nateka L.; Kerman, Ilan A.

    2014-01-01

    The Wistar-Kyoto (WKY) rat is an established depression model characterized by elevated anxiety- and depression-like behavior across a variety of tests. Here we further characterized specific behavioral and functional domains relevant to depression that are altered in WKY rats. Moreover, since early-life experience potently shapes emotional behavior, we also determined whether aspects of WKYs' phenotype were modifiable by early-life factors using neonatal handling or maternal separation. We first compared WKYs' behavior to that of Sprague–Dawley (SD), Wistar, and Spontaneously Hypertensive (SHR) rats in: the open field test, elevated plus maze, novelty-suppressed feeding test, a social interaction test, and the forced swim test (FST). WKYs exhibited high baseline immobility in the FST and were the only strain to show increased immobility on FST Day 2 vs. Day 1 (an indicator of learned helplessness). WKYs also showed greater social avoidance, along with enlarged adrenal glands and hearts relative to other strains. We next tested whether neonatal handling or early-life maternal separation stress influenced WKYs' behavior. Neither manipulation affected their anxiety- and depressive-like behaviors, likely due to a strong genetic underpinning of their phenotype. Our findings indicate that WKY rats are a useful model that captures specific functional domains relevant to clinical depression including: psychomotor retardation, behavioral inhibition, learned helplessness, social withdrawal, and physiological dysfunction. WKY rats appear to be resistant to early-life manipulations (i.e., neonatal handling) that are therapeutic in other strains, and may be a useful model for the development of personalized anti-depressant therapies for treatment resistant depression. PMID:24744709

  13. Calcium and sodium transport and vitamin D metabolism in the spontaneously hypertensive rat.

    PubMed Central

    Schedl, H P; Miller, D L; Pape, J M; Horst, R L; Wilson, H D

    1984-01-01

    Serum ionized calcium levels are lower and immunoreactive parathyroid hormone levels are higher in the spontaneously hypertensive (SH) rat than in the normotensive Wistar-Kyoto (WKy) control. We postulated that there is either a defect in the regulation of vitamin D metabolism by parathyroid hormone or that the gut target organ for vitamin D in the SH rat is unresponsive. To test these hypotheses we measured serum concentrations of vitamin D metabolites and intestinal transport of calcium and sodium. Compared with that of WKy controls, in vitro calcium transport by duodenal sacs of the SH rat was decreased (P less than 0.001) at 5 wk, before the development of hypertension, and at 12 wk, after hypertension was well established. When measured in vivo in the most proximal 20 cm of small intestine, maximum velocity (Vmax) for calcium transport was decreased (P less than 0.05) and net absorption of sodium and water was increased (P less than 0.05) in SH rats as compared with WKy rats. Vmax for calcium transport was also decreased (P less than 0.05) in the most distal 20 cm of small intestine of SH rats, but net sodium and water transport were the same in SH and WKy rats. At 12 wk, serum concentration of 1,25-dihydroxycholecalciferol [1,25-(OH)2D3] was the same in both SH and WKy groups, but its precursor, 25-hydroxycholecalciferol, was increased (P less than 0.05) in the SH rat. We conclude that in the SH rat: (a) the concentration of 1,25-(OH)2D3 is inappropriately low in relation to the elevated immunoreactive parathyroid hormone and the depressed calcium absorption, suggesting a defect in the regulation of vitamin D metabolism; and (b) the depressed calcium absorption, in the setting of normal concentrations of [1,25-(OH)2D3], demonstrates unresponsiveness of the gut to vitamin D and may explain in part the low serum ionized calcium found in earlier studies. The presence of these abnormalities before we found a significant difference in blood pressure suggests that

  14. Effects of High Fat Feeding on Adipose Tissue Gene Expression in Diabetic Goto-Kakizaki Rats

    PubMed Central

    Xue, Bai; Nie, Jing; Wang, Xi; DuBois, Debra C; Jusko, William J; Almon, Richard R

    2015-01-01

    Development and progression of type 2 diabetes is a complex interaction between genetics and environmental influences. High dietary fat is one environmental factor that is conducive to the development of insulin-resistant diabetes. In the present report, we compare the responses of lean poly-genic, diabetic Goto-Kakizaki (GK) rats to those of control Wistar-Kyoto (WKY) rats fed a high fat diet from weaning to 20 weeks of age. This comparison included a wide array of physiological measurements along with gene expression profiling of abdominal adipose tissue using Affymetrix gene array chips. Animals of both strains fed a high fat diet or a normal diet were sacrificed at 4, 8, 12, 16, and 20 weeks for this comparison. The microarray analysis revealed that the two strains developed different adaptations to increased dietary fat. WKY rats decrease fatty acid synthesis and lipogenic processes whereas GK rats increase lipid elimination. However, on both diets the major differences between the two strains remained essentially the same. Specifically relative to the WKY strain, the GK strain showed lipoatrophy, chronic inflammation, and insulin resistance. PMID:26309393

  15. Spatial memory in spontaneously hypertensive rats (SHR).

    PubMed

    Sontag, Thomas-A; Fuermaier, Anselm B M; Hauser, Joachim; Kaunzinger, Ivo; Tucha, Oliver; Lange, Klaus W

    2013-01-01

    The spontaneously hypertensive rat (SHR) is an established animal model of ADHD. It has been suggested that ADHD symptoms arise from deficits in executive functions such as working memory, attentional control and decision making. Both ADHD patients and SHRs show deficits in spatial working memory. However, the data on spatial working memory deficits in SHRs are not consistent. It has been suggested that the reported cognitive deficits of SHRs may be related to the SHRs' locomotor activity. We have used a holeboard (COGITAT) to study both cognition and activity in order to evaluate the influence of the activity on the cognitive performance of SHRs. In comparison to Wistar-Kyoto (WKY) rats, SHRs did not have any impairment in spatial working memory and reference memory. When the rats' locomotor activity was taken into account, the SHRs' working memory and reference memory were significantly better than in WKY rats. The locomotor activity appears to be a confounding factor in spatial memory tasks and should therefore be controlled for in future studies. In the SHR model of ADHD, we were unable to demonstrate an impairment of working memory which has been reported in patients with ADHD. PMID:24009775

  16. Absence of “Warm-Up” during Active Avoidance Learning in a Rat Model of Anxiety Vulnerability: Insights from Computational Modeling

    PubMed Central

    Myers, Catherine E.; Smith, Ian M.; Servatius, Richard J.; Beck, Kevin D.

    2014-01-01

    Avoidance behaviors, in which a learned response causes omission of an upcoming punisher, are a core feature of many psychiatric disorders. While reinforcement learning (RL) models have been widely used to study the development of appetitive behaviors, less attention has been paid to avoidance. Here, we present a RL model of lever-press avoidance learning in Sprague-Dawley (SD) rats and in the inbred Wistar Kyoto (WKY) rat, which has been proposed as a model of anxiety vulnerability. We focus on “warm-up,” transiently decreased avoidance responding at the start of a testing session, which is shown by SD but not WKY rats. We first show that a RL model can correctly simulate key aspects of acquisition, extinction, and warm-up in SD rats; we then show that WKY behavior can be simulated by altering three model parameters, which respectively govern the tendency to explore new behaviors vs. exploit previously reinforced ones, the tendency to repeat previous behaviors regardless of reinforcement, and the learning rate for predicting future outcomes. This suggests that several, dissociable mechanisms may contribute independently to strain differences in behavior. The model predicts that, if the “standard” inter-session interval is shortened from 48 to 24 h, SD rats (but not WKY) will continue to show warm-up; we confirm this prediction in an empirical study with SD and WKY rats. The model further predicts that SD rats will continue to show warm-up with inter-session intervals as short as a few minutes, while WKY rats will not show warm-up, even with inter-session intervals as long as a month. Together, the modeling and empirical data indicate that strain differences in warm-up are qualitative rather than just the result of differential sensitivity to task variables. Understanding the mechanisms that govern expression of warm-up behavior in avoidance may lead to better understanding of pathological avoidance, and potential pathways to modify these processes. PMID

  17. Vitamin D3 deficiency increases DNA damage and the oxidative burst of neutrophils in a hypertensive rat model.

    PubMed

    Machado, Carla da Silva; Venancio, Vinicius Paula; Aissa, Alexandre Ferro; Hernandes, Lívia Cristina; de Mello, Michela Bianchi; Del Lama, José Eduardo Cavalcanti; Marzocchi-Machado, Cleni Mara; Bianchi, Maria Lourdes Pires; Antunes, Lusânia Maria Greggi

    2016-03-01

    Deficiency of vitamin D3, a lipophilic micronutrient, plays a role in the development of some chronic diseases. Vitamin D3 deficiency affects 25-50% of the human population and has been associated with increased risk for development of hypertension. DNA damage induced by reactive oxygen species (ROS) occurs more often in hypertensive than in normotensive individuals, and vitamin D3 status can influence this relationship. The aim of this study was to evaluate whether a diet supplemented with (10,000 IU/kg) or deficient in (0 IU/kg) vitamin D3, compared to a vitamin D3 control diet (1000 IU/kg), would modulate DNA damage and ROS production in spontaneously hypertensive rats (SHR) and normotensive control Wistar-Kyoto (WKY) rats after 12 weeks of treatment. ROS production was assessed by measuring the oxidative burst of neutrophils. DNA damage was evaluated using the comet assay in peripheral blood and the micronucleus test in bone marrow and peripheral blood. Vitamin D3 supplementation did not induce DNA damage and did not change neutrophil ROS production in SHR and WKY rats. Vitamin D3 deficiency induced neutrophil ROS production and a high frequency of micronucleus formation in the bone marrow and peripheral blood of SHR rats only, and induced DNA damage (comet) in peripheral blood of both SHR and WKY rats. In conclusion, vitamin D3 deficiency showed a more pronounced effect on hypertensive animals. Population studies are needed to test whether this relationship also exists in humans. PMID:26994490

  18. Role of intramitochondrial nitric oxide in rat heart and kidney during hypertension.

    PubMed

    Aguilera-Aguirre, Leopoldo; González-Hernández, Juan Carlos; Pérez-Vázquez, Victoriano; Ramírez, Joel; Clemente-Guerrero, Mónica; Villalobos-Molina, Rafael; Saavedra-Molina, Alfredo

    2002-05-01

    Nitric oxide (NO) is an important reactive molecule in many organisms. A mitochondrial nitric oxide synthase has been described; however, the role of NO in this organelle is not yet fully clear. We tested the effect of intramitochondrial NO on various functions from spontaneously hypertensive rats (SHR) and their normotensive genetic control, Wistar-Kyoto (WKY) rats. While the stimulation of intramitochondrial NOS increased calcium- and phosphate-induced permeability transition pore opening, its inhibition partially prevented it, without affecting membrane potential. Matrix free calcium and the pH decreased with NOS inhibition. Basal [NO] was lower in SHR than in WKY. Our data suggest that intramitochondrial NO plays an important role in mitochondrial regulation during hypertension. PMID:16120294

  19. Methylphenidate Treatment in Adolescent Rats with an Attention Deficit/Hyperactivity Disorder Phenotype: Cocaine Addiction Vulnerability and Dopamine Transporter Function

    PubMed Central

    Harvey, Roxann C; Sen, Sucharita; Deaciuc, Agripina; Dwoskin, Linda P; Kantak, Kathleen M

    2011-01-01

    Appropriate animal models of attention deficit/hyperactivity disorder (ADHD) and drug reinforcement allow investigation of possible underlying biological bases of ADHD and its comorbidity with cocaine addiction. Toward this end, spontaneously hypertensive rats (SHRs) exhibiting an ADHD phenotype were compared with Wistar-Kyoto (WKY) and Wistar (WIS) rats. Initially, 1.5 mg/kg oral methylphenidate or vehicle was administered between postnatal days 28 and 55, and acquisition of visual discrimination learning was examined. After discontinuing adolescent treatments, adult rats were evaluated for cocaine self-administration and dopamine transporter (DAT) function in the prefrontal cortex (PFC) and striatum. During adolescence, SHRs showed deficits in visual discrimination relative to WKY and WIS rats when non-medicated. Methylphenidate improved visual discrimination only in SHRs. Compared with WKY and WIS rats, SHRs with previous methylphenidate treatment acquired cocaine self-administration faster, identified cocaine as a highly efficacious reinforcer by displaying an upward shift in the cocaine dose–response function, and showed the greatest motivation to self-administer cocaine by exhibiting the highest progressive ratio breakpoints. In the PFC, the maximal dopamine uptake (Vmax) at DAT was decreased in SHRs and increased in WKY and WIS rats by previous methylphenidate treatment. The affinity (Km) for dopamine at DAT in the PFC was not different between strains, nor was Vmax or Km altered in the striatum by previous methylphenidate treatment in any strain. Methylphenidate-induced decreases in dopamine clearance by DAT in the PFC may underlie increased cocaine self-administration in SHRs. These preclinical findings suggest that caution should be exercised when methylphenidate is prescribed for first-time treatment of ADHD in adolescent patients, as cocaine addiction vulnerability may be augmented. PMID:21150910

  20. Glial fibrillary acidic protein (GFAP) immunoreactivity correlates with cortical perfusion parameters determined by bolus tracking arterial spin labelling (bt-ASL) magnetic resonance (MR) imaging in the Wistar Kyoto rat.

    PubMed

    Gormley, Shane; Rouine, Jennifer; McIntosh, Allison; Kerskens, Christian; Harkin, Andrew

    2016-06-01

    Alterations in astrocyte number and function have been implicated in the pathophysiology of a number of psychiatric disorders. The development of magnetic resonance imaging (MRI) as a tool in the animal laboratory has enabled an investigation of the relationship between pathological and neuroimaging markers in animal models. However the physiological processes which underlie these markers and their role in mediating behavioural deficits is still poorly understood. Rodent models have provided us with important insights into physiological and cellular mechanisms which may mediate anxiety and depression-related behaviours. The Wistar-Kyoto (WKY) rat is a strain which endogenously expresses highly anxious and depressive-like behaviours and has previously been reported to exhibit alterations in immunoreactivity for the astrocytic marker glial fibrillary acidic protein (GFAP) in brain sub-regions relative to more stress resilient out-bred strains. Here we report that the depressive and anxiety-like behaviours exhibited by the WKY rat strain are associated with alterations in brain morphology including a decrease in hippocampal volume, coupled with reduced resting state frontal cortical perfusion as assessed by MR bolus tracking arterial spin labelling (bt-ASL) relative to the out-bred Wistar strain. Pre-limbic cortical GFAP immunoreactivity and astrocyte cell number were positively correlated with cortical blood perfusion in the WKY strain. These experiments provide a link between pathological and neuroimaging markers of aberrant astrocytic function and add validity to the WKY rat as a model for co-morbid anxiety and depression. PMID:27068181

  1. Training understanding of reversible sentences: a study comparing language-impaired children with age-matched and grammar-matched controls

    PubMed Central

    Hsu, Hsinjen Julie

    2014-01-01

    Introduction. Many children with specific language impairment (SLI) have problems with language comprehension, and little is known about how to remediate these. We focused here on errors in interpreting sentences such as “the ball is above the cup”, where the spatial configuration depends on word order. We asked whether comprehension of such short reversible sentences could be improved by computerized training, and whether learning by children with SLI resembled that of younger, typically-developing children. Methods. We trained 28 children with SLI aged 6–11 years, 28 typically-developing children aged from 4 to 7 years who were matched to the SLI group for raw scores on a test of receptive grammar, and 20 typically-developing children who were matched to the SLI group on chronological age. A further 20 children with SLI were given pre- and post-test assessments, but did not undergo training. Those in the trained groups were given training on four days using a computer game adopting an errorless learning procedure, during which they had to select pictures to correspond to spoken sentences such as “the cup is above the drum” or “the bird is below the hat”. Half the trained children heard sentences using above/below and the other half heard sentences using before/after (with a spatial interpretation). A total of 96 sentences was presented over four sessions. Half the sentences were unique, whereas the remainder consisted of 12 repetitions of each of four sentences that became increasingly familiar as training proceeded. Results. Age-matched control children performed near ceiling (≥ 90% correct) in the first session and were excluded from the analysis. Around half the trained SLI children also performed this well. Training effects were examined in 15 SLI and 16 grammar-matched children who scored less than 90% correct on the initial training session. Overall, children’s scores improved with training. Memory span was a significant predictor of

  2. Cerebrovascular effects of nitric oxide manipulation in spontaneously hypertensive rats

    PubMed Central

    Fouyas, Ioannis P; Kelly, Paul A T; Ritchie, Isobel M; Whittle, Ian R

    1997-01-01

    Evidence that nitric oxide (NO) bioactivity is altered in chronic hypertension is conflicting, possibly as a result of heterogeneity in both the nature of the dysfunction and in the disease process itself. The brain is particularly vulnerable to the vascular complications of chronic hypertension, and the aim of this study was to assess whether differences in the cerebrovascular responsiveness to the NO synthase (NOS) inhibitors, NG-nitro-L-arginine methyl ester (L-NAME) and 7-nitroindazole (7-NI), and to the NO donor 3-morpholinosydnonimine (SIN-1) might indicate one possible source of these complications. Conscious spontaneously hypertensive (SHR) and WKY rats, were treated with L-NAME (30 mg kg−1, i.v.), 7-NI (25 mg kg−1, i.p.), SIN-1 (0.54 or 1.8 mg kg−1 h−1, continuous i.v. infusion) or saline (i.v.), 20 min before the measurement of local cerebral blood flow (LCBF) by the fully quantitative [14C]-iodoantipyrine autoradiographic technique. With the exception of mean arterial blood pressure (MABP), there were no significant differences in physiological parameters between SHR and WKY rats within any of the treatment groups, or between treatment groups. L-NAME treatment increased MABP by 27% in WKY and 18% in SHR groups, whilst 7-NI had no significant effect in either group. Following the lower dose of SIN-1 infusion, MABP was decreased to a similar extent in both groups (around −20%). There was no significant difference in MABP between groups following the higher dose of SIN-1, but this represented a decrease of −41% in SHR and −21% in WKY rats. With the exception of one brain region (nucleus accumbens), there were no significant differences in basal LCBF between WKY and SHR. L-NAME produced similar decreases in LCBF in both groups, ranging between −10 and −40%. The effect of 7-NI upon LCBF was more pronounced in the SHR (ranging from −34 to −57%) compared with the WKY (ranging from −14 to −43%), and in seven out of the

  3. Prepro-thyrotropin releasing hormone 178-199 immunoreactivity is altered in the hypothalamus of the Wistar-Kyoto strain of rat.

    PubMed

    Suzuki, S; Solberg, L C; Redei, E E; Handa, R J

    2001-09-21

    The rat prepro-thyrotropin releasing hormone (TRH) 178-199 is derived from prepro-TRH by the actions of the endopeptidases, prohormone convertase 1 (PC1) and PC2. PPTRH 178-199 attenuates the synthesis and secretion of adrenocorticotropic hormone (ACTH) from the anterior pituitary both in vitro and in vivo, suggesting an inhibitory action on hypothalamic-pituitary-adrenal (HPA) axis function. This peptide also acts centrally to increase activity and decrease anxiety related behaviors. To elucidate the involvement of this peptide in these functions, we have compared the expression of PPTRH 178-199, PPTRH mRNA, and PC1 and PC2 mRNAs in the Wistar-Kyoto (WKY) and Wistar strains of rat. WKY rats have been shown to possess neuroendocrine abnormalities (HPA hyper-activity) and hyper-emotional behavioral characteristics. Immunohistochemical analysis of PPTRH 178-199 demonstrated significant strain differences in the paraventricular nucleus (PVN) of the hypothalamus and the parastrial nucleus (PSN). WKY rats had significantly greater numbers of immunoreactive (IR) cell body profiles (P<0.0005) than Wistar rats in the PVN and a significantly lower fiber density (P<0.002) in the PSN. Levels of PPTRH, PC1, and PC2 mRNA were not different between strains in any brain region examined. These data suggest that altered levels of PPTRH 178-199 in WKY rats could cause, at least in part, the hyper-activity of the HPA axis and the hyper-emotional behavioral characteristics seen in this rat strain. Such data fit with the hypothesis that PPTRH 178-199 is involved in the regulation of the HPA axis and behavior. PMID:11549391

  4. Intraindividual variability (IIV) in an animal model of ADHD - the Spontaneously Hypertensive Rat

    PubMed Central

    2010-01-01

    Attention-deficit/hyperactivity disorder (ADHD) is characterized by numerous behaviors including inattention, hyperactivity and impulsiveness. ADHD-affected individuals also have high intra-individual variability (IIV) in reaction time. The genetic control of IIV is not well understood. The single study of the genetics of this phenomenon in humans detected only marginal associations between genotypes at two candidate genes for ADHD and variability in response time. The Spontaneously Hypertensive Rat (SHR/NCrl) is an animal model of ADHD, expressing high activity, inattention and impulsive behavior during operant and task tests. The SHR might be useful for identifying genes for variability, but it is not known whether it also expresses high IIV, as is symptomatic of ADHD. We therefore conducted an investigation of IIV in the SHR. We used 16 SHR/NCrl rats and 15 Wistar-Kyoto (WKY/Nico) controls applying a reinforcement schedule used in the validation of the SHR as an animal model of ADHD. We represented IIV as the average absolute deviation of individual behavior within the five 18-min segments of each experimental session from the average behavioral trait value within that session ('individual phenotypic dispersion', PDi). PDi for hyperactivity, impulsiveness and inattention in the SHR and WKY rats was analyzed using nonparametric ranking by experimental session. SHR/NCrl rats had higher PDi than WKY/Nico controls for impulsiveness and inattention. There was a significant upward trend for PDi over experimental segments within sessions for attention in SHR rats, but not in WKY. PDi for hyperactivity was correlated with PDi for impulsiveness and we therefore excluded observations associated with short IRTs (< 0.67s); dispersion in hyperactivity outside this interval was also significantly higher in SHR rats than in WKY rats. Some studies indicate the sharing of symptoms of hyperactivity and impulsiveness in SHR and ADHD-affected humans; high IIV in operant behavioral

  5. Clitoria ternatea root extract enhances acetylcholine content in rat hippocampus.

    PubMed

    Rai, K S; Murthy, K D; Karanth, K S; Nalini, K; Rao, M S; Srinivasan, K K

    2002-12-01

    Treatment with 100 mg/kg of Clitoria ternatea aqueous root extract (CTR), for 30 days in neonatal and young adult age groups of rat, significantly increased acetylcholine (ACh) content in their hippocampi as compared to age matched controls. Increase in ACh content in their hippocampus may be the neurochemical basis for their improved learning and memory. PMID:12490229

  6. Age-related changes in hypertensive brain damage in the hippocampi of spontaneously hypertensive rats.

    PubMed

    Li, Yali; Liu, Jian; Gao, Dengfeng; Wei, Jin; Yuan, Haifeng; Niu, Xiaolin; Zhang, Qiaojun

    2016-03-01

    The aim of the present study was to investigate the age‑related alterations in hypertensive brain damage in the hippocampi of spontaneously hypertensive rats (SHR) and the underlying mechanisms. Aging resulted in a significant increase in the number of activated astrocytes and apoptotic cells in the SHR group, which was accompanied by increased expression of oxidative stress markers (iNOS and gp47phox) and apoptotic regulatory proteins (Bax and caspase‑3). In addition, the expression of PPAR‑γ and Bcl‑2 were progressively reduced with increasing age in the SHR group. The 32 and 64‑week‑old SHRs exhibited significantly increased numbers of apoptotic cells, oxidative stress markers and pro‑apoptotic proteins compared with age‑matched WKY rats, which was accompanied by reduced expression of PPAR‑γ. Compared with the 16 and 32‑week‑old WKY group, the 64‑week‑old WKY rats exhibited increased oxidative stress and pro‑apoptotic markers, and increased levels apoptotic cells. In conclusion, the present study indicated that both aging and hypertension enhanced brain damage and oxidative stress injury in the hippocampi of SHRs, indicated by an increased presence of apoptotic cells and astrocytes. In addition, reduced expression of PPAR‑γ may contribute to the age‑related brain damage in SHRs. PMID:26846626

  7. Pharmacological evidence of hypotensive activity of Marrubium vulgare and Foeniculum vulgare in spontaneously hypertensive rat.

    PubMed

    El Bardai, S; Lyoussi, B; Wibo, M; Morel, N

    2001-05-01

    The hypotensive effects of the water extract of Marrubium vulgare L. and Foeniculum vulgare L. were investigated in spontaneously hypertensive rats (SHR) and in normotensive Wistar-Kyoto rats (WKY). Oral administration of Marrubium or Foeniculum extract lowered the systolic blood pressure of SHR but not of WKY. In SHR, Foeniculum but not Marrubium treatment increased water, sodium and potassium excretion. Ex vivo as well as in vitro, Marrubium extract inhibited the contractile responses of rat aorta to noradrenaline and to KCl (100 mM). Inhibition was greater in aorta from SHR compared to WKY and was not affected by the NO synthase inhibitor N-nitro-L-arginine. Vascular effects of Foeniculum extract were less pronounced than those of Marrubium and were blocked by N-nitro-L-arginine. These results indicate that hypotensive activity of Marrubium and Foeniculum extracts seems to be mediated through different pathways: Foeniculum appeared to act mainly as a diuretic and a natriuretic while Marrubium displayed vascular relaxant activity. PMID:11349824

  8. Acute effects of oral or parenteral aspartame on catecholamine metabolism in various regions of rat brain.

    PubMed

    Yokogoshi, H; Wurtman, R J

    1986-03-01

    Hypertensive (SHR) and nonhypertensive [Wistar-Kyoto (WKY); Sprague-Dawley (SD)] strains of rats received the dipeptide sweetener aspartame (200 mg/kg) or, as a positive control, tyrosine (200 mg/kg) by gavage or parenterally, after a brief (2-h) fast. Two hours later, compared with those of saline controls brain levels of the norepinephrine metabolite 3-methoxy-4-hydroxyphenylethylethyleneglycol (MHPG) sulfate were significantly higher in the hypothalamus (WKY), locus coeruleus (SD and SHR) and brain stem (SHR) in tyrosine-treated animals, and in the locus coeruleus (SD) of those given aspartame. Brain norepinephrine levels were also higher, compared with those of saline-treated control rats, in the cerebral cortex (SD and SHR), amygdala (SD) and locus coeruleus (WKY) after tyrosine administration, and in the amygdala (SD) and cerebral cortex (SHR) after aspartame administration. In another study, oral aspartame was found to be at least as effective as the parenterally administered sweetener in raising regional brain levels of tyrosine or MHPG sulfate (i.e., compared with corresponding levels in saline-treated rats). Animals receiving oral aspartame also exhibited higher plasma tyrosine and phenylalanine ratios (i.e., the ratios of their plasma concentrations to the summed concentrations of other large neutral amino acids that compete with them for uptake into the brain), than animals receiving saline. PMID:3950762

  9. The α1 adrenoceptor antagonist prazosin enhances sleep continuity in fear-conditioned Wistar-Kyoto rats

    PubMed Central

    Laitman, Benjamin M.; Gajewski, Nicholas D.; Mann, Graziella L.; Kubin, Leszek; Morrison, Adrian R.; Ross, Richard J.

    2014-01-01

    Fragmentation of rapid eye movement sleep (REMS) is well described in individuals with posttraumatic stress disorder (PTSD) and likely has significant functional consequences. Fear-conditioned rodents may offer an attractive model of the changes in sleep that characterize PTSD. Following fear conditioning (FC), Wistar-Kyoto (WKY) rats, a strain known to be particularly stress-sensitive, have increased REMS fragmentation that can be quantified as a shift in the distribution of REMS episodes towards the more frequent occurrence of sequential REMS (inter-REMS episode interval ≤ 3 min) vs. single REMS (interval > 3 min). The α1 adrenoceptor antagonist prazosin has demonstrated efficacy in normalizing sleep in PTSD. To determine the utility of fear-conditioned WKY rats as a model of sleep disturbances typical of PTSD and as a platform for the development of new treatments, we tested the hypothesis that prazosin would reduce REMS fragmentation in fear-conditioned WKY rats. Sleep parameters and freezing (a standard measure of anxiety in rodents) were quantified at baseline and on days 1, 7, and 14 following FC, with either prazosin (0.01 mg/kg, i.p.) or vehicle injections administered prior to testing in a between-group design. Fear conditioning was achieved by pairing tones with a mild electric foot shock (1.0 mA, 0.5 s). One, 7, and 14 days following FC, prazosin or vehicle was injected, the tone was presented, freezing was measured, and then sleep was recorded from 11 AM to 3 PM. WKY rats given prazosin, compared to those given vehicle, had a lower amount of seq-REMS relative to total REMS time 14 days after FC. They also had a shorter non-REMS latency and fewer non-REMS arousals at baseline and on days 1 and 7 after FC. Thus, in FC rats, prazosin reduced both REMS fragmentation and non-REMS discontinuity. PMID:24246572

  10. Rats with metabolic syndrome resist the protective effects of N-acetyl l-cystein against impaired spermatogenesis induced by high-phosphorus/zinc-free diet.

    PubMed

    Suzuki, Yuka; Ichihara, Gaku; Sahabudeen, Sheik Mohideen; Kato, Ai; Yamaguchi, Takanori; Imanaka-Yoshida, Kyoko; Yoshida, Toshimichi; Yamada, Yoshiji; Ichihara, Sahoko

    2013-11-01

    Consumption of relatively high amounts of processed food can result in abnormal nutritional status, such as zinc deficiency or phosphorus excess. Moreover, hyperphosphatemia and hypozincemia are found in some patients with diabetic nephropathy and metabolic syndrome. The present study investigated the effects of high-phosphorus/zinc-free diet on the reproductive function of spontaneously hypertensive rats/NDmcr-cp (SHR/cp), a model of the metabolic syndrome. We also investigated the effects of antioxidant, N-acetyl-l-cysteine (NAC), on testicular dysfunction under such conditions. Male SHR/cp and control rats (Wistar Kyoto rats, WKY) were divided into three groups; rats fed control diet (P 0.3%, w/w; Zn 0.2%, w/w), high-phosphorus and zinc-deficient diet (P 1.2%, w/w; Zn 0.0%, w/w) with vehicle, or high-phosphorus and zinc-deficient diet with NAC (1.5mg/g/day) for 12 weeks (n=6 or 8 rats/group). The weights of testis and epididymis were significantly reduced by high-phosphate/zinc-free diet in both SHR/cp and WKY. The same diet significantly reduced caudal epididymal sperm count and motility and induced histopathological changes in the testis in both strains. Treatment with NAC provided significant protection against the toxic effects of the diet on testicular function in WKY, but not in SHR/cp. The lack of the protective effects of NAC on impaired spermatogenesis in SHR/cp could be due to the more pronounced state of oxidative stress observed in these rats compared with WKY. PMID:23810784

  11. THE ROLE OF OXIDATIVE STRESS AND MITOCHONDRIA IN PARTICULATE MATTER (PM)-INDUCED CARDIOPULMONARY INJURY IN STROKE PRONE SPONTANEOUSLY HYPERTENSIVE (SHRSP) AND WISTAR KYOTO (WKY) RATS

    EPA Science Inventory

    Epidemiological studies have associated PM exposure with cardiovascular mortality and morbidity, and this effect seems to be enhanced in populations with pre-existing cardiovascular disease. One hypothesis for this exacerbation is that the higher underlying level of oxidative st...

  12. Enhanced Ca(2+)-induced Ca(2+) release from intracellular stores contributes to catecholamine hypersecretion in adrenal chromaffin cells from spontaneously hypertensive rats.

    PubMed

    Segura-Chama, Pedro; López-Bistrain, Patricia; Pérez-Armendáriz, Elia Martha; Jiménez-Pérez, Nicolás; Millán-Aldaco, Diana; Hernández-Cruz, Arturo

    2015-11-01

    Adrenal chromaffin cells (CCs) from spontaneously hypertensive rats (SHRs) secrete more catecholamine (CA) upon stimulation than CCs from normotensive Wistar Kyoto rats (WKY). Unitary CA exocytosis events, both spontaneous and stimulated, were amperometrically recorded from cultured WKY and SHR CCs. Both strains display spontaneous amperometric spikes but SHR CCs produce more spikes and of higher mean amplitude. After a brief stimulation with high K(+) or caffeine which produces voltage-gated Ca(2+) influx or intracellular Ca(2+) release, respectively, more spikes and of greater mean amplitude and unitary charge were recorded in SHR CCs. Consequently, peak cumulative charge was ~2-fold higher in SHR CCs. Ryanodine (10 μM), a specific blocker of the ryanodine receptors reduced depolarization-induced peak cumulative charge by ~10 % in WKY and ~77 % in SHR CCs, suggesting, a larger contribution of Ca(2+)-induced Ca(2+) release to CA exocytosis in SHR CCs. Accordingly, Ca(2+) imaging showed larger [Ca(2+)]i signals induced both by depolarization and caffeine in SHR CCs. Distribution amplitude histograms showed that small amperometric spikes (0-50 pA) are more frequent in WKY than in SHR CCs. Conversely, medium (50-190 pA) and large (190-290 pA) spikes are more numerous in SHR than in WKY CCs. This study reveals that the enhanced CA secretion in SHR CCs results from a combination of (1) larger depolarization-induced Ca(2+) transients, due to a greater Ca(2+)-induced intracellular Ca(2+) release, (2) more exocytosis events per time unit, and (3) a greater proportion of medium and large amperometric spikes probably due to a higher mean CA content per granule. Enhanced CA release by excessive amplification by Ca(2+) induced Ca(2+) release and larger granule catecholamine content contributes to the increased CA plasma levels and vasomotor tone in SHRs. PMID:25791627

  13. Penumbra detection using PWI/DWI mismatch MRI in a rat stroke model with and without comorbidity: comparison of methods

    PubMed Central

    Reid, Emma; Graham, Delyth; Lopez-Gonzalez, M Rosario; Holmes, William M; Macrae, I Mhairi; McCabe, Christopher

    2012-01-01

    Perfusion-diffusion (perfusion-weighted imaging (PWI)/diffusion-weighted imaging (DWI)) mismatch is used to identify penumbra in acute stroke. However, limitations in penumbra detection with mismatch are recognized, with a lack of consensus on thresholds, quantification and validation of mismatch. We determined perfusion and diffusion thresholds from final infarct in the clinically relevant spontaneously hypertensive stroke-prone (SHRSP) rat and its normotensive control strain, Wistar-Kyoto (WKY) and compared three methods for penumbra calculation. After permanent middle cerebral artery occlusion (MCAO) (WKY n=12, SHRSP n=15), diffusion-weighted (DWI) and perfusion-weighted (PWI) images were obtained for 4 hours post stroke and final infarct determined at 24 hours on T2 scans. The PWI/DWI mismatch was calculated from volumetric assessment (perfusion deficit volume minus apparent diffusion coefficient (ADC)-defined lesion volume) or spatial assessment of mismatch area on each coronal slice. The ADC-derived lesion growth provided the third, retrospective measure of penumbra. At 1 hour after MCAO, volumetric mismatch detected smaller volumes of penumbra in both strains (SHRSP: 31±50 mm3, WKY: 22±59 mm3, mean±s.d.) compared with spatial assessment (SHRSP: 36±15 mm3, WKY: 43±43 mm3) and ADC lesion expansion (SHRSP: 41±45 mm3, WKY: 65±41 mm3), although these differences were not statistically significant. Spatial assessment appears most informative, using both diffusion and perfusion data, eliminating the influence of negative mismatch and allowing the anatomical location of penumbra to be assessed at given time points after stroke. PMID:22669479

  14. Metabolic Signatures of Kidney Yang Deficiency Syndrome and Protective Effects of Two Herbal Extracts in Rats Using GC/TOF MS.

    PubMed

    Zhao, Linjing; Wu, Hongbing; Qiu, Mingfeng; Sun, Wei; Wei, Runmin; Zheng, Xiaojiao; Yang, Yiting; Xin, Xue; Zou, Haimiao; Chen, Tianlu; Liu, Jiajian; Lu, Lina; Su, Jing; Ma, Chungwah; Zhao, Aihua; Jia, Wei

    2013-01-01

    Kidney Yang Deficiency Syndrome (KDS-Yang), a typical condition in Chinese medicine, shares similar clinical signs of the glucocorticoid withdrawal syndrome. To date, the underlying mechanism of KDS-Yang has been remained unclear, especially at the metabolic level. In this study, we report a metabolomic profiling study on a classical model of KDS-Yang in rats induced by hydrocortisone injection to characterize the metabolic transformation using gas chromatography/time-of-flight mass spectrometry. WKY1, a polysaccharide extract from Astragalus membranaceus and Lycium barbarum, and WKY2, an aqueous extract from a similar formula containing Astragalus membranaceus, Lycium barbarum, Morinda officinalis, Taraxacum mongolicum, and Cinnamomum cassia presl, were used separately for protective treatments of KDS-Yang. The changes of serum metabolic profiles indicated that significant alterations of key metabolic pathways in response to abrupt hydrocortisone perturbation, including decreased energy metabolism (lactic acid, acetylcarnitine), lipid metabolism (free fatty acids, 1-monolinoleoylglycerol, and cholesterol), gut microbiota metabolism (indole-3-propionic acid), biosynthesis of catecholamine (norepinephrine), and elevated alanine metabolism, were attenuated or normalized with different degrees by the pretreatment of WKY1 or WKY2, which is consistent with the observations in which the two herbal agents could ameliorate biochemical markers of serum cortisone, adrenocorticotropic (ACTH), and urine 17-hydroxycorticosteroids (17-OHCS). PMID:24159348

  15. Metabolic Signatures of Kidney Yang Deficiency Syndrome and Protective Effects of Two Herbal Extracts in Rats Using GC/TOF MS

    PubMed Central

    Zhao, Linjing; Wu, Hongbing; Qiu, Mingfeng; Sun, Wei; Wei, Runmin; Zheng, Xiaojiao; Yang, Yiting; Xin, Xue; Zou, Haimiao; Chen, Tianlu; Liu, Jiajian; Su, Jing; Ma, Chungwah; Jia, Wei

    2013-01-01

    Kidney Yang Deficiency Syndrome (KDS-Yang), a typical condition in Chinese medicine, shares similar clinical signs of the glucocorticoid withdrawal syndrome. To date, the underlying mechanism of KDS-Yang has been remained unclear, especially at the metabolic level. In this study, we report a metabolomic profiling study on a classical model of KDS-Yang in rats induced by hydrocortisone injection to characterize the metabolic transformation using gas chromatography/time-of-flight mass spectrometry. WKY1, a polysaccharide extract from Astragalus membranaceus and Lycium barbarum, and WKY2, an aqueous extract from a similar formula containing Astragalus membranaceus, Lycium barbarum, Morinda officinalis, Taraxacum mongolicum, and Cinnamomum cassia presl, were used separately for protective treatments of KDS-Yang. The changes of serum metabolic profiles indicated that significant alterations of key metabolic pathways in response to abrupt hydrocortisone perturbation, including decreased energy metabolism (lactic acid, acetylcarnitine), lipid metabolism (free fatty acids, 1-monolinoleoylglycerol, and cholesterol), gut microbiota metabolism (indole-3-propionic acid), biosynthesis of catecholamine (norepinephrine), and elevated alanine metabolism, were attenuated or normalized with different degrees by the pretreatment of WKY1 or WKY2, which is consistent with the observations in which the two herbal agents could ameliorate biochemical markers of serum cortisone, adrenocorticotropic (ACTH), and urine 17-hydroxycorticosteroids (17-OHCS). PMID:24159348

  16. Endotoxin-induced acute lung injury is enhanced in rats with spontaneous hypertension.

    PubMed

    Liu, Demeral D; Hsu, Yung Hsiang; Chen, Hsing I

    2007-01-01

    1. Acute lung injury (ALI), or acute respiratory distress syndrome, is a major cause of mortality in endotoxaemia. The present study tested whether the endotoxaemia-induced changes and associated ALI were enhanced in rats with established hypertension and to examine the possible mechanisms involved. 2. Fifty spontaneously hypertensive rats (SHR) and the same number of normotensive Wistar Kyoto (WKY) rats, aged 12-15 weeks, were used. The experiments were performed in conscious, unanaesthetized rats. Endotoxaemia was produced by intravenous lipopolysaccharide (LPS; 10 mg/kg). N(G)-Nitro-L-arginine methyl ester (L-NAME; 10 mg/kg, i.v.), L-N(6)-(1-iminoethyl)-lysine (L-Nil; 5 mg/kg, i.v.) and 3-morpholinosydnonimine (SIN-1; 5 mg/kg, i.v.) were given 5 min before LPS to observe the effects of nitric oxide synthase (NOS) inhibition and nitric oxide (NO) donation. 3. We monitored arterial pressure and heart rate and evaluated ALI by determining the lung weight/bodyweight ratio, lung weight gain, leakage of Evans blue dye, the protein concentration in bronchoalveolar lavage and histopathological examination. Plasma nitrate/nitrite, methyl guanidine, pro-inflammatory cytokines, including tumour necrosis factor-alpha and interleukin-1beta, and lung tissue cGMP were determined. Expression of mRNA for inducible and endothelial NOS was examined using reverse transcription-polymerase chain reaction. 4. Lipopolysaccharide caused systemic hypotension, ALI and increases in plasma nitrate/nitrite, methyl guanidine, pro-inflammatory cytokines and lung cGMP content. The LPS-induced changes were greater in SHR than in WKY rats. Pretreatment with L-NAME or L-Nil attenuated, whereas the NO donor SIN-1 aggravated, the endotoxin-induced changes. 5. In conclusion, rats with genetic hypertension are more susceptible to endotoxaemia and this results in a greater extent of ALI compared with normotensive WKY rats. PMID:17201737

  17. Excess Salt Increases Infarct Size Produced by Photothrombotic Distal Middle Cerebral Artery Occlusion in Spontaneously Hypertensive Rats

    PubMed Central

    Yao, Hiroshi; Nabika, Toru

    2014-01-01

    Cerebral circulation is known to be vulnerable to high salt loading. However, no study has investigated the effects of excess salt on focal ischemic brain injury. After 14 days of salt loading (0.9% saline) or water, spontaneously hypertensive rats (SHR) and normotensive Wistar-Kyoto rats (WKY) were subjected to photothrombotic middle cerebral artery occlusion (MCAO), and infarct volume was determined at 48 h after MCAO: albumin and hemoglobin contents in discrete brain regions were also determined in SHR. Salt loading did not affect blood pressure levels in SHR and WKY. After MCAO, regional cerebral blood flow (CBF), determined with two ways of laser-Doppler flowmetry (one-point measurement or manual scanning), was more steeply decreased in the salt-loaded group than in the control group. In SHR/Izm, infarct volume in the salt-loaded group was 112±27 mm3, which was significantly larger than 77±12 mm3 in the control group (p = 0.002), while the extents of blood-brain barrier disruption (brain albumin and hemoglobin levels) were not affected by excess salt. In WKY, salt loading did not significantly increase infarct size. These results show the detrimental effects of salt loading on intra-ischemic CBF and subsequent brain infarction produced by phototrhombotic MCAO in hypertensive rats. PMID:24816928

  18. Enhanced vasomotion of cerebral arterioles in spontaneously hypertensive rats

    NASA Technical Reports Server (NTRS)

    Lefer, D. J.; Lynch, C. D.; Lapinski, K. C.; Hutchins, P. M.

    1990-01-01

    Intrinsic rhythmic changes in the diameter of pial cerebral arterioles (30-70 microns) in anesthetized normotensive and hypertensive rats were assessed in vivo to determine if any significant differences exist between the two strains. All diameter measurements were analyzed using a traditional graphic analysis technique and a new frequency spectrum analysis technique known as the Prony Spectral Line Estimator. Graphic analysis of the data revealed that spontaneously hypertensive rats (SHR) possess a significantly greater fundamental frequency (5.57 +/- 0.28 cycles/min) of vasomotion compared to the control Wistar-Kyoto normotensive rats (WKY) (1.95 +/- 0.37 cycles/min). Furthermore, the SHR cerebral arterioles exhibited a significantly greater amplitude of vasomotion (10.07 +/- 0.70 microns) when compared to the WKY cerebral arterioles of the same diameter (8.10 +/- 0.70 microns). Diameter measurements processed with the Prony technique revealed that the fundamental frequency of vasomotion in SHR cerebral arterioles (6.14 +/- 0.39 cycles/min) was also significantly greater than that of the WKY cerebral arterioles (2.99 +/- 0.42 cycles/min). The mean amplitudes of vasomotion in the SHR and WKY strains obtained by the Prony analysis were found not to be statistically significant in contrast to the graphic analysis of the vasomotion amplitude of the arterioles. In addition, the Prony system was able to consistently uncover a very low frequency of vasomotion in both strains of rats that was typically less than 1 cycle/min and was not significantly different between the two strains. The amplitude of this slow frequency was also not significantly different between the two strains. The amplitude of the slow frequency of vasomotion (less than 1 cycle/min) was not different from the amplitude of the higher frequency (2-6 cycles/min) vasomotion by Prony or graphic analysis. These data suggest that a fundamental intrinsic defect exists in the spontaneously hypertensive rat

  19. Coconut oil supplementation and physical exercise improves baroreflex sensitivity and oxidative stress in hypertensive rats.

    PubMed

    Alves, Naiane F B; Porpino, Suênia K P; Monteiro, Matheus M O; Gomes, Enéas R M; Braga, Valdir A

    2015-04-01

    The hypothesis that oral supplementation with virgin coconut oil (Cocos nucifera L.) and exercise training would improve impaired baroreflex sensitivity (BRS) and reduce oxidative stress in spontaneously hypertensive rats (SHR) was tested. Adult male SHR and Wistar Kyoto rats (WKY) were divided into 5 groups: WKY + saline (n = 8); SHR + saline (n = 8); SHR + coconut oil (2 mL·day(-1), n = 8); SHR + trained (n = 8); and SHR + trained + coconut oil (n = 8). Mean arterial pressure (MAP) was recorded and BRS was tested using phenylephrine (8 μg/kg, intravenous) and sodium nitroprusside (25 μg·kg(-1), intravenous). Oxidative stress was measured using dihydroethidium in heart and aorta. SHR + saline, SHR + coconut oil, and SHR + trained group showed higher MAP compared with WKY + saline (175 ± 6, 148 ± 6, 147 ± 7 vs. 113 ± 2 mm Hg; p < 0.05). SHR + coconut oil, SHR + trained group, and SHR + trained + coconut oil groups presented lower MAP compared with SHR + saline group (148 ± 6, 147 ± 7, 134 ± 8 vs. 175 ± 6 mm Hg; p < 0.05). Coconut oil combined with exercise training improved BRS in SHR compared with SHR + saline group (-2.47 ± 0.3 vs. -1.39 ± 0.09 beats·min(-1)·mm Hg(-1); p < 0.05). SHR + saline group showed higher superoxide levels when compared with WKY + saline (774 ± 31 vs. 634 ± 19 arbitrary units (AU), respectively; p < 0.05). SHR + trained + coconut oil group presented reduced oxidative stress compared with SHR + saline in heart (622 ± 16 vs. 774 ± 31 AU, p < 0.05). In aorta, coconut oil reduced oxidative stress in SHR compared with SHR + saline group (454 ± 33 vs. 689 ± 29 AU, p < 0.05). Oral supplementation with coconut oil combined with exercise training improved impaired BRS and reduced oxidative stress in SHR. PMID:25659569

  20. Involvement of microRNA214 and transcriptional regulation in reductions in mevalonate pyrophosphate decarboxylase mRNA levels in stroke-prone spontaneously hypertensive rat livers.

    PubMed

    Michihara, Akihiro; Ide, Norie; Mizutani, Yurika; Okamoto, Manami; Uchida, Maya; Matsuoka, Hiroshi; Akasaki, Kenji

    2015-01-01

    Hypocholesterolemia has been epidemiologically identified as one of the causes of stroke (cerebral hemorrhage). We previously reported that lower protein levels of mevalonate pyrophosphate decarboxylase (MPD), which is responsible for reducing serum cholesterol levels in stroke-prone spontaneously hypertensive rats (SHRSP), in the liver were caused by a reduction in mRNA levels. However, the mechanism responsible for reducing MPD expression levels in the SHRSP liver remains unclear. Thus, we compared microRNA (miR)-214 combined with the 3'-untranslated region of MPD mRNA and heterogeneous nuclear RNA (hnRNA) between SHRSP and normotensive Wistar Kyoto rats (WKY). miR-214 levels in the liver were markedly higher in SHRSP than in WKY, whereas hnRNA levels were significantly lower. These results indicate that the upregulation of miR-214 and downregulation of MPD transcription in the liver both play a role in the development of hypocholesterolemia in SHRSP. PMID:26158200

  1. Aortic wall proteomic analysis in spontaneously hypertensive rats with a blood pressure decrease induced by 6-week load-free swimming

    PubMed Central

    FENG, HONG; LI, HAIYING; ZHANG, DERONG; ZHAO, YUNGANG; JIANG, NING; ZHAO, XIAOLING; ZHANG, YU; TAN, JUNZHEN; FANG, WEN; ZHANG, YONG; LIU, WEI

    2015-01-01

    Decreased arterial compliance is one of the earliest detectable manifestations of adverse structural and functional changes within the vessel wall in hypertension. The proteomic approach is a powerful technique to analyze a complex mixture of proteins in various settings. Physical activity level was negatively associated with blood pressure. Sixteen 4-week-old male spontaneously hypertensive rats (SHR) and 16 Wistar-Kyoto (WKY) rats were randomly divided into four groups: i) SHR exercise group, ii) SHR rest group, iii) WKY exercise group and iv) WKY rest group. In the SHR and WKY exercise groups, rats were treated with a 6-week load-free swimming protocol (1 h/day, 5 days/week). The blood pressure of the rats was tested by the CODATM2 single non-invasive blood pressure measurement appliance. After the 6-week swimming protocol, the total aorta excluding abdominal aorta was extracted. The proteins were separated by two-dimensional gel electrophoresis and identified via LC-mass spectrometry (MS)/MS. After 6-week load-free swimming, blood pressure decreased in the SHRs. Compared with sedentary SHRs, 11 spots on the 2D-gel showed a significant difference in exercised SHRs. Nine of these were chosen for further identification. There were 5 upregulated proteins (long-chain specific acyl-CoA dehydrogenase, heat shock protein β-1, isocitrate dehydrogenase subunit α, actin, α cardiac muscle 1 preprotein and calmodulin isoform 2) and 4 downregulated proteins (adipocyte-type fatty acid-binding protein, tubulin β-2C chain, 78 kDa glucose-regulated protein precursor and mimecan). Proteomics is an effective method to identify the target proteins of exercise intervention for hypertension. PMID:26405545

  2. Modulation of enteric neurons by interleukin-6 and corticotropin-releasing factor contributes to visceral hypersensitivity and altered colonic motility in a rat model of irritable bowel syndrome

    PubMed Central

    Buckley, Maria M; O'Halloran, Ken D; Rae, Mark G; Dinan, Timothy G; O'Malley, Dervla

    2014-01-01

    Abstract The search for effective therapeutic strategies for irritable bowel syndrome (IBS) is hampered by an incomplete understanding of its underlying pathophysiology. Stress and altered plasma cytokine profiles indicative of immune activation are characteristic of the disorder. The neuromodulatory effects of interleukin-6 (IL-6) and corticotropin-releasing factor receptor (CRFR) 1 in visceral pain and stress-induced defecation in the Wistar Kyoto (WKY) rat model of IBS were investigated. Sprague Dawley and WKY rats were administered anti-IL-6 receptor antibodies (xIL-6R, 0.5 mg kg−1 i.p) with or without the CRFR1 antagonist antalarmin (10 mg kg−1 i.p). Post-intervention, the pain threshold to colorectal distension and stress-induced faecal output were compared and changes in colonic mucosal protein expression were investigated. The neuro-stimulatory effects of IBS plasma on the myenteric plexus is mediated by IL-6, IL-8 and CRF. The stimulatory effects of these soluble factors on myenteric neuron excitability and colonic contractility were additive. Moreover, inhibition of IL-6 and CRF1 receptors in vivo in the WKY IBS rat model normalized stress-induced defecation (P < 0.01) and visceral pain sensitivity (P < 0.001) with associated changes in protein expression of the tight junction proteins occludin and claudin 2, the visceral pain-associated T-type calcium channel CaV3.2 and intracellular signalling molecules STAT3, SOCS3 and ERK1/2. These studies demonstrate the additive effects of immune and stress factors on myenteric neuronal excitability. Moreover, combined targeting of peripheral IL-6 and CRF1 receptors is effective in alleviating IBS-like symptoms in the WKY rat. Thus, crosstalk between stress and immune factors during IBS flares may underlie symptom exacerbation. PMID:25260633

  3. Stress-reactive rats (high-avoidance female rats) have a shorter lifespan than stress-nonreactive rats (low-avoidance female rats)

    PubMed Central

    Ohta, Ryo; Kumagai, Fumiaki; Marumo, Hideki; Usumi, Kenji; Saito, Yoshiaki; Kuwagata, Makiko

    2015-01-01

    Although Hatano high-avoidance and low-avoidance rats (HAA and LAA, respectively) have been selectively bred for good versus poor avoidance learning, HAA rats are known to be more reactive to stress than LAA rats. In this study, HAA and LAA female rats were compared during reproductive aging by observing estrous cycles from 8 to 11 months of age. Furthermore, these rats were allowed to live out their natural lifespans, that is, until 24 months of age, in order to compare their survival and to clarify the relationship between reproductive aging and tumor development. At eight months of age, 2 of 35 HAA rats and 20 of 35 LAA rats had abnormal estrous cycles. The median lifespan of the HAA rats (673 days) was shorter than that of the LAA rats (733 days). The incidence of pituitary neoplasia was higher in the HAA rats than in the LAA rats. These results suggest that HAA female rats (i.e., stress-reactive rats) have a shorter lifespan than LAA female rats (i.e., stress-nonreactive rats) and develop pituitary neoplasia, which was one of the causal factors in their accelerated mortality. However, the onset of an age-matched abnormal cycle did not correspond with their lifespan. PMID:27182111

  4. Early life stress induces renal dysfunction in adult male rats but not female rats

    PubMed Central

    Loria, Analia S.; Yamamoto, Tatsuo; Pollock, Jennifer S.

    2013-01-01

    Maternal separation (MatSep) is a model of behavioral stress during early life. We reported that MatSep exacerbates ANG II-induced hypertension in adult male rats. The aims of this study were to determine whether exposure to MatSep in female rats sensitizes blood pressure to ANG II infusion similar to male MatSep rats and to elucidate renal mechanisms involved in the response in MatSep rats. Wistar Kyoto (WKY) pups were exposed to MatSep 3 h/day from days 2 to 14, while control rats remained with their mothers. ANG II-induced mean arterial pressure (MAP; telemetry) was enhanced in female MatSep rats compared with control female rats but delayed compared with male MatSep rats. Creatinine clearance (Ccr) was reduced in male MatSep rats compared with control rats at baseline and after ANG II infusion. ANG II infusion significantly increased T cells in the renal cortex and greater histological damage in the interstitial arteries of male MatSep rats compared with control male rats. Plasma testosterone was greater and estradiol was lower in male MatSep rats compared with control rats with ANG II infusion. ANG II infusion failed to increase blood pressure in orchidectomized male MatSep and control rats. Female MatSep and control rats had similar Ccr, histological renal analysis, and sex hormones at baseline and after ANG II infusion. These data indicate that during ANG II-induced hypertension, MatSep sensitizes the renal phenotype in male but not female rats. PMID:23174859

  5. Mechanism of action of the inhibitory effect of nifedipine on the growth of cultured aortic cells from spontaneously hypertensive and normotensive rats.

    PubMed Central

    Hérembert, T; Zhu, D L; Marche, P

    1995-01-01

    1. To gain insight into the parameters which control vascular structure, we investigated the mechanisms whereby nifedipine, and other dihydropyridines, inhibit the growth of cultured fibroblasts isolated from the adventitia of the aorta of spontaneously hypertensive (SHR) and normotensive Wistar Kyoto (WKY) rats. 2. The effects of nifedipine on cell proliferation and on serum-induced DNA synthesis were determined by measuring the cell number and the incorporation of [3H]-thymidine, respectively. The mechanism of action of nifedipine was studied by adding the drug either to randomly growing cells or to quiescent, G0/G1 arrested and synchronized cells. The effects of varying the duration of drug treatment were also examined. 3. In randomly growing cultures nifedipine, like other dihydropyridines concentration-dependently inhibited cell proliferation; the rank order of effect (measured at a concentration of 10 microM) was nifedipine > nisoldipine > nitrendipine approximately nimodipine. 4. In G0/G1 arrested cell cultures, nifedipine concentration-dependently inhibited serum-induced [3H]-thymidine incorporation. In this respect it had similar effects in cell cultures from WKY and SHR. In both SHR and WKY cultures, nifedipine delayed the transition from G0/G1 to S phase, and inhibited serum-induced DNA synthesis possibly by acting on the early G1 phase. 5. In cell cultures from both SHR and WKY, serum-induced DNA synthesis was similarly (approximately 40%) inhibited after a 1 day treatment with 10 microM nifedipine. In contrast, after 5 days treatment with the drug, the inhibition of DNA synthesis was approximately 65% and approximately 10% in SHR and WKY cultures, respectively.(ABSTRACT TRUNCATED AT 250 WORDS) PMID:7541285

  6. Effect of renal sympathetic nerve on adrenergically and angiotensin II-induced renal vasoconstriction in normal Wistar-Kyoto rats

    PubMed Central

    2011-01-01

    Background This study examined the effect of renal sympathetic innervation on adrenergically and angiotensin II (Ang II)-induced renal vasoconstriction in Wistar-Kyoto (WKY) rats. Methods Forty-eight WKY rats were treated with either losartan (10 mg/kg/day p.o.) or carvedilol (5 mg/kg/day p.o.) or a combination of them (10 mg/kg/day + 5 mg/kg/day p.o.) for 7 days. On day 8, the rats were anaesthetized, and renal vasoconstrictor experiments were carried out. A group of rats was subjected to acute unilateral renal denervation during the acute study. Changes in the renal vasoconstrictor responses were determined in terms of reductions in renal blood flow caused by Ang II, noradrenaline (NA), and methoxamine (ME). Results In normal animals, losartan decreased (P < 0.05) the renal vasoconstrictor response to Ang II but not to NA or ME. Carvedilol treatment, however, blunted (P < 0.05) the renal vasoconstrictor responses to Ang II and adrenergic agonists. Combination of losartan and carvedilol blunted (P < 0.05) the renal vasoconstrictor response to Ang II but augmented the responses to NA and ME (all P < 0.05). Interestingly, when denervated rats were treated with the same combination, there was a reduction (P < 0.05) in the renal vasoconstrictor responses to Ang II and adrenergic agonists. Conclusions Data suggest that the renal sympathetic nerve contributes to adrenergic agonist-mediated renal vasoconstrictions in normal rats. The data further indicate an interactive relationship between renin-angiotensin and sympathetic nervous systems in modulating adrenergically and Ang II-induced renal vasoconstriction in WKY rats. PMID:21047287

  7. The isolated working heart model in infarcted rat hearts.

    PubMed

    Itter, G; Jung, W; Schoelkens, B A; Linz, W

    2005-04-01

    Congestive heart failure (CHF) is one of the most common causes of death in western countries. The aim of this study was to establish and validate the working heart model in rat hearts with CHF. In the rat model the animals show parameters and symptoms that can be extrapolated to the clinical situation of patients with end-stage heart failure. The focus of attention was the evaluation of cardiodynamics (e.g.contractility) in the isolated 'working heart' model. The geometric properties of the left ventricle were measured by planimetry (stereology). Formulae available in the past for determining certain parameters in the working heart model (e.g.external heart work) have to be fitted to the circumstances of the infarcted rat hearts with its different organ properties.CHF was induced in Wistar Kyoto (WKY/NHsd) and spontaneously hypertensive rats (SHR/NHsd) by creating a permanent (8 week) occlusion of the left coronary artery, 2 mm distal to the origin from the aorta, by a modified technique (Itter et al. 2004). This resulted in a large infarction of the free left ventricular wall. We were able to establish and adapt a new and predictive working heart model in spontaneously hypertensive rat hearts with myocardial infarction (MI) 8-12 weeks after coronary artery ligation. At this stage the WKY rat did not show any symptoms of CHF. The SHR rat represented characteristic parameters and symptoms that could be extrapolated to the clinical situation of patients with end-stage heart failure (NYHA III-IV). Upon inspection, severe clinical symptoms of CHF such as dyspnoea, subcutaneous oedema, palebluish limbs and impaired motion were prominent. On necropsy the SHR showed lung oedema, hydrothorax, large dilated left and right ventricular chambers and hypertrophy of the septum. In the working heart model the infarcted animals showed reduced heart power, diminished contractility and enhanced heart work, much more so in the SHR/NHsd than in the Wistar Kyoto rat (WKY/NHsd). The

  8. Reduced activity of SKC a and Na-K ATPase underlies the accelerated impairment of EDH-type relaxations in mesenteric arteries of aging spontaneously hypertensive rats.

    PubMed

    Kong, Billy W C; Man, Ricky Y K; Gao, Yuansheng; Vanhoutte, Paul M; Leung, Susan W S

    2015-06-01

    Aging is accompanied by endothelial dysfunction due to reduced bioavailability of nitric oxide (NO) and/or reduced endothelium-dependent hyperpolarizations (EDH). This study examines the hypothesis that hypertension aggravates the impairment of EDH-type relaxation due to aging. EDH-type relaxations were studied in superior mesenteric arteries isolated from Wistar Kyoto (WKY) and spontaneously hypertensive (SHR) rats of 12, 36, 60, and 72 weeks of age. EDH-type relaxations in WKY were reduced with aging, and this was associated with an impairment of the function of small-conductance calcium-activated potassium channels (SKC a) and sodium-potassium ATPase (Na-K ATPase). EDH-type relaxation in SHR was smaller than that in WKY arteries, and further reduction occurred with aging. Pharmacological experiments suggested a reduced involvement of SKC a and Na-K ATPase and activation of adenosine monophosphate-activated protein kinase and silent information regulator T1 (sirtuin-1; SIRT1) in mesenteric arteries of 12-week-old SHR. These pharmacological findings suggest that in superior mesenteric arteries of the rat, the reduction in EDH-type relaxation occurs with aging and that such a reduction is exacerbated in hypertension. The latter exacerbation appears to involve proteins associated with the process of cellular senescence and is related to impaired function of SKC a and Na-K ATPase, a phenomenon that is also observed in mesenteric arteries of older normotensive rats. PMID:26171229

  9. A simple behavioral paradigm to measure impulsive behavior in an animal model of attention deficit hyperactivity disorder (ADHD) of the spontaneously hypertensive rats.

    PubMed

    Kim, Pitna; Choi, Inha; Pena, Ike Campomayor Dela; Kim, Hee Jin; Kwon, Kyung Ja; Park, Jin Hee; Han, Seol-Heui; Ryu, Jong Hoon; Cheong, Jae Hoon; Shin, Chan Young

    2012-01-01

    Impulsiveness is an important component of many psychiatric disorders including Attention-deficit/hyperactivity disorder (ADHD). Although the neurobiological basis of ADHD is unresolved, behavioral tests in animal models have become indispensable tools for improving our understanding of this disorder. In the punishment/extinction paradigm, impulsivity is shown by subjects that persevere with responding despite punishment or unrewarded responses. Exploiting this principle, we developed a new behavioral test that would evaluate impulsivity in the most validated animal model of ADHD of the Spontaneously Hypertensive rat (SHR) as compared with the normotensive "control" strain, the Wistar Kyoto rat (WKY). In this paradigm we call the Electro-Foot Shock aversive water Drinking test (EFSDT), water-deprived rats should pass over an electrified quadrant of the EFSDT apparatus to drink water. We reasoned that impulsive animals show increased frequency to drink water even with the presentation of an aversive consequence (electro-shock). Through this assay, we showed that the SHR was more impulsive than the WKY as it demonstrated more "drinking attempts" and drinking frequency. Methylphenidate, the most widely used ADHD medication, significantly reduced drinking frequency of both SHR and WKY in the EFSDT. Thus, the present assay may be considered as another behavioral tool to measure impulsivity in animal disease models, especially in the context of ADHD. PMID:24116285

  10. Expression and localization of calmodulin-related proteins in brain, heart and kidney from spontaneously hypertensive rats.

    PubMed

    Kameshima, Satoshi; Okada, Muneyoshi; Yamawaki, Hideyuki

    2016-01-15

    Blood pressure is regulated not only by peripheral arterial resistance, but also by heart, kidney, and central nervous system. We have previously demonstrated that expression level of calmodulin-related proteins including eukaryotic elongation factor 2 kinase (eEF2K), death-associated protein kinase (DAPK)3, and histone deacetylase (HDAC)4 was specifically elevated in mesenteric artery from spontaneously hypertensive rats (SHR), which partly contributes to the development of hypertension via vascular inflammation and structural remodeling. We tested the hypothesis whether expression and localization of eEF2K, DAPK3, and HDAC4 are altered in brain, heart, and kidney from SHR. After brain, left ventricles (LV), and kidney were isolated from 12-week-old male Wistar Kyoto rats (WKY) and SHR, Western blotting and histological analysis were performed. In brain tissue, protein expression of eEF2K and HDAC4 was abundant, whereas DAPK3 protein was less. HDAC4 protein expression in SHR brain was significantly higher than that in WKY brain. In LV, protein expression of eEF2K was relatively higher than DAPK3 or HDAC4, and it was significantly higher in SHR than WKY. In kidney tissue, protein expression of DAPK3 was the highest and seemed to be localized specifically to renal tubule. The present results indicate that the increased HDAC4 in brain and increased eEF2K in LV might be at least in part related to the development of hypertension. PMID:26697749

  11. Effects of dopamine agents on a schedule-induced polydipsia procedure in the spontaneously hypertensive rat and in Wistar control rats.

    PubMed

    Íbias, Javier; Miguéns, Miguel; Pellón, Ricardo

    2016-09-01

    The spontaneously hypertensive rat (SHR) has been proposed as an animal model for attention deficit hyperactivity disorder (ADHD), and typically develops excessive patterns of response under most behavioural protocols. Schedule-induced polydipsia (SIP) is the excessive water consumption that occurs as a schedule effect when food is intermittently delivered and animals are partially food- but not water-deprived. SIP has been used as a model of excessive behaviour, and considerable evidence has involved the dopaminergic system in its development and maintenance. The aim of this study was to evaluate the effects of the most common psychostimulants used in ADHD treatment on SIP, comparing their effects in SHRs with rats from control populations. SHR, Wistar Kyoto (WKY) and Wistar rats were submitted to a multiple fixed time (FT) food schedule with two components: 30 s and 90 s. The acute effects of different dopaminergic compounds were evaluated after 40 sessions of SIP acquisition. All animals showed higher adjunctive drinking under FT 30 s than FT 90 s, and SHRs displayed higher asymptotic SIP levels in FT 90 s compared to WKY and Wistar rats. SHRs were less sensitive to dopaminergic agents than control rats in terms of affecting rates of adjunctive drinking. These differences point to an altered dopaminergic system in the SHR and provide new insights into the neurobiological basis of ADHD pharmacological treatments. PMID:27296274

  12. Whole body plethysmography reveals differential ventilatory responses to ozone in rat models of cardiovascular disease.

    PubMed

    Dye, Janice A; Ledbetter, Allen D; Schladweiler, Mette C; Costa, Daniel L; Kodavanti, Urmila P

    2015-01-01

    To elucidate key factors of host susceptibility to air pollution, healthy and cardiovascular (CV)-compromised rats were exposed to air or ozone (O3) at 0.25, 0.5, or 1.0 ppm for 4 h. We hypothesized that rat strains with the least cardiac reserve would be most prone to develop significant health effects. Using flow whole body plethysmography (FWBP), ventilatory responses in healthy 3-month-old male rats [i.e. Wistar-Kyoto (WKY), Wistar (WIS), and Sprague-Dawley (SD) strains] were compared with hypertensive [i.e. spontaneously hypertensive (SH), fawn-hooded-hypertensive (FHH), and SH-stroke-prone (SHSP)] strains and obese [i.e. SH-heart failure-prone (SHHF) and JCR:LA-cp, atherosclerosis-prone (JCR)] strains. SH were slower to acclimate to the FWBP chambers. At 0-h post-air-exposure, SHSP and SHHF exhibited hyperpnea, indicative of cardiopulmonary insufficiency. At 0-h-post-O3, all but one strain showed significant concentration-dependent decreases in minute volume [MV = tidal volume (TV) × breathing frequency]. Comparing air with 1.0 ppm responses, MV declined 20-27% in healthy, 21-42% in hypertensive, and 33% in JCR rats, but was unchanged in SHHF rats. Penh increased significantly in all strains, with disproportionate increases in "responder" WKY and FHH strains. By 20 h, most changes had resolved, although Penh remained elevated in WKY, SH, and SHSP. Based on the effective dose estimates (O3 ppm × h × MV), the most CV-compromised (SHSP and SHHF) strains received significantly greater O3 lung deposition (25% and 40%, respectively). Data support epidemiologic associations that individuals with cardiopulmonary insufficiency are at greater risk for urban pollutant exposure due, in part, to enhanced lung deposition and exacerbation of hypoxia and pathophysiologic processes of heart failure. PMID:26667328

  13. A comparative autoradiography study in post mortem whole hemisphere human brain slices taken from Alzheimer patients and age-matched controls using two radiolabelled DAA1106 analogues with high affinity to the peripheral benzodiazepine receptor (PBR) system.

    PubMed

    Gulyás, Balázs; Makkai, Boglárka; Kása, Péter; Gulya, Károly; Bakota, Lidia; Várszegi, Szilvia; Beliczai, Zsuzsa; Andersson, Jan; Csiba, László; Thiele, Andrea; Dyrks, Thomas; Suhara, Tetsua; Suzuki, Kazutoshi; Higuchi, Makato; Halldin, Christer

    2009-01-01

    The binding of two radiolabelled analogues (N-(5-[125I]Iodo-2-phenoxyphenyl)-N-(2,5-dimethoxybenzyl)acetamide ([125I]desfluoro-DAA1106) and N-(5-[125I]Fluoro-2-phenoxyphenyl)-N-(2-[125I]Iodo-5-methoxybenzyl)acetamide ([125I]desmethoxy-DAA1106) of the peripheral benzodiazepine receptor (PBR) (or TSPO, 18kDa translocator protein) ligand DAA1106 was examined by in vitro autoradiography on human post mortem whole hemisphere brain slices obtained from Alzheimer's disease (AD) patients and age-matched controls. Both [(125)I]desfluoro-IDAA1106 and [(125)I]desmethoxy-IDAA1106 were effectively binding to various brain structures. The binding could be blocked by the unlabelled ligand as well as by other PBR specific ligands. With both radiolabelled compounds, the binding showed regional inhomogeneity and the specific binding values proved to be the highest in the hippocampus, temporal and parietal cortex, the basal ganglia and thalamus in the AD brains. Compared with age-matched control brains, specific binding in several brain structures (temporal and parietal lobes, thalamus and white matter) in Alzheimer brains was significantly higher, indicating that the radioligands can effectively label-activated microglia and the up-regulated PBR/TSPO system in AD. Complementary immunohistochemical studies demonstrated reactive microglia activation in the AD brain tissue and indicated that increased ligand binding coincides with increased regional microglia activation due to neuroinflammation. These investigations yield further support to the PBR/TSPO binding capacity of DAA1106 in human brain tissue, demonstrate the effective usefulness of its radio-iodinated analogues as imaging biomarkers in post mortem human studies, and indicate that its radiolabelled analogues, labelled with short half-time bioisotopes, can serve as prospective in vivo imaging biomarkers of activated microglia and the up-regulated PBR/TSPO system in the human brain. PMID:18984021

  14. DESIPRAMINE BLOCKS ALCOHOL-INDUCED ANXIETY- AND DEPRESSIVE-LIKE BEHAVIORS IN TWO RAT STRAINS

    PubMed Central

    GETACHEW, BRUK; HAUSER, SHEKETHA R.; TAYLOR, ROBERT E.; TIZABI, YOUSEF

    2011-01-01

    Epidemiological studies indicate significant co-morbid expression of alcoholism, anxiety, and depression. These symptoms are often under-diagnosed and under-treated and can worsen prognostic and treatment outcome for alcoholism. Nonetheless, a causal relationship between alcoholism and these conditions is yet to be established. In this study we sought to determine the effects of daily alcohol administration on the indices of anxiety and depression in two rat strains, one of which exhibits inherent depressive-like characteristics. Moreover, it was of relevance to examine the effects of a clinically useful antidepressant on alcohol-induced behavioral changes. Wistar-Kyoto (WKY) rats derived from Wistar stock show low levels of locomotor activity in an open field and high levels of immobility in the forced swim test (FST) which is considered a measure of their helplessness and hence are considered a putative animal model of depression. Adult female WKY and Wistar rats were exposed for 3 hrs daily to 95% ethanol vapor to achieve a mean blood alcohol level (BAL) of approximately 150 mg/dL. Controls were exposed to air in similar inhalation chambers. Sixteen to 18 hrs following 7 or 14 days of exposure to alcohol, locomotor activity (LCA) in open field, duration of time spent in the open arm of the elevated plus-maze (EPM), reflective of anxiety-like behavior and immobility in FST were evaluated. Alcohol exposure for 7 or 14 days reduced LCA only in Wistar rats but enhanced FST immobility in both strains at both time points. Only 14 day alcohol exposure reduced EPM open arm time in both WKY and Wistar rats. Daily treatment with desipramine (8 mg/kg) blocked all the changes induced by alcohol in both strains. Thus, subchronic (7 day) exposure to alcohol induces depressive-like characteristics in Wistar rats and exacerbates that of WKY rats. Chronic (14 day) exposure, however, also induces an anxiety-like effect in both strains. The depressive-and anxiety-like behaviors

  15. Cerium Dioxide Nanoparticle Exposure Improves Microvascular Dysfunction and Reduces Oxidative Stress in Spontaneously Hypertensive Rats

    PubMed Central

    Minarchick, Valerie C.; Stapleton, Phoebe A.; Sabolsky, Edward M.; Nurkiewicz, Timothy R.

    2015-01-01

    The elevated production of reactive oxygen species (ROS) in the vascular wall is associated with cardiovascular diseases such as hypertension. This increase in oxidative stress contributes to various mechanisms of vascular dysfunction, such as decreased nitric oxide bioavailability. Therefore, anti-oxidants are being researched to decrease the high levels of ROS, which could improve the microvascular dysfunction associated with various cardiovascular diseases. From a therapeutic perspective, cerium dioxide nanoparticles (CeO2 NP) hold great anti-oxidant potential, but their in vivo activity is unclear. Due to this potential anti-oxidant action, we hypothesize that injected CeO2 NP would decrease microvascular dysfunction and oxidative stress associated with hypertension. In order to simulate a therapeutic application, spontaneously hypertensive (SH) and Wistar-Kyoto (WKY) rats were intravenously injected with either saline or CeO2 NP (100 μg suspended in saline). Twenty-four hours post-exposure mesenteric arteriolar reactivity was assessed via intravital microscopy. Endothelium-dependent and –independent function was assessed via acetylcholine and sodium nitroprusside. Microvascular oxidative stress was analyzed using fluorescent staining in isolated mesenteric arterioles. Finally, systemic inflammation was examined using a multiplex analysis and venular leukocyte flux was counted. Endothelium-dependent dilation was significantly decreased in the SH rats (29.68 ± 3.28%, maximal response) and this microvascular dysfunction was significantly improved following CeO2 NP exposure (43.76 ± 4.33%, maximal response). There was also an increase in oxidative stress in the SH rats, which was abolished following CeO2 NP treatment. These results provided evidence that CeO2 NP act as an anti-oxidant in vivo. There were also changes in the inflammatory profile in the WKY and SH rats. In WKY rats, IL-10 and TNF-α were increased following CeO2 NP treatment. Finally, leukocyte

  16. Nuclear orphan receptor Nor-1 contributes to depressive behavior in the Wistar-Kyoto rat model of depression.

    PubMed

    Schaffer, Daniel J; Tunc-Ozcan, Elif; Shukla, Pradeep K; Volenec, Andreja; Redei, Eva E

    2010-11-29

    The current study explored the effects of prolonged antidepressant treatment on mRNA levels of two nuclear receptors in specific brain regions of an animal model of depression, the Wistar-Kyoto (WKY) rat. Both nuclear receptors have been implicated in the development or treatment of depression. The expression of nuclear orphan receptor-1 (Nor-1), a member of the NR4A nuclear orphan receptor family, is induced by electroconvulsive shock, an effective treatment for depression. Deficit in the levels or function of the glucocorticoid receptor (GR) found in depressed patients has been causally implicated in depression, as this deficit is normalized by antidepressant treatments. Baseline levels of amygdalar Nor-1 and GR mRNA were higher in the WKYs compared to the comparison control Sprague-Dawley rats (SD). Prolonged treatment with the antidepressant desipramine (DMI) decreased the expression of both transcripts in the WKY strain concomitantly with decreased immobility in the forced swim test (FST) of depressive behavior. Using short hairpin RNA (shRNA) targeted against Nor-1, we investigated the direct contribution of elevated Nor-1 expression in the amygdala of WKY to their exaggerated depressive behavior in the FST. After validating the shRNA targeting of Nor-1 in vitro, Nor-1 shRNA containing vector was infused intracerebroventricularly, using a linear polyethylenimine (PEI)-containing in vivo gene delivery system. Repeated administration of Nor-1 shRNA ameliorated the depressive behavior of WKYs in the FST and decreased amygdalar Nor-1 mRNA levels without affecting GR mRNA levels. These data demonstrate that brain region-specific changes in GR expression in response to DMI are strain dependent and that elevated amygdalar Nor-1 expression can contribute to depressive behavior in the WKY model of depression. PMID:20851110

  17. Role of heme oxygenase in modulating endothelial function in mesenteric small resistance arteries of spontaneously hypertensive rats.

    PubMed

    Porteri, Enzo; Rodella, Luigi F; Rezzani, Rita; Rizzoni, Damiano; Paiardi, Silvia; de Ciuceis, Carolina; Boari, Gianluca E M; Foglio, Eleonora; Favero, Gaia; Rizzardi, Nicola; Platto, Caterina; Agabiti Rosei, Enrico

    2009-10-01

    It has been proposed that endothelial dysfunction is due to the excessive degradation of nitric oxide (NO) by oxidative stress. The enzyme heme-oxygenase (HO) seems to exert a protective effect on oxidative stress in the vasculature, both in animal models and in humans. The objective of this study is to evaluate the effects of inhibition or activation of HO on endothelial function in mesenteric small resistance arteries of spontaneously hypertensive rats (SHR). Six SHR were treated with cobalt protoporphyrin IX 50 mg/Kg (CoPP), an activator of HO; six SHR with stannous mesoporphyrin 30 mg/Kg (SnMP), an inhibitor of HO, and six SHR with saline. As controls, six Wistar-Kyoto rats (WKY) were treated with CoPP, six WKY with SnMP, and six WKY with saline. Drugs were injected in the peritoneum once a week for 2 weeks. Systolic blood pressure (SBP) was measured (tail cuff method) before and after treatment. Mesenteric small resistance arteries were mounted on a micromyograph. Endothelial function was evaluated as a cumulative concentration-response curve to acetylcholine (ACH), before and after preincubation with N(G)-methyl-L-arginine (L-NMMA, inhibitor of NO synthase), and to bradykinin (BK). In SHR treatment with CoPP, improved ACH-and BK-induced vasodilatation (ANOVA p < 0.001) and this improvement was abolished by L-NMMA (ANOVA p < 0.001). SnMP was devoid of effects on endothelial function. In WKY, both activation and inhibition of HO did not substantially affect endothelium-mediated vasodilatation. The stimulation of HO seems to induce an improvement of endothelial dysfunction in SHR by possibly reducing oxidative stress and increasing NO availability. PMID:19886854

  18. Consistent Pulmonary and Systemic Responses from Inhalation of Fine Concentrated Ambient Particles: Roles of Rat Strains Used and Physicochemical Properties

    PubMed Central

    Kodavanti, Urmila P.; Schladweiler, Mette C.; Ledbetter, Allen D.; McGee, John K.; Walsh, Leon; Gilmour, Peter S.; Highfill, Jerry W.; Davies, David; Pinkerton, Kent E.; Richards, Judy H.; Crissman, Kay; Andrews, Debora; Costa, Daniel L.

    2005-01-01

    Several studies have reported health effects of concentrated ambient particles (CAP) in rodents and humans; however, toxicity end points in rodents have provided inconsistent results. In 2000 we conducted six 1-day exposure studies where spontaneously hypertensive (SH) rats were exposed to filtered air or CAPs (≤ 2.5 μm, 1,138–1,765 μg/m3) for 4 hr (analyzed 1–3 hr afterward). In seven 2-day exposure studies in 2001, SH and Wistar Kyoto (WKY) rats were exposed to filtered air or CAP (≤ 2.5 μm, 144–2,758 μg/m3) for 4 hr/day × 2 days (analyzed 1 day afterward). Despite consistent and high CAP concentrations in the 1-day exposure studies, no biologic effects were noted. The exposure concentrations varied among the seven 2-day exposure studies. Except in the first study when CAP concentration was highest, lavageable total cells and macrophages decreased and neutrophils increased in WKY rats. SH rats demonstrated a consistent increase of lavage fluid γ -glutamyltransferase activity and plasma fibrinogen. Inspiratory and expiratory times increased in SH but not in WKY rats. Significant correlations were found between CAP mass (microgram per cubic meter) and sulfate, organic carbon, or zinc. No biologic effects correlated with CAP mass. Despite low chamber mass in the last six of seven 2-day exposure studies, the levels of zinc, copper, and aluminum were enriched severalfold, and organic carbon was increased to some extent when expressed per milligram of CAP. Biologic effects were evident in those six studies. These studies demonstrate a pattern of rat strain–specific pulmonary and systemic effects that are not linked to high mass but appear to be dependent on CAP chemical composition. PMID:16263512

  19. Farnesyl pyrophosphate synthase inhibitor, ibandronate, improves endothelial function in spontaneously hypertensive rats.

    PubMed

    Han, Jie; Jiang, Dong-Mei; Ye, Yang; Du, Chang-Qing; Yang, Jian; Hu, Shen-Jiang

    2016-05-01

    Reactive oxygen species (ROS), originating predominantly from vascular smooth muscle cells (VSMCs), lead to vascular damage and endothelial dysfunction in rats with hypertension. The downstream signaling pathways of farnesyl pyrophosphate (FPP) synthase, Ras-related C3 botulinum toxin substrate 1 (Rac1) and nicotinamide adenine dinucleotide phosphate (NADPH) oxidase, mediate the generation of ROS. The present study investigated the effect of the FPP synthase inhibitor, ibandronate, on ROS production, the possible beneficial effect on endothelial dysfunction and the underlying mechanisms in spontaneously hypertensive rats (SHRs). The SHRs were treated with ibandronate for 30 days. Endothelium‑dependent and independent vasorelaxation were measured in isolated aortic rings. Additionally, VSMCs from the SHRs and Wistar‑Kyoto (WKY) rats were cultured. The production of ROS and activation of NADPH oxidase were determined using fluorescence and chemiluminescence, respectively, in vivo and in vitro. Angiotensin II (Ang II) increased ROS production in the cultured VSMCs from the WKY rats and SHRs, in a concentration‑dependent manner. The Ang II‑induced responses were more marked in the SHR VSMCs, compare with those in the WKY VSMCs, however, the response decreased significantly following ibandronate pretreatment. Treatment with ibandronate significantly decreased the production of ROS, translocation of NADPH oxidase subunit p47phox, and activities of NADPH oxidase and Rac1 in the aorta and VSMCs, and improved the impaired endothelium‑dependent vasodilation in the SHRs. Adding geranylgeraniol, but not farnesol or mevalonate, reversed the inhibitory effects of ibandronate. In addition, inhibiting geranylgeranyl-transferase mimicked the effect of ibandronate on the excess oxidative response. Ibandronate exerted cellular antioxidant effects through the Rac1/NADPH oxidase pathway. These effects may have contributed to the vasoprotective effects on the impaired

  20. Farnesyl pyrophosphate synthase inhibitor, ibandronate, improves endothelial function in spontaneously hypertensive rats

    PubMed Central

    HAN, JIE; JIANG, DONG-MEI; YE, YANG; DU, CHANG-QING; YANG, JIAN; HU, SHEN-JIANG

    2016-01-01

    Reactive oxygen species (ROS), originating predominantly from vascular smooth muscle cells (VSMCs), lead to vascular damage and endothelial dysfunction in rats with hypertension. The downstream signaling pathways of farnesyl pyrophosphate (FPP) synthase, Ras-related C3 botulinum toxin substrate 1 (Rac1) and nicotinamide adenine dinucleotide phosphate (NADPH) oxidase, mediate the generation of ROS. The present study investigated the effect of the FPP synthase inhibitor, ibandronate, on ROS production, the possible beneficial effect on endothelial dysfunction and the underlying mechanisms in spontaneously hypertensive rats (SHRs). The SHRs were treated with ibandronate for 30 days. Endothelium-dependent and independent vasorelaxation were measured in isolated aortic rings. Additionally, VSMCs from the SHRs and Wistar-Kyoto (WKY) rats were cultured. The production of ROS and activation of NADPH oxidase were determined using fluorescence and chemiluminescence, respectively, in vivo and in vitro. Angiotensin II (Ang II) increased ROS production in the cultured VSMCs from the WKY rats and SHRs, in a concentration-dependent manner. The Ang II-induced responses were more marked in the SHR VSMCs, compare with those in the WKY VSMCs, however, the response decreased significantly following ibandronate pretreatment. Treatment with ibandronate significantly decreased the production of ROS, translocation of NADPH oxidase subunit p47phox, and activities of NADPH oxidase and Rac1 in the aorta and VSMCs, and improved the impaired endothelium-dependent vasodilation in the SHRs. Adding geranylgeraniol, but not farnesol or mevalonate, reversed the inhibitory effects of ibandronate. In addition, inhibiting geranylgeranyl-transferase mimicked the effect of ibandronate on the excess oxidative response. Ibandronate exerted cellular antioxidant effects through the Rac1/NADPH oxidase pathway. These effects may have contributed to the vasoprotective effects on the impaired endothelium in

  1. Effects of music composed by Mozart and Ligeti on blood pressure and heart rate circadian rhythms in normotensive and hypertensive rats.

    PubMed

    Lemmer, Björn

    2008-11-01

    There is continuing discussion on the effect of music ("Mozart effect") on numerous functions in man and experimental animals. Radiotelemetry now allows one to monitor cardiovascular functions in freely-moving unrestrained experimental animals. Radiotelemetry was used to monitor systolic and diastolic blood pressure (SBP, DBP), heart rate (HR), and motor activity (MA) in male normotensive WKY and hypertensive SHR animals. Rats were synchronized to a 12 h light (L): 12 h dark (D) regimen in an isolated, ventilated, light-controlled, sound-isolated animal container. Music (Mozart, Symphony # 40; Ligeti, String Quartet # 2) were played for 2 h at 75 dB in the animal cabin starting at the onset of L or D in a cross-over design. Data were collected every 5 min for 24 h under control conditions and during and after music. In addition, plasma concentrations of norepinephrine (NE) were determined in unrestrained animals at 3 h intervals over 24 h. In both WKY and SHR, highly significant circadian rhythms were obtained in SBP, DBP, HR, and MA under control conditions; HR was lower and BP higher in SHR than in WKY. NE was circadian rhythmic in both strains with higher values in D; the increase in NE with immobilization was much more pronounced in SHR than in WKY. The music of Mozart had no effect on either parameter in WKY, neither in L nor in D. In contrast, in SHR, the music of Mozart presented in L significantly decreased HR and left BP unaffected, leading to a small decrease in cardiac output. The music of Ligeti significantly increased BP both in L and in D and reflexively reduced HR in L, the effects being long-lasting over 24 h. Interestingly, white noise at 75 dB had no effect at all on either function in both strains. The effects of both Mozart and Ligeti cannot be attributed to a stress reaction, as stress due to cage switch increased HR and BP both in WKY and SHR. The study clearly demonstrates that music of different character (tempo, rhythm, pitch, tonality) can

  2. Altered vitamin D metabolism in the kidney of the spontaneously hypertensive rat.

    PubMed Central

    Kawashima, H

    1986-01-01

    A decrease in plasma Ca2+ and increases in plasma immunoreactive parathyroid hormone (PTH) have been reported in spontaneously hypertensive (SH) rats as compared with normotensive Wistar-Kyoto (WKy) rats. These changes should lead to a higher plasma 1,25(OH)2D (1,25-dihydroxycholecalciferol/1,25-dihydroxyergocalciferol) concentration in SH rat if the kidney responds appropriately. Plasma 1,25(OH)2D, however, has been reported to be normal in SH rats, suggesting possible impairments of vitamin D metabolism in this animal model of hypertension. To test this possibility, we studied the effect of PTH on renal production of 1,25(OH)2D in SH rats before (4 weeks of age) and after (12 weeks of age) the onset of hypertension. Basal serum levels of 1,25(OH)2D were normal in SH rats at both ages. At 4 weeks of age, the rise in serum 1,25(OH)2D after PTH injection (50 units subcutaneously every 2 h; four times) was also normal in SH rats. By contrast, at 12 weeks of age, the rise in serum 1,25(OH)2D was approximately one-half of that in WKy rats, despite the similar rises in serum Ca2+ levels in both groups by PTH injection. The attenuated rise in serum 1,25(OH)2D in SH rats was consistent with the impaired response of renal 1-hydroxylase (25-hydroxycholecalciferol 1 alpha-hydroxylase) activity to PTH. Basal 1,25(OH)2D production by the kidney in SH rat was higher than that in WKy rats both at 4 and 12 weeks of age. These data suggest that, in SH rats: serum 1,25(OH)2D is inappropriately low in relation to the elevated PTH and this may be due, at least in part, to the impaired responsiveness to PTH of renal 1-hydroxylase and to the enhanced metabolism of 1,25(OH)2D, and elevated PTH or other agents may stimulate the 1-hydroxylase in the kidney even before the onset of hypertension. PMID:3800924

  3. Effect of cocaine on striatal dopamine clearance in a rat model of developmental stress and attention-deficit/hyperactivity disorder.

    PubMed

    Womersley, Jacqueline S; Kellaway, Lauriston A; Stein, Dan J; Gerhardt, Greg A; Russell, Vivienne A

    2016-01-01

    Attention-deficit/hyperactivity disorder (ADHD) and developmental stress are considered risk factors for the development of drug abuse. Though the physiological mechanisms underlying this risk are not yet clear, ADHD, developmental stress and drug abuse are known to share underlying disturbances in dopaminergic neurotransmission. Thus, we hypothesized that clearance of cocaine-induced elevations in striatal dopamine would be prolonged in a rat model of ADHD and that this would be further increased by exposure to developmental stress. In the current study, male spontaneously hypertensive rats (SHRs), a well-validated model of ADHD, and control Wistar-Kyoto (WKY) rats were exposed to either standard rearing (nMS) or a maternal separation (MS) paradigm involving removal of the pups from the dam for 180 min/day over 13 days. This produced a 2 × 2 factorial design (SHR/WKY × nMS/MS) with 5-6 rats/group. Striatal clearance of exogenously applied dopamine was measured via in vivo chronoamperometry, and the difference in dopamine uptake parameters before and after cocaine administration was compared between experimental groups. Cocaine, a potent dopamine transporter inhibitor, reliably increased the clearance time of dopamine though no difference in this parameter was found between SHR and WKY strains. However, developmental stress elevated the cocaine-induced increase in time to clear 50% of exogenously applied dopamine (T50) in SHR but had no effect in WKY rats. These findings suggest that a strain × environment interaction prolongs elevated levels of dopamine thereby potentially increasing the rewarding properties of this drug in SHR. PMID:26394534

  4. Characterizing operant hyperactivity in the Spontaneously Hypertensive Rat

    PubMed Central

    2012-01-01

    Background Operant hyperactivity, the emission of reinforced responses at an inordinately high rate, has been reported in children with ADHD and in the Spontaneously Hypertensive Rat (SHR), the most widely studied animal model of ADHD. The SHR emits behavior at hyperactive levels, relative to a normoactive strain, only when such behavior is seldom reinforced. Because of its dependence on rate of reinforcement, operant hyperactivity appears to be driven primarily by incentive motivation, not motoric capacity. This claim was evaluated in the present study using a novel strategy, based on the organization of behavior in bouts of reinforced responses separated by pauses. Method Male SHR, Wistar-Kyoto (WKY) and Wistar rats (WIS) were exposed each to a multiple variable-interval schedule of sucrose reinforcement (12, 24, 48, 96, and 192 s) between post-natal days (PND) 48 and 93. Responding in each schedule was examined in two epochs, PND 58-62 and 89-93. Parameters of response-reinforcement functions (Herrnstein's hyperbola) and bout-organized behavior were estimated in each epoch. Results SHR emitted higher response rates than WKY and WIS, but only when rate of reinforcement was low (fewer than 2 reinforcers per minute), and particularly in the second epoch. Estimates of Herrnstein's hyperbola parameters suggested the primacy of motivational over motoric factors driving the response-rate differential. Across epochs and schedules, a more detailed analysis of response bouts by SHR revealed that these were shorter than those by WKY, but more frequent than those by WKY and WIS. Differences in bout length subsided between epochs, but differences in bout-initiation rate were exacerbated. These results were interpreted in light of robust evidence linking changes in bout-organization parameters and experimental manipulations of motivation and response-reinforcement contingency. Conclusions Operant hyperactivity in SHR was confirmed. Although incentive motivation appears to

  5. Aspirin-induced AMP-activated protein kinase activation regulates the proliferation of vascular smooth muscle cells from spontaneously hypertensive rats

    SciTech Connect

    Sung, Jin Young; Choi, Hyoung Chul

    2011-05-06

    Highlights: {yields} Aspirin-induced AMPK phosphorylation was greater in VSMC from SHR than WKY. {yields} Aspirin-induced AMPK phosphorylation inhibited proliferation of VSMC from SHR. {yields} Low basal AMPK phosphorylation in SHR elicits increased VSMC proliferation. {yields} Inhibition of AMPK restored decreased VSMC proliferation by aspirin in SHR. {yields} Aspirin exerts anti-proliferative effect through AMPK activation in VSMC from SHR. -- Abstract: Acetylsalicylic acid (aspirin), used to reduce risk of cardiovascular disease, plays an important role in the regulation of cellular proliferation. However, mechanisms responsible for aspirin-induced growth inhibition are not fully understood. Here, we investigated whether aspirin may exert therapeutic effects via AMP-activated protein kinase (AMPK) activation in vascular smooth muscle cells (VSMC) from wistar kyoto rats (WKY) and spontaneously hypertensive rats (SHR). Aspirin increased AMPK and acetyl-CoA carboxylase phosphorylation in a time- and dose-dependent manner in VSMCs from WKY and SHR, but with greater efficacy in SHR. In SHR, a low basal phosphorylation status of AMPK resulted in increased VSMC proliferation and aspirin-induced AMPK phosphorylation inhibited proliferation of VSMCs. Compound C, an AMPK inhibitor, and AMPK siRNA reduced the aspirin-mediated inhibition of VSMC proliferation, this effect was more pronounced in SHR than in WKY. In VSMCs from SHR, aspirin increased p53 and p21 expression and inhibited the expression of cell cycle associated proteins, such as p-Rb, cyclin D, and cyclin E. These results indicate that in SHR VSMCs aspirin exerts anti-proliferative effects through the induction of AMPK phosphorylation.

  6. Comparative cardiopulmonary toxicity of exhausts from soy-based biofuels and diesel in healthy and hypertensive rats

    PubMed Central

    Bass, Virginia L.; Schladweiler, Mette C.; Nyska, Abraham; Thomas, Ronald F.; Miller, Desinia B.; Krantz, Todd; King, Charly; Gilmour, M. Ian; Ledbetter, Allen D.; Richards, Judy E.; Kodavanti, Urmila P.

    2016-01-01

    Increased use of renewable energy sources raise concerns about health effects of new emissions. We analyzed relative cardiopulmonary health effects of exhausts from (1) 100% soy biofuel (B100), (2) 20% soy biofuel + 80% low sulfur petroleum diesel (B20), and (3) 100% petroleum diesel (B0) in rats. Normotensive Wistar–Kyoto (WKY) and spontaneously hypertensive rats were exposed to these three exhausts at 0, 50, 150 and 500 μg/m3, 4 h/day for 2 days or 4 weeks (5 days/week). In addition, WKY rats were exposed for 1 day and responses were analyzed 0 h, 1 day or 4 days later for time-course assessment. Hematological parameters, in vitro platelet aggregation, bronchoalveolar lavage fluid (BALF) markers of pulmonary injury and inflammation, ex vivo aortic ring constriction, heart and aorta mRNA markers of vasoconstriction, thrombosis and atherogenesis were analyzed. The presence of pigmented macrophages in the lung alveoli was clearly evident with all three exhausts without apparent pathology. Overall, exposure to all three exhausts produced only modest effects in most endpoints analyzed in both strains. BALF γ-glutamyl transferase (GGT) activity was the most consistent marker and was increased in both strains, primarily with B0 (B0>B100>B20). This increase was associated with only modest increases in BALF neutrophils. Small and very acute increases occurred in aorta mRNA markers of vasoconstriction and thrombosis with B100 but not B0 in WKY rats. Our comparative evaluations show modest cardiovascular and pulmonary effects at low concentrations of all exhausts: B0 causing more pulmonary injury and B100 more acute vascular effects. BALF GGT activity could serve as a sensitive biomarker of inhaled pollutants. PMID:26514782

  7. Increased intrinsic excitability of muscle vasoconstrictor preganglionic neurons may contribute to the elevated sympathetic activity in hypertensive rats

    PubMed Central

    Briant, Linford J. B.; Stalbovskiy, Alexey O.; Nolan, Matthew F.; Champneys, Alan R.

    2014-01-01

    Hypertension is associated with pathologically increased sympathetic drive to the vasculature. This has been attributed to increased excitatory drive to sympathetic preganglionic neurons (SPN) from brainstem cardiovascular control centers. However, there is also evidence supporting increased intrinsic excitability of SPN. To test this hypothesis, we made whole cell recordings of muscle vasoconstrictor-like (MVClike) SPN in the working-heart brainstem preparation of spontaneously hypertensive (SH) and normotensive Wistar-Kyoto (WKY) rats. The MVClike SPN have a higher spontaneous firing frequency in the SH rat (3.85 ± 0.4 vs. 2.44 ± 0.4 Hz in WKY; P = 0.011) with greater respiratory modulation of their activity. The action potentials of SH SPN had smaller, shorter afterhyperpolarizations (AHPs) and showed diminished transient rectification indicating suppression of an A-type potassium conductance (IA). We developed mathematical models of the SPN to establish if changes in their intrinsic properties in SH rats could account for their altered firing. Reduction of the maximal conductance density of IA by 15–30% changed the excitability and output of the model from the WKY to a SH profile, with increased firing frequency, amplified respiratory modulation, and smaller AHPs. This change in output is predominantly a consequence of altered synaptic integration. Consistent with these in silico predictions, we found that intrathecal 4-aminopyridine (4-AP) increased sympathetic nerve activity, elevated perfusion pressure, and augmented Traube-Hering waves. Our findings indicate that IA acts as a powerful filter on incoming synaptic drive to SPN and that its diminution in the SH rat is potentially sufficient to account for the increased sympathetic output underlying hypertension. PMID:25122704

  8. Increased intrinsic excitability of muscle vasoconstrictor preganglionic neurons may contribute to the elevated sympathetic activity in hypertensive rats.

    PubMed

    Briant, Linford J B; Stalbovskiy, Alexey O; Nolan, Matthew F; Champneys, Alan R; Pickering, Anthony E

    2014-12-01

    Hypertension is associated with pathologically increased sympathetic drive to the vasculature. This has been attributed to increased excitatory drive to sympathetic preganglionic neurons (SPN) from brainstem cardiovascular control centers. However, there is also evidence supporting increased intrinsic excitability of SPN. To test this hypothesis, we made whole cell recordings of muscle vasoconstrictor-like (MVClike) SPN in the working-heart brainstem preparation of spontaneously hypertensive (SH) and normotensive Wistar-Kyoto (WKY) rats. The MVClike SPN have a higher spontaneous firing frequency in the SH rat (3.85 ± 0.4 vs. 2.44 ± 0.4 Hz in WKY; P = 0.011) with greater respiratory modulation of their activity. The action potentials of SH SPN had smaller, shorter afterhyperpolarizations (AHPs) and showed diminished transient rectification indicating suppression of an A-type potassium conductance (IA). We developed mathematical models of the SPN to establish if changes in their intrinsic properties in SH rats could account for their altered firing. Reduction of the maximal conductance density of IA by 15-30% changed the excitability and output of the model from the WKY to a SH profile, with increased firing frequency, amplified respiratory modulation, and smaller AHPs. This change in output is predominantly a consequence of altered synaptic integration. Consistent with these in silico predictions, we found that intrathecal 4-aminopyridine (4-AP) increased sympathetic nerve activity, elevated perfusion pressure, and augmented Traube-Hering waves. Our findings indicate that IA acts as a powerful filter on incoming synaptic drive to SPN and that its diminution in the SH rat is potentially sufficient to account for the increased sympathetic output underlying hypertension. PMID:25122704

  9. Improved Trabecular Bone Structure of 20-Month-Old Male Spontaneously Hypertensive Rats

    PubMed Central

    Lee, Tzu-Cheng; Burghardt, Andrew J.; Yao, Wei; Lane, Nancy E.; Majumdar, Sharmila; Gullberg, Grant T.; Seo, Youngho

    2014-01-01

    A few clinical studies have reported that elderly male participants with hypertensive disease frequently have higher BMD than the normotensive participants at several skeletal sites. The detailed mechanism is still unknown; therefore a study of bone structure and density using the hypertensive animal models could be informative. We used micro-computed tomography (μCT) to quantitatively evaluate the tibial and 3rd lumbar vertebral bones in the 20-month-old male spontaneous hypertensive rat (SHR). The BMD, volume fraction, and the microarchitecture changes of the SHR were compared to those of same-age normotensive controls (Wistar-Kyoto rat, WKY). We found that in the very old (20-month) male rats, the trabecular bone fraction and microstructure were higher than those in the same-age normotensive controls. The observation of the association of hypertension with BMD and bone strength in hypertensive rats warrants further investigations of bone mass and strength in elderly males with hypertension. PMID:25106873

  10. Up-regulation of myocardial connexin-43 in spontaneously hypertensive rats fed red palm oil is most likely implicated in its anti-arrhythmic effects.

    PubMed

    Bačová, Barbara; Radošinská, Jana; Viczenczová, Csilla; Knezl, Vladimír; Dosenko, Victor; Beňova, Tamara; Navarová, Jana; Gonçalvesová, Eva; van Rooyen, Jacques; Weismann, Peter; Slezák, Jan; Tribulová, Narcis

    2012-09-01

    The purpose of this study was to test our hypothesis that red palm oil (RPO) intake may affect abnormalities of myocardial connexin-43 (Cx43) and protein kinase Cε (PKCε) signaling, and consequently the propensity of the spontaneously hypertensive rat heart (SHR) heart to arrhythmias. SHR and Wistar-Kyoto (WKY) rats fed a standard rat chow plus red palm oil (200 µL/day) for 5 weeks were compared with untreated rats. Cytosolic but not particulate PKCε expression as well as Cx43-mRNA, total Cx43 proteins, and its phoshorylated forms were increased, and disordered localization of Cx43 was attenuated in the left ventricle of RPO-fed SHR compared with untreated rats. These alterations were associated with suppression of early post-ischemic-reperfusion-related ventricular tachycardia and electrically inducible ventricular fibrillation. However, the treatment dose of RPO caused down-regulation of myocardial Cx43, but did not alter its cell membrane distribution or overall PKCε expression in WKY rats. It was, however, associated with poor arrhythmia protection, suggesting overdosing. Results indicate that SHR benefit from RPO intake, particularly because of its apparent anti-arrhythmic effects. This protection can be, in part, attributed to the preservation of cell-to-cell communication via up-regulation of myocardial Cx43, but not with PKCε activation. PMID:22908996

  11. Hypertensive vascular remodeling was inhibited by Xuezhikang through the regulation of Fibulin-3 and MMPs in spontaneously hypertensive rats

    PubMed Central

    Lin, Zhong-Wei; Wang, Zhuo; Zhu, Gui-Ping; Li, Bo-Wei; Xie, Wen-Lin; Xiang, Ding-Cheng

    2015-01-01

    Fibulin-3, an extracellular glycoprotein, has been suggested as having functions in vessels. In hypertension, extracellular matrix, matrix metalloproteinases (MMPs) and tissue inhibitors of metalloproteinases (TIMPs) play important roles in cardiovascular remodeling. However, the role of Fibulin-3 as an extracellular glycoprotein in hypertensive vascular remodeling remains unclear. Our study was to determine whether Fibulin-3 and TIMPs/MMPs would affect vascular structure during hypertension and the treatment of Xuezhikang. Thirty spontaneously hypertensive rats (SHRs) aged 8 weeks were randomized to three groups: SHRs control group (SHRs group, n=10), group treated with low dose Xuezhikang (XZK-L, 20 mg/kg/d, n=10) and group treated with high dose Xuezhikang (XZK-H, 200 mg/kg/d, n=10), the normal group was comprised of ten Wistar-Kyoto (WKY) rats of the same age. We showed that serum nitric oxide (NO) in control group was significantly lower than WKY group (P<0.05). Concomitantly, serum oxidized low-density lipoprotein (ox-LDL) was higher than WKY group (P<0.05). The treatment of high dose Xuezhikang significantly dicreased ox-LDL, left ventricular mass index (LVMI) and Wall-to-lumen area ratio (W/L) of thoracic aorta (P<0.05), while serum NO was significantly increasing (P<0.05). Moreover, the expressions of Fibulin-3 and MMP-2, 9 at both protein and mRNA levels were significantly higher in thoracic aorta of SHRs group compared to WKY group by immunohistochemistry and western blotting (P<0.05). However, the levels of Fibulin-3 and MMP-2, 9 were significantly decreased in XZK-H group compared to control group (P<0.05). The level of TIMP-3 had no significance difference between SHRs and WKY groups (P>0.05). So the levels of Fibulin-3 and MMP-2, 9 in SHRs could be inhibited by Xuezhikang. Furthermore, a strong correlation in transcript expression was established between Fibulin-3, and MMP-2 (r=0.81, P<0.05) and MMP-9 (r=0.92, P<0.05) through immunohistochemistry. In

  12. Assessment of the cardiac autonomic neuropathy among the known diabetics and age-matched controls using noninvasive cardiovascular reflex tests in a South-Indian population: A case–control study

    PubMed Central

    Sukla, Pradeep; Shrivastava, Saurabh RamBihariLal; Shrivastava, Prateek Saurabh; Rao, Nambaru Lakshmana

    2016-01-01

    Aim: Diabetes mellitus is a chronic condition characterized by hyperglycemia. The objective of the study was to estimate the prevalence of cardiac autonomic neuropathy in a rural area of South India, among the known diabetics after comparing them with the age-matched healthy controls, utilizing noninvasive cardiac autonomic neuropathy reflex tests. Materials and Methods: A case–control study was conducted for 4 months (October 2014 to January 2015) at an Urban Health and Training Center (UHTC) of a Medical College located in Kancheepuram district, Tamil Nadu. The study was conducted among 126 diagnosed Type 2 diabetes patients and in 152 age- and sex-matched healthy controls to ensure comparability between the cases and controls and, thus, reduce variability due to demographic variables. All the study subjects (cases and controls) were selected from the patients attending UHTC during the study duration, provided they satisfied the inclusion and exclusion criteria. Study participants were subjected to undergo noninvasive cardiac autonomic neuropathy reflex tests. The associations were tested using paired t-test for the continuous (mean ± standard deviation) variables. Results: The overall prevalence of cardiac autonomic neuropathy among diabetic patients was found to be as 53.2% (67/126). On further classification, positive (abnormal) results were obtained in 56 (sympathetic – 44.4%) and 51 (parasympathetic – 40.5%) diabetic cases. Overall, heart rate variation during deep breathing was found to be the most sensitive test to detect parasympathetic autonomic neuropathy while the diastolic blood pressure response to sustained handgrip exercise was the most sensitive method to detect sympathetic neuropathy dysfunction. Conclusion: The overall prevalence of cardiac autonomic neuropathy among diabetic patients was found to be as 53.2%. Even though cardiac autonomic neuropathy can be detected by various invasive tests, noninvasive tests remain a key tool to detect

  13. Blood pressure development of the spontaneously hypertensive rat after concurrent manipulations of dietary Ca2+ and Na+. Relation to intestinal Ca2+ fluxes.

    PubMed Central

    McCarron, D A; Lucas, P A; Shneidman, R J; LaCour, B; Drüeke, T

    1985-01-01

    The blood pressure of the spontaneously hypertensive rat (SHR) is influenced by the Ca2+ content of its diet. As the SHR's greater dependence on dietary calcium may reflect a defect in intestinal calcium absorption, we measured in vitro unidirectional Ca2+ flux (J) in the duodenum-jejunum (four segments each) of the SHR (n = 6) and the normotensive Wistar-Kyoto rat (WKY; n = 6) by a modified Ussing apparatus. Because of the known and postulated interactions between Ca2+ and Na+ in both intestinal and vascular tissue, we assessed in vivo the influence of a concurrent manipulation of Na+ intake (three levels: 0.25%, 0.45%, and 1.0%) on the blood pressure development of SHRs (n = 35) and WKYs (n = 35), between 6 and 20 wk of age, exposed to three levels of dietary calcium (0.1, 1.0, and 2%). Net calcium flux (Jnet) (mean +/- SEM) was significantly (P less than 0.01) lower in the SHR (-2.8 +/- 6.3 nmol/cm2 X h) than in the WKY (34.6 +/- 8.8 nmol/cm2 X h). The SHR's decreased Jnet resulted from a significantly (P less than 0.03) lower mucosa-to-serosa flux (Jm-s) in the SHR (41.0 +/- 5.6 nmol/cm2 X h) compared with the Jm-s of the WKY (70.1 +/- 9.1 nmol/cm2 X h). Serosa-to-mucosa flux for calcium did not differ between the SHR (43.8 +/- 6.6 nmol/cm2 X h) and the WKY (35.5 +/- 8.0 nmol/cm2 X h). The SHR's decreased (P less than 0.002) Jm-s was confirmed by additional measurements in SHRs and WKYs. Jm-s was 36.2 +/- 3.7 nmol/cm2 X h in the SHRs (n = 11) and 64.4 +/- 6.7 nmol/cm2 X h in the WKYs (n = 9). The provision of an increased dietary Ca2+ (2% by weight) and increased Na+ (1%) to the SHR prevented the emergence of hypertension (P less than 0.001) (mean +/- SEM systolic blood pressure at 20 wk of age; 135 +/- 5 mmHg for the 2% Ca2+, 1% Na+ SHR vs. 164 +/- 2 mmHg for the control diet SHR). Ca2+ (0.1%) and Na+ (0.25%) restriction accelerated the SHR's hypertension (192 +/- 2 mmHg) (P less than 0.001) and was associated with higher pressures in the WKY (146 +/- 4 mm

  14. Hypotensive effect of S-adenosyl-L-methionine in hypertensive rats is reduced by autonomic ganglia and KATP channel blockers.

    PubMed

    Sikora, Mariusz; Pham, Kinga; Ufnal, Marcin

    2016-07-01

    S-adenosyl-L-methionine (SAM) is an amino acid involved in a number of physiological processes in the nervous system. Some evidence suggests a therapeutic potential of SAM in hypertension. In this study we investigated the effect of intracerebroventricular (ICV) infusions of SAM on arterial blood pressure in rats. Mean arterial blood pressure (MABP) and heart rate (HR) were measured at baseline and during ICV infusion of either SAM or vehicle (aCSF; controls) in conscious, male normotensive Wistar Kyoto rats (WKY) and Spontaneously Hypertensive Rats (SHR). MABP and HR were not affected by the vehicle. WKY rats infused with SAM (10 μM, 100 μM and 1 mM) showed a biphasic hemodynamic response i.e., mild hypotension and bradycardia followed by a significant increase in MABP and HR. On the contrary, SHR infused with SAM showed a dose-dependent hypotensive response. In separate series of experiments, pretreatment with hexamethonium, a ganglionic blocker as well as pretreatment with glibenclamide, a KATP channel blocker reduced the hemodynamic effects of SAM. SAM may affect the nervous control of arterial blood pressure via the autonomic nervous system and KATP channel-dependent mechanisms. PMID:27108137

  15. Autonomic Nervous System Mediates the Hypotensive Effects of Aqueous and Residual Methanolic Extracts of Syzygium polyanthum (Wight) Walp. var. polyanthum Leaves in Anaesthetized Rats.

    PubMed

    Ismail, A; Mohamed, M; Sulaiman, S A; Wan Ahmad, W A N

    2013-01-01

    Syzygium polyanthum (Wight) Walp. var. polyanthum leaves are consumed as a traditional Malay treatment of hypertension. This study investigates hypotensive potential of aqueous (AESP) and residual methanolic (met-AESP) extracts of S. polyanthum leaves and possible involvement of autonomic receptors. AESP and met-AESP (20 to 100 mg/kg) were intravenously administered into anaesthetized Wistar-Kyoto (WKY) and spontaneously hypertensive (SHR) rats. Blood pressure and heart were monitored for 20 min. AESP and met-AESP induced significant dose-dependent hypotension, but only 100 mg/kg AESP caused mild bradycardia (n = 5). AESP-induced hypotension was more potent than that of met-AESP in WKY. AESP has a faster onset time than that of met-AESP in both WKY and SHR. However, met-AESP-induced hypotension was more sustained than that of AESP in SHR. Blockages of autonomic ganglion and α -adrenergic receptors using hexamethonium and phentolamine (n = 5 for each group) partially attenuated AESP-induced hypotension, suggesting involvement of α -adrenergic receptors. Blockages of autonomic ganglion, β -adrenergic, cholinergic receptors, and nitric oxide production using hexamethonium, propranolol, atropine, and N- ω -nitro-l arginine methyl ester (L-NAME) (n = 5 for each group) partially attenuated met-AESP-induced hypotension, suggesting involvement of β -adrenergic and cholinergic receptors via nitric oxide production. PMID:24454508

  16. Autonomic Nervous System Mediates the Hypotensive Effects of Aqueous and Residual Methanolic Extracts of Syzygium polyanthum (Wight) Walp. var. polyanthum Leaves in Anaesthetized Rats

    PubMed Central

    Ismail, A.; Mohamed, M.; Sulaiman, S. A.; Wan Ahmad, W. A. N.

    2013-01-01

    Syzygium polyanthum (Wight) Walp. var. polyanthum leaves are consumed as a traditional Malay treatment of hypertension. This study investigates hypotensive potential of aqueous (AESP) and residual methanolic (met-AESP) extracts of S. polyanthum leaves and possible involvement of autonomic receptors. AESP and met-AESP (20 to 100 mg/kg) were intravenously administered into anaesthetized Wistar-Kyoto (WKY) and spontaneously hypertensive (SHR) rats. Blood pressure and heart were monitored for 20 min. AESP and met-AESP induced significant dose-dependent hypotension, but only 100 mg/kg AESP caused mild bradycardia (n = 5). AESP-induced hypotension was more potent than that of met-AESP in WKY. AESP has a faster onset time than that of met-AESP in both WKY and SHR. However, met-AESP-induced hypotension was more sustained than that of AESP in SHR. Blockages of autonomic ganglion and α-adrenergic receptors using hexamethonium and phentolamine (n = 5 for each group) partially attenuated AESP-induced hypotension, suggesting involvement of α-adrenergic receptors. Blockages of autonomic ganglion, β-adrenergic, cholinergic receptors, and nitric oxide production using hexamethonium, propranolol, atropine, and N-ω-nitro-l arginine methyl ester (L-NAME) (n = 5 for each group) partially attenuated met-AESP-induced hypotension, suggesting involvement of β-adrenergic and cholinergic receptors via nitric oxide production. PMID:24454508

  17. Inter-Strain Differences in Default Mode Network: A Resting State fMRI Study on Spontaneously Hypertensive Rat and Wistar Kyoto Rat

    PubMed Central

    Huang, Sheng-Min; Wu, Yi-Ling; Peng, Shin-Lei; Peng, Hsu-Hsia; Huang, Teng-Yi; Ho, Kung-Chu; Wang, Fu-Nien

    2016-01-01

    Genetic divergences among mammalian strains are presented phenotypically in various aspects of physical appearance such as body shape and facial features. Yet how genetic diversity is expressed in brain function still remains unclear. Functional connectivity has been shown to be a valuable approach in characterizing the relationship between brain functions and behaviors. Alterations in the brain default mode network (DMN) have been found in human neuropsychological disorders. In this study we selected the spontaneously hypertensive rat (SHR) and the Wistar Kyoto rat (WKY), two inbred rat strains with close genetic origins, to investigate variations in the DMN. Our results showed that the major DMN differences are the activities in hippocampal area and caudate putamen region. This may be correlated to the hyperactive behavior of the SHR strain. Advanced animal model studies on variations in the DMN may have potential to shed new light on translational medicine, especially with regard to neuropsychological disorders. PMID:26898170

  18. NF kappa B and Matrix Metalloproteinase induced Receptor Cleavage in the Spontaneously Hypertensive Rat

    PubMed Central

    Wu, Kwan-I Sharon; Schmid-Schönbein, Geert W.

    2011-01-01

    Recent evidence suggests that inflammation in the spontaneously hypertensive rat (SHR) is associated with an uncontrolled matrix metalloproteinase (MMP) activity. We hypothesize that the transcription factor nuclear factor kappa B (NF–κB) is overexpressed in the SHR, enhancing its MMP activity and enzymatic cleavage of the beta-2 adrenergic receptor (β2AR), thereby diminishing catecholamine-mediated arteriolar vasodilation. NF-κB expression level and translocation were compared between Wistar Kyoto rat (WKY) and SHR kidney, heart and brain. The animals were treated with a NF-κB inhibitor, pyrrolidine dithiocarbamate (PDTC), for ten weeks and correlations between NF-κB and MMP activity were determined. Immunohistochemistry showed that NF-κB expression is increased in untreated SHR kidney (~ 14%) and brain hypothalamus (~ 22%) compared to that in WKY (p <0.05), but not in myocardium and cerebral cortex. After PDTC treatment, the SHR systolic blood pressure was reduced close to WKY levels. NF-κB expression level in treated-SHR was also decreased in kidney and hypothalamus compared to non-treated animals (p <0.05). Furthermore, MMP-2 and -9 activities in SHR plasma were significantly reduced (~41%) by PDTC treatment. Additionally, zymographic analyses and in situ zymography showed decreased MMP-2 activity in kidney homogenates and decreased MMP-1,-9 activities in brain. The level of the β2AR extracellular, but not intracellular, domain density was found reduced in kidney showing a receptor cleavage process that can be blocked by PDTC treatment. These results suggest NF-κB is an important transcription factor in the SHR and may be involved in the enhanced MMP activity and consequently receptor cleavage. PMID:21220710

  19. Febuxostat, a novel xanthine oxidoreductase inhibitor, improves hypertension and endothelial dysfunction in spontaneously hypertensive rats.

    PubMed

    Shirakura, Takashi; Nomura, Johji; Matsui, Chieko; Kobayashi, Tsunefumi; Tamura, Mizuho; Masuzaki, Hiroaki

    2016-08-01

    Xanthine oxidase (XO) is an enzyme responsible for the production of uric acid. XO produces considerable amount of oxidative stress throughout the body. To date, however, its pathophysiologic role in hypertension and endothelial dysfunction still remains controversial. To explore the possible involvement of XO-derived oxidative stress in the pathophysiology of vascular dysfunction, by use of a selective XO inhibitor, febuxostat, we investigated the impact of pharmacological inhibition of XO on hypertension and vascular endothelial dysfunction in spontaneously hypertensive rats (SHRs). Sixteen-week-old SHR and normotensive Wistar-Kyoto (WKY) rats were treated with tap water (control) or water containing febuxostat (3 mg/kg/day) for 6 weeks. Systolic blood pressure (SBP) in febuxostat-treated SHR (220 ± 3 mmHg) was significantly (P < 0.05) decreased compared with the control SHR (236 ± 4 mmHg) while SBP in febuxostat-treated WKY was constant. Acetylcholine-induced endothelium-dependent relaxation in aortas from febuxostat-treated SHR was significantly (P < 0.05) improved compared with the control SHR, whereas relaxation in response to sodium nitroprusside was not changed. Vascular XO activity and tissue nitrotyrosine level, a representative indicator of local oxidative stress, were considerably elevated in the control SHR compared with the control WKY, and this increment was abolished by febuxostat. Our results suggest that exaggerated XO activity and resultant increase in oxidative stress in this experimental model contribute to the hypertension and endothelial dysfunction, thereby supporting a notion that pharmacological inhibition of XO is valuable not only for hyperuricemia but also for treating hypertension and related endothelial dysfunction in human clinics. PMID:27198514

  20. Swimming exercise changes hemodynamic responses evoked by blockade of excitatory amino receptors in the rostral ventrolateral medulla in spontaneously hypertensive rats.

    PubMed

    Ogihara, Cristiana A; Schoorlemmer, Gerhardus H M; Lazari, Maria de Fátima M; Giannocco, Gisele; Lopes, Oswaldo U; Colombari, Eduardo; Sato, Monica A

    2014-01-01

    Exercise training reduces sympathetic activity in hypertensive humans and rats. We hypothesized that the swimming exercise would change the neurotransmission in the rostral ventrolateral medulla (RVLM), a key region involved in sympathetic outflow, and hemodynamic control in spontaneously hypertensive rats (SHR) and Wistar-Kyoto (WKY) rats. Bilateral injections of kynurenic acid (KYN) were carried out in the RVLM in sedentary- (S-) or exercised- (E-) SHR and WKY rats submitted to swimming for 6 weeks. Rats were α-chloralose anesthetized and artificially ventilated, with Doppler flow probes around the lower abdominal aorta and superior mesenteric artery. Injections into the RVLM were made before and after i.v. L-NAME (nitric oxide synthase, NOS, inhibitor). Injections of KYN into the RVLM elicited a major vasodilation in the hindlimb more than in the mesenteric artery in E-SHR compared to S-SHR, but similar decrease in arterial pressure was observed in both groups. Injections of KYN into the RVLM after i.v. L-NAME attenuated the hindlimb vasodilation evoked by KYN and increased the mesenteric vasodilation in E-SHR. Swimming exercise can enhance the hindlimb vasodilation mediated by peripheral NO release, reducing the activation of neurons with EAA receptors in the RVLM in SHR. PMID:24696852

  1. Pharmacologically induced release and modulation of /sup 3/H-norepinephrine (NE) from the isolated portal vein of the spontaneously hypertensive rat (SHR)

    SciTech Connect

    Zhang, S.Q.; Westfall, T.C.

    1986-03-05

    The purpose of the present study was to probe the mechanism for the enhancement of the field-stimulation induced release of /sup 3/H-NE from blood vessels of the SHR compared to normotensive rats. The results of two types of experiments are reported here. First, the effect of nicotine as well as tyramine in inducing the release of /sup 3/H-NE from the superfused portal vein was compared to field stimulation. Secondly, the modulatory effect of serotonin (5-HT) and methacholine (M) on the field stimulation induced release of /sup 3/H-NE was examined. In contrast to the enhancement of the field stimulation induced release of /sup 3/H-NE from the portal vein of the SHR compared to WKY, both nicotine and tyramine produced a similar release of NE from blood vessel obtained from both strains. The fractional release of /sup 3/H-NE to 10/sup -4/, 10/sup -3/ and 10/sup -2/M nicotine was 0.21, 0.67 and 45.5 from WKY and 0.14, 0.68 and 42.4 from SHR. The fractional release of /sup 3/H-NE to 10/sup -4/ and 10/sup -3/M tyramine was 6 and 17 from WKY compared to 7.5 and 17.5 from SHR. The inhibition of /sup 3/H-NE release from the portal vein by both 5-HT and M was similar in blood vessels obtained from SHR and WKY. These results are consistent with there being a defect in the exocytotic induced release of NE from noradrenergic neurons at the vascular neuroeffector junction.

  2. Effect of phorbol ester on the release of atrial natriuretic peptide from the hypertrophied rat myocardium.

    PubMed Central

    Kinnunen, P.; Taskinen, T.; Järvinen, M.; Ruskoaho, H.

    1991-01-01

    1. To determine the cellular mechanisms of atrial natriuretic peptide (ANP) release from ventricular cardiomyocytes, the secretory and the cardiac effects of a phorbol ester, 12-O-tetradecanoyl-phorbol-13-acetate (TPA), known to stimulate protein kinase C activity in heart cells, were studied in isolated, perfused heart preparations from 2- and 21-month-old Wistar-Kyoto (WKY) and spontaneously hypertensive (SHR) rats. TPA was added to the perfusion fluid for 30 min at a concentration of 46 nM after removal of atrial tissue. Additionally, atrial and ventricular levels of immunoreactive ANP (IR-ANP) and ANP mRNA, the distribution of ANP within ventricles as well as the relative contribution of atria and ventricles in the release of ANP were studied. 2. Ventricular hypertrophy that gradually developed in hypertensive rats resulted in remarkable augmentation of ANP gene expression, as reflected by elevated levels of immunoreactive ANP and ANP mRNA. The total amount of IR-ANP in the ventricles of the SHR rats increased 41 fold and ANP mRNA levels 12.9 fold from the age of 2 to 21 months. At the age of 21 months, levels of IR-ANP and ANP mRNA in the ventricles of SHR rats were 5.4 fold and 3.7 fold higher, respectively, than in the normotensive WKY rats. Immunohistochemical studies demonstrated ANP granules within the hypertrophic ventricles of the old SHR rats, but not within normal ventricular tissue. 3. In isolated perfused heart preparations, the severely hypertrophied ventricular tissue of SHR rats after atrialectomy secreted more ANP into the perfusate than did the control hearts.(ABSTRACT TRUNCATED AT 250 WORDS) Images Figure 2 PMID:1826618

  3. Female spontaneously diabetic Torii fatty rats develop nonalcoholic steatohepatitis-like hepatic lesions

    PubMed Central

    Ishii, Yukihito; Motohashi, Yu; Muramatsu, Makoto; Katsuda, Yoshiaki; Miyajima, Katsuhiro; Sasase, Tomohiko; Yamada, Takahisa; Matsui, Tohru; Kume, Shinichi; Ohta, Takeshi

    2015-01-01

    AIM: To investigate the histological features of the liver in spontaneously diabetic Torii (SDT) fatty rats compared with age-matched Sprague-Dawley (SD) rats. METHODS: Female SDT Leprfa (SDT fatty) rats and age-matched SD rats were fed ad libitum. Body weight and biochemical parameters, such as serum glucose, triglyceride (TG), total cholesterol (TC), alanine aminotransferase (ALT) and aspartate aminotransferase (AST) levels as well as fatty acid and TG accumulation in the liver were evaluated at 8 wk of age in the non-fasting state and at 8-wk intervals from 8 to 40 wk of age. Histopathological examinations of the liver were performed using hematoxylin and eosin and Sirius Red staining as well as double staining for ED-1 and toluidine blue. The expression of genes involved in TG synthesis, inflammation, and fibrosis was examined in the liver. RESULTS: SDT fatty rats showed significantly increased body weight compared with SD rats. Serum glucose, TG, and TC levels were significantly higher in SDT fatty rats compared with SD rats. The serum AST and ALT levels in SDT fatty rats were significantly elevated at 8 wk of age compared with the levels in SD rats. Hepatic TG content was marked in SDT fatty rats from 8 to 32 wk of age. Histopathologically, severe hepatosteatosis accompanied by inflammation was observed at 8 wk of age, and fibrosis started to occur at 32 wk of age. Furthermore, Sirius Red and ED-1 staining were increased in the liver at 32 wk of age. Hepatic gene expression related to TG synthesis, inflammation and fibrosis tended to increase in SDT fatty rats compared with SD rats, and the gene expression related to TG secretion was decreased in SDT fatty rats compared with SD rats. CONCLUSION: Female SDT fatty rats have the potential to become an important animal model of nonalcoholic steatohepatitis with type 2 diabetes and obesity. PMID:26290633

  4. Pharmacologic analysis of 7-O-ethyl-fangchinoline-induced vasodilation properties in isolated perfused common carotid arteries of Wistar Kyoto rats and spontaneously hypertensive rats.

    PubMed

    Matsuura, M; Zenda, H; Chiba, S

    1991-10-01

    Using the cannula insertion method, we investigated vascular effects of 7-O-ethyl-fangchinoline (TJN-220) derived from tetrandrine in isolated and perfused common carotid arteries of Wistar Kyoto rats (WKY) and spontaneously hypertensive rats (SHR). A single dose of TJN-220 caused a vasodilation in a dose-related manner in arteries preconstricted by phenylephrine. The vasodilation was not inhibited by propranolol, a potent beta-adrenoceptor antagonist. A potent alpha-antagonist bunazosin inhibited the vasoconstriction to norepinephrine while TJN-220 did not modify the norepinephrine-induced constriction, indicating TJN-220 had no alpha-blocking activity. A potent calcium entry blocker, diltiazem, markedly attenuated the KCl-induced vasoconstriction, and TJN-220 slightly but significantly attenuated the KCl-induced one in large doses. The vasodilation of TJN-220 was not abolished after removing the endothelium by an intraluminal administration of saponin, although the ACh-induced dilation was completely abolished by it. A comparison of vascular responses in WKY and SHR revealed no significant differences. From these results, it is concluded that 1) a new tetrandrine derivative, TJN-220 has relatively long-lasting vasorelaxant properties, 2) the dilatory effects might not be related to adrenergic, muscarinic or endothelium-dependent mechanisms, and 3) the effects might partially be due to calcium entry antagonistic properties. PMID:1806292

  5. Genetic predisposition and early life experience interact to determine glutamate transporter (GLT1) and solute carrier family 12 member 5 (KCC2) levels in rat hippocampus.

    PubMed

    Sterley, Toni-Lee; Howells, Fleur M; Dimatelis, Jacqueline J; Russell, Vivienne A

    2016-02-01

    Attention-deficit/hyperactivity disorder (ADHD) is one of the most common child psychiatric disorders. While it is typically treated with medications that target dopamine and norepinephrine transmission, there is increasing evidence that other neurotransmitter systems, such as glutamate and GABA, may be involved. The aetiology of ADHD is unknown; however, there is evidence that early life stress may contribute to the development of the disorder. In the present study we used proteomic analysis (iTRAQ) followed by sodium dodecyl sulfate polyacrylamide gel electrophoresis and Western blot analysis to investigate hippocampal protein profiles of three rat strains: an animal model of ADHD, spontaneously hypertensive rats (SHR), their control Wistar-Kyoto rats (WKY), and Sprague-Dawley rats (SD). We additionally investigated how these protein profiles are affected by maternal separation, a model of early life stress. Our findings show that solute carrier family 12 member 5 (KCC2) is increased in SHR hippocampus. The glutamate transporter GLT1 splice variant, GLT1b, was increased (proteomic analysis) while total GLT1 (comprised mostly of GLT1a splice variant) was reduced (Western blot analysis) in SHR hippocampus, compared to WKY and SD--a pattern that is consistent with elevated extracellular glutamate levels. Maternal separation increased total GLT1 in hippocampi of SHR, WKY, and SD, and reduced GLT1b in SHR hippocampus. Together these findings provide evidence for disturbed glutamatergic and GABAergic transmission in SHR hippocampus, maternal separation effects on glutamate uptake in hippocampi of all three strains, as well a unique effect of maternal separation on GLT1b levels in SHR hippocampus. These data suggest significant involvement of glutamatergic and GABAergic transmission in the neuropathophysiology of ADHD, and implicates changes in glutamatergic transmission as a result of early life stress. PMID:26464063

  6. Cross-fostering differentially affects ADHD-related behaviors in spontaneously hypertensive rats.

    PubMed

    Gauthier, Angela C; DeAngeli, Nicole E; Bucci, David J

    2015-03-01

    Although both genetic and non-genetic factors are known to contribute to the occurrence of Attention-Deficit Hyperactivity/Disorder (ADHD), little is known about how they impact specific symptoms. We used a cross-fostering approach with an established animal model of ADHD, the Spontaneously Hypertensive Rat strain (SHR), to test the influence of genotype and maternal behavior on ADHD-related behaviors. SHRs and their normo-active genetic relative, Wistar Kyoto rats (WKY), were cross-fostered to an unfamiliar dam of either the same or different strain. Behavioral testing took place when the rats reached adulthood. Locomotor hyperactivity was completely dependent on the strain of the offspring. In contrast, social behavior was primarily determined by the strain of the mother, while attentional orienting behavior was influenced by both the strain of the offspring and the strain of the dam. Anxiety-related behavior was influenced by an interaction between offspring and dam strain. PMID:25647439

  7. Cross-Fostering Differentially Affects ADHD-Related Behaviors in Spontaneously Hypertensive Rats

    PubMed Central

    Gauthier, Angela C.; DeAngeli, Nicole E.; Bucci, David J.

    2014-01-01

    Although both genetic and non-genetic factors are known to contribute to the occurrence of Attention-Deficit Hyperactivity/Disorder (ADHD), little is known about how they impact specific symptoms. We used a cross-fostering approach with an established animal model of ADHD, the Spontaneously Hypertensive Rat strain (SHR), to test the influence of genotype and maternal behavior on ADHD-related behaviors. SHRs and their normo-active genetic relative, Wistar Kyoto rats (WKY), were cross-fostered to an unfamiliar dam of either the same or different strain. Behavioral testing took place when the rats reached adulthood. Locomotor hyperactivity was completely dependent on the strain of the offspring. In contrast, social behavior was primarily determined by the strain of the mother, while attentional orienting behavior was influenced by both the strain of the offspring and the strain of the dam. Anxiety-related behavior was influenced by an interaction between offspring and dam strain. PMID:25647439

  8. Hypotensive and Angiotensin-Converting Enzyme Inhibitory Activities of Eisenia fetida Extract in Spontaneously Hypertensive Rats

    PubMed Central

    Mao, Shumei; Li, Chengde

    2015-01-01

    Objectives. This study aimed to investigate the antihypertensive effects of an Eisenia fetida extract (EFE) and its possible mechanisms in spontaneously hypertensive rats (SHR rats). Methods. Sixteen-week-old SHR rats and Wistar-Kyoto rats (WKY rats) were used in this study. Rats were, respectively, given EFE (EFE group), captopril (captopril group), or phosphate-buffered saline (PBS) (normal control group and SHR group) for 4 weeks. ACE inhibitory activity of EFE in vitro was determined. The systolic blood pressure (SBP) and diastolic blood pressure (DBP) were measured using a Rat Tail-Cuff Blood Pressure System. Levels of angiotensin II (Ang II), aldosterone (Ald), and 6-keto-prostaglandin F1 alpha (6-keto-PGF1α) in plasma were determined by radioimmunoassay, and serum nitric oxide (NO) concentration was measured by Griess reagent systems. Results. EFE had marked ACE inhibitory activity in vitro (IC50 = 2.5 mg/mL). After the 4-week drug management, SHR rats in EFE group and in captopril group had lower SBP and DBP, lower levels of Ang II and Ald, and higher levels of 6-keto-PGF1α and NO than the SHR rats in SHR group. Conclusion. These results indicate that EFE has hypotensive effects in SHR rats and its effects might be associated with its ACE inhibitory activity. PMID:26798397

  9. Age-dependent increase of etheno-DNA-adducts in liver and brain of ROS overproducing OXYS rats

    SciTech Connect

    Nair, Jagadeesan; Sinitsina, Olga; Vasunina, Elena A.; Nevinsky, Georgy A.; Laval, Jacques; Bartsch, Helmut . E-mail: h.bartsch@dkfz.de

    2005-10-21

    Reactive oxygen species (ROS) and lipid peroxidation (LPO) play a role in aging and degenerative diseases. To correlate oxidative stress and LPO-derived DNA damage, we determined etheno-DNA-adducts in liver and brain from ROS overproducing OXYS rats in comparison with age-matched Wistar rats. Liver DNA samples from 3- and 15-month-old OXYS and Wistar rats were analyzed for 1,N {sup 6}-ethenodeoxyadenosine ({epsilon}dA) and 3,N {sup 4}-ethenodeoxycytidine ({epsilon}dC) by immunoaffinity/{sup 32}P-postlabelling. While {epsilon}dA and {epsilon}dC levels were not different in young rats, adduct levels were significantly higher in old OXYS rats when compared to old Wistar or young OXYS rats. Frozen rat brain sections were analyzed for {epsilon}dA by immunostaining of nuclei. Brains from old OXYS rats accumulated {epsilon}dA more frequently than age-matched Wistar rats. Our results demonstrate increased LPO-induced DNA damage in organs of OXYS rats which correlates with their known shorter life-span and elevated frequency of chronic degenerative diseases.

  10. Antihypertensive effects of oleuropein-enriched olive leaf extract in spontaneously hypertensive rats.

    PubMed

    Romero, M; Toral, M; Gómez-Guzmán, M; Jiménez, R; Galindo, P; Sánchez, M; Olivares, M; Gálvez, J; Duarte, J

    2016-01-01

    The effects of chronic consumption of oleuropein-enriched (15% w/w) olive leaf extract (OLE) on blood pressure, endothelial function, and vascular oxidative and inflammatory status in spontaneously hypertensive rats (SHR) were evaluated. Ten Wistar Kyoto rats (WKY) and twenty SHR were randomly assigned to three groups: a control WKY group, a control SHR group and a SHR group treated with OLE (30 mg kg(-1)) for 5 weeks. Long-term administration of OLE reduced systolic blood pressure, heart rate, and cardiac and renal hypertrophy. OLE treatment reversed the impaired aortic endothelium-dependent relaxation to acetylcholine observed in SHR. OLE restored aortic eNOS phosphorylation at Ser-1177 and Thr-495 and increased eNOS activity. OLE eliminated the increased aortic superoxide levels, and reduced the elevated NADPH oxidase activity, as a result of reduced NOX-1 and NOX-2 mRNA levels in SHR. OLE reduced the enhanced vascular TLR4 expression by inhibition of mitogen-activated protein kinase (MAPK) signaling with the subsequent reduction of proinflammatory cytokines. In conclusion, OLE exerts antihypertensive effects on genetic hypertension related to the improvement of vascular function as a result of reduced pro-oxidative and pro-inflammatory status. PMID:26593388

  11. Honey Supplementation in Spontaneously Hypertensive Rats Elicits Antihypertensive Effect via Amelioration of Renal Oxidative Stress

    PubMed Central

    Erejuwa, Omotayo O.; Sulaiman, Siti A.; Ab Wahab, Mohd S.; Sirajudeen, Kuttulebbai N. S.; Salleh, Salzihan; Gurtu, Sunil

    2012-01-01

    Oxidative stress is implicated in the pathogenesis and/or maintenance of elevated blood pressure in hypertension. This study investigated the effect of honey on elevated systolic blood pressure (SBP) in spontaneously hypertensive rats (SHR). It also evaluated the effect of honey on the amelioration of oxidative stress in the kidney of SHR as a possible mechanism of its antihypertensive effect. SHR and Wistar Kyoto (WKY) rats were randomly divided into 2 groups and administered distilled water or honey by oral gavage once daily for 12 weeks. The control SHR had significantly higher SBP and renal malondialdehyde (MDA) levels than did control WKY. The mRNA expression levels of nuclear factor erythroid 2-related factor 2 (Nrf2) and glutathione S-transferase (GST) were significantly downregulated while total antioxidant status (TAS) and activities of GST and catalase (CAT) were higher in the kidney of control SHR. Honey supplementation significantly reduced SBP and MDA levels in SHR. Honey significantly reduced the activities of GST and CAT while it moderately but insignificantly upregulated the Nrf2 mRNA expression level in the kidney of SHR. These results indicate that Nrf2 expression is impaired in the kidney of SHR. Honey supplementation considerably reduces elevated SBP via amelioration of oxidative stress in the kidney of SHR. PMID:22315654

  12. Autonomic control of heart rate and blood pressure in spontaneously hypertensive rats during aversive classical conditioning.

    PubMed

    Hatton, D C; Buchholz, R A; Fitzgerald, R D

    1981-12-01

    An examination was made of the heart rate (HR) and blood pressure (BP) responses of 7-9-wk-old spontaneously hypertensive rats (SHR) and genetical control Wistar/Kyoto (WKY) rats during aversive classical conditioning. Subsequent to the development of conditioned responding (CRs), assessments were made of the effects of selective autonomic blockade by methyl atropine (10 mg/kg), phentolamine (2 mg/kg), and propranolol (2 mg/kg). The CR complex in the two strains consisted of pressor BP CRs in conjunction with vagally mediated decelerative HR CRs in the SHR strain and sympathetically mediated accelerative HR CRs in the WKY strain. The decelerative SHR HR CR did not appear to be secondary to baroreceptor reflex activity, although such activity did appear to be involved in the pressor BP and decelerative HR orienting response (OR) and unconditioned response (UR) complex of the SHRs on the initial application of the CS and the US, respectively. Augmented pressor BP ORs, CRs, and URs in the SHRs relative to the WKYs and differential drug effects on BP and HR baselines of the two strains suggested the presence of enhanced sympathetic activity in the SHRs that was not reflected in the SHR decelerative HR CR. Phentolamine unmasked evidence of reflex beta 2-vasodilation deficiency in the SHRs that could have contributed to the enhancement of their BP OR and CR. PMID:7320284

  13. Honey supplementation in spontaneously hypertensive rats elicits antihypertensive effect via amelioration of renal oxidative stress.

    PubMed

    Erejuwa, Omotayo O; Sulaiman, Siti A; Ab Wahab, Mohd S; Sirajudeen, Kuttulebbai N S; Salleh, Salzihan; Gurtu, Sunil

    2012-01-01

    Oxidative stress is implicated in the pathogenesis and/or maintenance of elevated blood pressure in hypertension. This study investigated the effect of honey on elevated systolic blood pressure (SBP) in spontaneously hypertensive rats (SHR). It also evaluated the effect of honey on the amelioration of oxidative stress in the kidney of SHR as a possible mechanism of its antihypertensive effect. SHR and Wistar Kyoto (WKY) rats were randomly divided into 2 groups and administered distilled water or honey by oral gavage once daily for 12 weeks. The control SHR had significantly higher SBP and renal malondialdehyde (MDA) levels than did control WKY. The mRNA expression levels of nuclear factor erythroid 2-related factor 2 (Nrf2) and glutathione S-transferase (GST) were significantly downregulated while total antioxidant status (TAS) and activities of GST and catalase (CAT) were higher in the kidney of control SHR. Honey supplementation significantly reduced SBP and MDA levels in SHR. Honey significantly reduced the activities of GST and CAT while it moderately but insignificantly upregulated the Nrf2 mRNA expression level in the kidney of SHR. These results indicate that Nrf2 expression is impaired in the kidney of SHR. Honey supplementation considerably reduces elevated SBP via amelioration of oxidative stress in the kidney of SHR. PMID:22315654

  14. Nicotine attenuates spatial learning deficits induced in the rat by perinatal lead exposure.

    PubMed

    Zhou, Mingfu; Suszkiw, Janusz B

    2004-02-27

    Maternally lead (Pb)-exposed, juvenile rats exhibit significant deficits in spatial reference memory acquisition and working memory performance in the Morris water maze (MWM). Acute systemic application of nicotine reverses these deficits without affecting behavioral performance of the age-matched, lead-unexposed control animals. These results suggest that nicotinic agonist treatments can ameliorate learning and memory impairments, presumably by compensating for deficient nicotinic function in developmentally lead-exposed animals. PMID:14746932

  15. Hindlimb suspension diminishes femoral cross-sectional growth in the rat

    NASA Technical Reports Server (NTRS)

    van der Meulen, M. C.; Morey-Holton, E. R.; Carter, D. R.

    1995-01-01

    Growth, functional adaptation, and torsional strength were examined in the femora of 39-day-old male Sprague-Dawley rats subjected to hindlimb suspension for 0, 1, 2, 3, or 4 weeks and were compared with measurements for age-matched control animals. Our goal was to understand the effect of reduced loading on the normal age-related changes in femoral properties during growth. The control animals exhibited growth-related increases in all geometric and torsional properties of the femur. The mean body mass and femoral length of the hindlimb-suspended rats were similar to those of the controls throughout the experiment. Over 4 weeks, the femoral cross-sectional and torsional measurements from the hindlimb-suspended rats demonstrated increases in comparison with the basal values (+33% cross-sectional area, +64% polar moment of inertia, +67% ultimate torque, and +181% torsional rigidity), but the age-matched controls showed significantly greater growth-related increases (+71% cross-sectional area, +136% polar moment of inertia, +127% ultimate torque, and +367% torsional rigidity). The differences in femoral structural strength between the hindlimb-suspended animals and the age-matched controls were attributable to differences in altered cross-sectional geometry.

  16. Increased glutamate-stimulated release of dopamine in substantia nigra of a rat model for attention-deficit/hyperactivity disorder--lack of effect of methylphenidate.

    PubMed

    Warton, Fleur L; Howells, Fleur M; Russell, Vivienne A

    2009-12-01

    Attention-deficit/hyperactivity disorder (ADHD) is a behavioural disorder that has been associated with dysfunction of the dopaminergic system. Abnormal dopamine function could be the result of a primary defect in dopamine neurons (neuronal firing, dopamine transporter, synthesis, receptor function) or an indirect result of impaired glutamate and/or noradrenergic regulation of dopamine neurons. There is considerable evidence to suggest that dopamine release is impaired at mesolimbic and nigrostriatal dopaminergic terminals. However, it is not known whether dysregulation occurs at the level of the cell bodies in the ventral tegmental area of the midbrain (VTA) and substantia nigra (SN). An in vitro superfusion technique was used to measure dopamine release in a widely used model of ADHD, the spontaneously hypertensive rat (SHR), and its normotensive Wistar-Kyoto (WKY) control. At approximately 30 days of age, rats were analysed for behavioural differences in the open field in response to acute treatment with methylphenidate (0.5 to 2 mg/kg in condensed milk, oral self-administration). In addition, rats were treated chronically with methylphenidate (2 mg/kg, oral self-administration, twice daily for 14 days from postnatal day 21 to 34) before the VTA and the SN were analysed for glutamate-stimulated and depolarization-evoked release of dopamine in these areas. In support of its use as an animal model for ADHD, SHR were more active in the open field and displayed less anxiety-like behaviour than WKY. Neither strain showed any effect of treatment with methylphenidate. A significant difference was observed in glutamate-stimulated release of dopamine in the SN of SHR and WKY, with SHR releasing more dopamine, consistent with the hypothesis of altered glutamate regulation of dopamine neurons in SHR. PMID:19821016

  17. Inhibition of TNF-α in hypothalamic paraventricular nucleus attenuates hypertension and cardiac hypertrophy by inhibiting neurohormonal excitation in spontaneously hypertensive rats

    SciTech Connect

    Song, Xin-Ai; Jia, Lin-Lin; Cui, Wei; Zhang, Meng; Chen, Wensheng; Yuan, Zu-Yi; Guo, Jing; Li, Hui-Hua; Zhu, Guo-Qing; Liu, Hao; Kang, Yu-Ming

    2014-11-15

    We hypothesized that chronic inhibition of tumor necrosis factor-alpha (TNF-α) in the hypothalamic paraventricular nucleus (PVN) delays the progression of hypertension and attenuates cardiac hypertrophy by up-regulating anti-inflammatory cytokines, reducing pro-inflammatory cytokines (PICs), decreasing nuclear factor-κB (NF-κB) p65 and NAD(P)H oxidase activities, as well as restoring the neurotransmitters balance in the PVN of spontaneously hypertensive rats (SHR). Adult normotensive Wistar–Kyoto (WKY) and SHR rats received bilateral PVN infusion of a TNF-α blocker (pentoxifylline or etanercept) or vehicle for 4 weeks. SHR rats showed higher mean arterial pressure and cardiac hypertrophy compared with WKY rats, as indicated by increased whole heart weight/body weight ratio, whole heart weight/tibia length ratio, left ventricular weight/tibia length ratio, and cardiac atrial natriuretic peptide (ANP) and beta-myosin heavy chain (β-MHC) mRNA expressions. Compared with WKY rats, SHR rats had higher PVN levels of tyrosine hydroxylase, PICs, the chemokine monocyte chemoattractant protein-1 (MCP-1), NF-κB p65 activity, mRNA expressions of NOX-2 and NOX-4, and lower PVN levels of IL-10 and 67-kDa isoform of glutamate decarboxylase (GAD67), and higher plasma norepinephrine. PVN infusion of pentoxifylline or etanercept attenuated all these changes in SHR rats. These findings suggest that SHR rats have an imbalance between excitatory and inhibitory neurotransmitters, as well as an imbalance between pro- and anti-inflammatory cytokines in the PVN; and chronic inhibition of TNF-α in the PVN delays the progression of hypertension by restoring the balances of neurotransmitters and cytokines in the PVN, and attenuating PVN NF-κB p65 activity and oxidative stress, thereby attenuating hypertension-induced sympathetic hyperactivity and cardiac hypertrophy. - Highlights: • Spontaneously hypertensive rats exhibit neurohormonal excitation in the PVN. • PVN inhibition of

  18. In vitro proliferation of aortic smooth muscle cells from spontaneously hypertensive and normotensive rats.

    PubMed

    Pang, S C

    1989-06-01

    The characteristics and proliferation of aortic smooth muscle cells (SMC) from spontaneously hypertensive rats (SHR) and normotensive Wistar-Kyoto (WKY) rats were studied in culture. Smooth muscle cells were isolated from the tunica media of the thoracic aorta by an explant method. Immunofluorescence microscopy showed that 93-95 per cent of cells were positively labelled with antibodies raised against smooth muscle actin, indicating that these were smooth muscle cells. The proliferative activity was compared between aortic smooth muscle cells from hypertensive and normotensive rats in culture by thymidine incorporation and cell number determinations. The results demonstrate that aortic smooth muscle cells from hypertensive rats grew faster than those from normotensive rats in culture. The increased proliferative activity of cultured aortic smooth muscle cells from hypertensive rats was detectable even when they were cultured in a chemically defined serum-free medium. These data have shown that an increased proliferative activity of aortic smooth muscle cells from hypertensive rats can occur in culture conditions without the influence of arterial pressure or other stimuli as in intact animals. The mechanisms underlying the accelerated proliferative activity of aortic smooth muscle cells from genetically hypertensive rats in vitro remain to be determined. PMID:2754547

  19. Oscillatory contractions in tail arteries from genetically hypertensive rats.

    PubMed

    Lamb, F S; Myers, J H; Hamlin, M N; Webb, R C

    1985-01-01

    This study characterizes a cellular mechanism for oscillatory contractions induced by norepinephrine in vascular smooth muscle from spontaneously hypertensive stroke prone rats (SHRSP). Helically cut strips of tail arteries from SHRSP and normotensive Wistar-Kyoto rats (WKY) were mounted in a muscle bath for measurement of isometric force generation. Norepinephrine-induced responses of arteries from SHRSP were characterized by fluctuations in contractile activity, whereas those in arteries from WKY remained constant with time. The magnitude of the oscillatory contractile activity (frequency X mean amplitude) varied directly with norepinephrine concentration (5.9 X 10(-9) to 1.8 X 10(-7) M). The oscillatory contractile activity varied inversely with the potassium concentration (3-20 mM) of the buffer solution and directly with the calcium concentration (0.1-5.0 mM) of the buffer solution. The oscillatory activity was converted to maintained contraction by barium (10(-4) M), quinidine (3 X 10(-6) M), sparteine (10(-3) M), D-600 (10(-7) M), and nifedipine (10(-8) M). Tetraethylammonium and 3,4-diaminopyridine, inhibitors of voltage-dependent potassium channels, did not alter the oscillatory contractile activity induced by norepinephrine. These observations suggest that oscillatory contractile activity in tail arteries from SHRSP is caused by an abnormal variation in potassium efflux during stimulation with norepinephrine. The altered potassium efflux appears to be related to calcium entry, which is sensitive to inhibition by channel blockers. This altered membrane property may contribute to changes in vascular sensitivity in hypertension. PMID:3997233

  20. Resistance Training in Spontaneously Hypertensive Rats with Severe Hypertension

    PubMed Central

    Neves, Rodrigo Vanerson Passos; Souza, Michel Kendy; Passos, Clévia Santos; Bacurau, Reury Frank Pereira; Simoes, Herbert Gustavo; Prestes, Jonato; Boim, Mirian Aparecida; Câmara, Niels Olsen Saraiva; Franco, Maria do Carmo Pinho; Moraes, Milton Rocha

    2016-01-01

    Background Resistance training (RT) has been recommended as a non-pharmacological treatment for moderate hypertension. In spite of the important role of exercise intensity on training prescription, there is still no data regarding the effects of RT intensity on severe hypertension (SH). Objective This study examined the effects of two RT protocols (vertical ladder climbing), performed at different overloads of maximal weight carried (MWC), on blood pressure (BP) and muscle strength of spontaneously hypertensive rats (SHR) with SH. Methods Fifteen male SHR [206 ± 10 mmHg of systolic BP (SBP)] and five Wistar Kyoto rats (WKY; 119 ± 10 mmHg of SBP) were divided into 4 groups: sedentary (SED-WKY) and SHR (SED-SHR); RT1-SHR training relative to body weight (~40% of MWC); and RT2-SHR training relative to MWC test (~70% of MWC). Systolic BP and heart rate (HR) were measured weekly using the tail-cuff method. The progression of muscle strength was determined once every fifteen days. The RT consisted of 3 weekly sessions on non-consecutive days for 12-weeks. Results Both RT protocols prevented the increase in SBP (delta - 5 and -7 mmHg, respectively; p > 0.05), whereas SBP of the SED-SHR group increased by 19 mmHg (p < 0.05). There was a decrease in HR only for the RT1 group (p < 0.05). There was a higher increase in strength in the RT2 (140%; p < 0.05) group as compared with RT1 (11%; p > 0.05). Conclusions Our data indicated that both RT protocols were effective in preventing chronic elevation of SBP in SH. Additionally, a higher RT overload induced a greater increase in muscle strength. PMID:26840054

  1. Natriuretic peptide resistance of mesenteric arteries in spontaneous hypertensive rat is alleviated by exercise.

    PubMed

    Yu, J; Zhang, B; Su, X-L; Tie, R; Chang, P; Zhang, X-C; Wang, J-B; Zhao, G; Zhu, M-Z; Zhang, H-F; Chen, B-Y

    2016-06-20

    Proximal resistance vessels, such as the mesenteric arteries, contribute substantially to the peripheral resistance. The reactivity of resistance vessels to vasoactive substance like natriuretic peptides plays an important role in the regulation of blood pressure. In current study, we investigated the reactivity of mesenteric arteries to atrial natriuretic peptide (ANP), a well known vasodilating factor, in spontaneously hypertensive rats (SHR), as well as the effects of exercise training on it. As a result, ANP-induced vasorelaxation was attenuated in SHR with significantly increased phosphodiesterase type 5 (PDE5), and decreased cGMP/ANP ratio, compared with WKY rats as control. Intriguingly, the decreased reactivity to ANP in SHR was markedly reversed by exercise training. In addition, ANP resistance of in vitro mesenteric arteries was diminished by sildenafil a potent selective inhibitor of PDE5. In conclusion, ANP resistance occurs in resistance vessels of SHR, suggesting predisposition to hypertension, which can be reversed by exercise. PMID:26447511

  2. Structural and functional adaptation in the rat myocardium and coronary vascular bed caused by changes in pressure and volume load.

    PubMed

    Friberg, P

    1985-01-01

    The structural and functional characteristics of the myocardium and coronary vessels are major determinants of cardiac function. Both can be influenced by long-term hemodynamic changes, such as sustained alterations of pressure and/or volume load on the heart. The diastolic pressure-volume relationship of the left ventricle (LV) was evaluated in arrested isolated hearts from spontaneously hypertensive rats (SHR), Wistar Kyoto normotensive rats (WKY), pregnant and hyperthyroid SHR and WKY. Such measurements of the LV dimensions were also performed after antihypertensive therapy by hydralazine, felodipine, metoprolol and alpha-methyldopa. Cardiac function was studied in a perfusion system in which external work could be measured at various pre- and afterloads. Coronary flow and O2-extraction could also be determined. LV function was examined in young and aged SHR and WKY, in metoprolol-felodipine treated SHR and in two-kidney, one clip hypertension before and after its reversal by renal artery unclipping. The SHR LV in early established primary hypertension mainly showed eccentric hypertrophy, with increased LV enddiastolic volume for a given filling pressure and a marginal reduction of wall to lumen ratio (w/ri). Hence, a higher stroke volume could be delivered for a given myocardial fibre shortening. Nevertheless, when challenged by high afterloads, LV function in SHR was considerably augmented compared with WKY. The antihypertensive drugs used reduce arterial pressure in different ways, which may differently affect cardiac design. Generally, the results suggest that wall thickness was structurally adapted to keep w/ri balanced to the prevailing blood pressure, while internal radius was adapted to long-term changes in diastolic filling. Thus sympatholytic drugs which lowered arterial pressure by reducing cardiac output, induced a reduction of wall thickness at a minor change of internal radius, while drugs which reduced pressure by systemic vasodilation increased

  3. Age- and hypertension-induced changes in abnormal contractions in rat aorta.

    PubMed

    Abeywardena, Mahinda Y; Jablonskis, Lina T; Head, Richard J

    2002-12-01

    The current investigation explored the potential age-dependant modulation of abnormal spontaneous constrictions (thromboxane-like) in the spontaneously hypertensive rat (SHR) aorta, observed only after the inhibition of endogenous production of nitric oxide (NO). Aortic rings from SHR and Wistar-Kyoto (WKY) control rats of varying ages (4, 8, 12, and 18 months) were mounted in organ baths, and changes in tension were monitored. Inhibition of NO with Nomega-nitro-L-arginine (NOLA) unmasked a slow contraction, which appeared to be age dependent (p < 0.05). This contraction was found in SHRs of all age groups and in older WKY rats. Denuding the endothelium in young SHRs did not influence the constriction, confirming a nonendothelial cell origin, while in the older groups this led to a 30-40% reduction in contraction. Comparable attenuation of the constrictor response was observed after incubation of endothelium intact rings with superoxide dismutase (100 U/ml) or 3-amino-1,2,4-triazole. Of the residual activity that was unaffected by free radical scavengers or de-endothelialization, 60-70% was sensitive to cyclooxygenase inhibition by indomethacin and/or ibuprofen. The thromboxane (TxA ) receptor antagonist SQ29548 induced a complete reversal of the abnormal constriction. In contrast, thromboxane synthetase inhibition had no effect, ruling out any involvement of TxA in mediating this abnormality. Collectively, these observations support the view that as compared with the normotensive setting, contraction induced by NO inhibition in the SHR develops prematurely and deteriorates more rapidly during the aging process. In aged rats, prostaglandin endoperoxide intermediates PGG /H and endothelium-derived free radicals rather than TxA per se appear to contribute to the NOLA-dependent TxA -like vasoconstriction. PMID:12451327

  4. Biliary and renal excretions of cefpiramide in Eisai hyperbilirubinemic rats.

    PubMed Central

    Muraoka, I; Hasegawa, T; Nadai, M; Wang, L; Haghgoo, S; Tagaya, O; Nabeshima, T

    1995-01-01

    Eisai hyperbilirubinemic mutant rats (EHBRs) with conjugated hyperbilirubinemia were recently derived from Sprague-Dawley rats (SDRs). The pharmacokinetic characteristics of the beta-lactam antibiotic cefpiramide (CPM), which is mainly excreted into bile, were investigated in 10- and 20-week-old EHBRs and were compared with those in 20-week-old healthy SDRs. The pharmacokinetic parameters of CPM after an intravenous administration of 20 mg/kg of body weight were estimated for each rat by noncompartmental methods. When compared with age-matched healthy SDRs, significant decreases (by approximately 30%) in the systemic clearance of CPM were observed in 20-week-old EHBRs. The biliary clearance of CPM in 20-week-old EHBRs markedly decreased to less than 10% of that in age-matched healthy SDRs, while total urinary recovery of unchanged CPM increased to threefold and renal clearance doubled. However, no significant differences in any of the pharmacokinetic parameters of CPM were observed between the two groups of EHBRs. There were no significant differences among the three groups in the steady-state volume of distribution of CPM. The present study indicates that hyperbilirubinemia induces an increase in the urinary excretion ability of CPM in return for a reduction in the biliary excretion. PMID:7695332

  5. Detrimental effects of acute nicotine on the response-withholding performance of spontaneously hypertensive and Wistar Kyoto rats

    PubMed Central

    Mazur, Gabriel J.; Wood-Isenberg, Gabriel; Watterson, Elizabeth; Sanabria, Federico

    2014-01-01

    Rationale Attention-Deficit Hyperactivity Disorder (ADHD) is associated with a higher prevalence of smoking, which may be related to potential therapeutic effects of nicotine on ADHD symptoms. Whereas nicotine offers robust improvements in sustained attention, the effects of nicotine on impulsivity are unclear. Objectives The present study examined the effects of nicotine on the response inhibition capacity of spontaneously hypertensive rats (SHR), an animal model of ADHD, compared to that of a normotensive control Wistar Kyoto (WKY) using the Fixed Minimum Interval (FMI) schedule of reinforcement. Methods Tests were conducted following acute injections of subcutaneous nicotine (0.1 – 0.6 mg/kg). On each FMI trial, the first lever press initiated an inter-response time (IRT); a head entry into a food receptacle terminated the IRT. IRTs longer than 6 s were intermittently reinforced with sucrose. Results A model that assumes that only a proportion of IRTs are sensitive to the timing contingencies of the FMI provided a close fit to the data, regardless of strain or treatment. No baseline difference in FMI performance was observed between SHR and WKY. Nicotine reduced the duration of timed IRTs and the duration of latencies to the IRT-initiating lever press similarly for both strains. Nicotine dose-dependently increased the proportion of timed IRTs; the dose-response curve was shifted leftwards in SHR relative to WKY. Conclusions These results suggest that nicotine (a) reduces response-inhibition capacity (b) enhances the reinforcement efficacy of sucrose, and (c) dose-dependently enhances attention-like sensitivity to contingencies of reinforcement, through mechanisms that are yet unknown. PMID:24414609

  6. Differences in the dynamic baroreflex characteristics of unmyelinated and myelinated central pathways are less evident in spontaneously hypertensive rats.

    PubMed

    Turner, Michael J; Kawada, Toru; Shimizu, Shuji; Fukumitsu, Masafumi; Sugimachi, Masaru

    2015-12-01

    The aim of the study was to identify the contribution of myelinated (A-fiber) and unmyelinated (C-fiber) baroreceptor central pathways to the baroreflex control of sympathetic nerve activity (SNA) and arterial pressure (AP) in anesthetized Wistar-Kyoto (WKY; n = 8) and spontaneously hypertensive rats (SHR; n = 8). The left aortic depressor nerve (ADN) was electrically stimulated with two types of binary white noise signals designed to preferentially activate A-fibers (A-BRx protocol) or C-fibers (C-BRx protocol). In WKY, the central arc transfer function from ADN stimulation to SNA estimated by A-BRx showed strong derivative characteristics with the slope of dynamic gain between 0.1 and 1 Hz (Gslope) of 14.63 ± 0.89 dB/decade. In contrast, the central arc transfer function estimated by C-BRx exhibited nonderivative characteristics with Gslope of 0.64 ± 1.13 dB/decade. This indicates that A-fibers are important for rapid baroreflex regulation, whereas C-fibers are likely important for more sustained regulation of SNA and AP. In SHR, the central arc transfer function estimated by A-BRx showed higher Gslope (18.46 ± 0.75 dB/decade, P < 0.01) and that estimated by C-BRx showed higher Gslope (8.62 ± 0.64 dB/decade, P < 0.001) with significantly lower dynamic gain at 0.01 Hz (6.29 ± 0.48 vs. 2.80 ± 0.36%/Hz, P < 0.001) compared with WKY. In conclusion, the dynamic characteristics of the A-fiber central pathway are enhanced in the high-modulation frequency range (0.1-1 Hz) and those of the C-fiber central pathway are attenuated in the low-modulation frequency range (0.01-0.1 Hz) in SHR. PMID:26377561

  7. Prolonged performance of a high repetition low force task induces bone adaptation in young adult rats, but loss in mature rats.

    PubMed

    Massicotte, Vicky S; Frara, Nagat; Harris, Michele Y; Amin, Mamta; Wade, Christine K; Popoff, Steven N; Barbe, Mary F

    2015-12-01

    We have shown that prolonged repetitive reaching and grasping tasks lead to exposure-dependent changes in bone microarchitecture and inflammatory cytokines in young adult rats. Since aging mammals show increased tissue inflammatory cytokines, we sought here to determine if aging, combined with prolonged performance of a repetitive upper extremity task, enhances bone loss. We examined the radius, forearm flexor muscles, and serum from 16 mature (14-18 months of age) and 14 young adult (2.5-6.5 months of age) female rats after performance of a high repetition low force (HRLF) reaching and grasping task for 12 weeks. Young adult HRLF rats showed enhanced radial bone growth (e.g., increased trabecular bone volume, osteoblast numbers, bone formation rate, and mid-diaphyseal periosteal perimeter), compared to age-matched controls. Mature HRLF rats showed several indices of radial bone loss (e.g., decreased trabecular bone volume, and increased cortical bone thinning, porosity, resorptive spaces and woven bone formation), increased osteoclast numbers and inflammatory cytokines, compared to age-matched controls and young adult HRLF rats. Mature rats weighed more yet had lower maximum reflexive grip strength, than young adult rats, although each age group was able to pull at the required reach rate (4 reaches/min) and required submaximal pulling force (30 force-grams) for a food reward. Serum estrogen levels and flexor digitorum muscle size were similar in each age group. Thus, mature rats had increased bone degradative changes than in young adult rats performing the same repetitive task for 12 weeks, with increased inflammatory cytokine responses and osteoclast activity as possible causes. PMID:26517953

  8. Neurobehavioral Abnormalities in the HIV-1 Transgenic Rat Do Not Correspond to Neuronal Hypometabolism on 18F-FDG-PET

    PubMed Central

    Papadakis, Georgios Z.; Muthusamy, Siva; Lee, Dianne E.; Ibrahim, Wael G.; Nair, Anand; Koziol, Deloris; Maric, Dragan; Hammoud, Dima A.

    2016-01-01

    Motor and behavioral abnormalities are common presentations among individuals with HIV-1 associated neurocognitive disorders (HAND). We investigated whether longitudinal motor and behavioral performance in the HIV-1 transgenic rat (Tg), a commonly used neuro-HIV model, corresponded to in vivo neuronal death/dysfunction, by using rotarod and open field testing in parallel to [18F] 2-fluoro-2-deoxy-D-glucose (FDG) positron emission tomography (PET). We demonstrated that age-matched non-Tg wild type (WT) rats outperformed the HIV-1 Tg rats at most time points on rotarod testing. Habituation to rotarod occurred at 8 weeks of age (fifth weekly testing session) in the WT rats but it never occurred in the Tg rats, suggesting deficits in motor learning. Similarly, in open field testing, WT rats outperformed the Tg rats at most time points, suggesting defective exploratory/motor behavior and increased emotionality in the Tg rat. Despite the neurobehavioral abnormalities, there were no concomitant deficits in 18F-FDG uptake in Tg rats on PET compared to age-matched WT rats and no significant longitudinal loss of FDG uptake in either group. The negative PET findings were confirmed using 14C- Deoxy-D-glucose autoradiography in 32 week-old Tg and WT rats. We believe that the neuropathology in the HIV-1 Tg rat is more likely a consequence of neuronal dysfunction rather than overt neurodegeneration/neuronal cell death, similar to what is seen in HIV-positive patients in the post-ART era. PMID:27010205

  9. Neurobehavioral Abnormalities in the HIV-1 Transgenic Rat Do Not Correspond to Neuronal Hypometabolism on 18F-FDG-PET.

    PubMed

    Reid, William C; Casas, Rafael; Papadakis, Georgios Z; Muthusamy, Siva; Lee, Dianne E; Ibrahim, Wael G; Nair, Anand; Koziol, Deloris; Maric, Dragan; Hammoud, Dima A

    2016-01-01

    Motor and behavioral abnormalities are common presentations among individuals with HIV-1 associated neurocognitive disorders (HAND). We investigated whether longitudinal motor and behavioral performance in the HIV-1 transgenic rat (Tg), a commonly used neuro-HIV model, corresponded to in vivo neuronal death/dysfunction, by using rotarod and open field testing in parallel to [18F] 2-fluoro-2-deoxy-D-glucose (FDG) positron emission tomography (PET). We demonstrated that age-matched non-Tg wild type (WT) rats outperformed the HIV-1 Tg rats at most time points on rotarod testing. Habituation to rotarod occurred at 8 weeks of age (fifth weekly testing session) in the WT rats but it never occurred in the Tg rats, suggesting deficits in motor learning. Similarly, in open field testing, WT rats outperformed the Tg rats at most time points, suggesting defective exploratory/motor behavior and increased emotionality in the Tg rat. Despite the neurobehavioral abnormalities, there were no concomitant deficits in 18F-FDG uptake in Tg rats on PET compared to age-matched WT rats and no significant longitudinal loss of FDG uptake in either group. The negative PET findings were confirmed using 14C- Deoxy-D-glucose autoradiography in 32 week-old Tg and WT rats. We believe that the neuropathology in the HIV-1 Tg rat is more likely a consequence of neuronal dysfunction rather than overt neurodegeneration/neuronal cell death, similar to what is seen in HIV-positive patients in the post-ART era. PMID:27010205

  10. Activin A increases arterial pressure in the hypothalamic paraventricular nucleus in rats by angiotension II.

    PubMed

    Ge, Jingyan; Fan, Yuqi; Lu, Yaqiong; Qi, Yan; Wang, Minghua; Liu, Zhonghui

    2016-06-15

    Activin A, a member of the transforming growth factor β superfamily, plays an important role in the central nervous system as a neurotrophic and neuroprotective factor. The hypothalamic paraventricular nucleus (PVN) in the central nervous system is characterized as an important integrative site to regulate arterial pressure (AP). However, whether activin A in the PVN is involved in the regulation of AP is not well characterized. This study aimed to determine the effect of activin A on AP in the PVN in rats. The results showed that activin βA, activin type IIA and IIB receptors (ActRIIA and ActRIIB), and Smad2 and Smad3 mRNA expressions were detectable in the PVN of WKY rats by reverse-transcription PCR, and the expression of ActRIIA protein in the PVN was further confirmed by immunohistochemical staining. A microinjection of angiotensin II (AngII) (0.1 nmol/100 nl) or activin A (2 ng/100 nl) into the PVN increased AP significantly in WKY rats (P<0.05). Moreover, activin A (5 ng/ml) promoted AngII release from the primary cultured PVN neurons that can increase AP and upregulated the expressions of ActRIIA and Smad3 mRNA in the primary cultured PVN neurons (P<0.05). These data suggest that activin A can regulate AP in the PVN in an autocrine or a paracrine manner, which is related to AngII release and the ActRIIA-Smad3 signal pathway. PMID:27138952

  11. Chronic treatment with red wine modulates the purinergic neurotransmission and decreases blood pressure in hypertensive SHR and diabetic-STZ rats.

    PubMed

    Musial, Diego C; Bomfim, Guilherme H S; Miranda-Ferreira, Regiane; Caricati-Neto, Afonso; Jurkiewicz, Aron; Jurkiewicz, Neide H

    2015-01-01

    It is known that red wine has cardioprotective properties. However, its influence is unknown about purinergic system. Therefore, we study the influence of the treatment with red wine or ethanol in purinergic neurotransmission. We used Wistar Kyoto rats (WKY), diabetic streptozotocin-induced WKY and spontaneously hypertensive rats (SHR), treated with red wine (12.5%) or ethanol (12.5%). The cardiovascular function stimulated with purinergic agonists and systolic blood pressure (SBP) was assessed. In atria of diabetics and SHRs, the P1 receptor response was decreased, unlike the P2 receptor response was increased. Likewise, in aorta the affinity to adenosine (ADO) was decreased from SHRs and diabetics. Furthermore, the P2X function was increased just SHRs. All these alterations were improved after treatment with red wine, resulting in reduction of SBP from diabetics and SHRs, but not when treated with ethanol. This study has important implications, because it is shown that consumption of red wine can improve cardiovascular system by purinergic neurotransmission. PMID:26088281

  12. Measuring Regional Changes in the Diastolic Deformation of the Left Ventricle of SHR Rats Using microPET Technology and Hyperelastic Warping

    SciTech Connect

    Gullberg, Grant T; VERESS , ALEXANDER I.; WEISS, JEFFREY A.; HUESMAN, RONALD H.; REUTTER, BRYAN W.; TAYLOR , SCOTT E.; SITEK , AREK; FENG, BING; YANG , YONGFENG; GULLBERG, GRANT T.

    2008-04-04

    The objective of this research was to assess applicability of a technique known as hyperelastic warping for the measurement of local strains in the left ventricle (LV) directly from microPET image data sets. The technique uses differences in image intensities between template (reference) and target (loaded) image data sets to generate a body force that deforms a finite element (FE) representation of the template so that it registers with the target images. For validation, the template image was defined as the end-systolic microPET image data set from a Wistar Kyoto (WKY) rat. The target image was created by mapping the template image using the deformation results obtained from a FE model of diastolic filling. Regression analysis revealed highly significant correlations between the simulated forward FE solution and image derived warping predictions for fiber stretch (R2 = 0.96), circumferential strain (R2 = 0.96), radial strain (R2 = 0.93), and longitudinal strain (R2 = 0.76) (p<0.001for all cases). The technology was applied to microPET image data of two spontaneously hypertensive rats (SHR) and a WKY control. Regional analysis revealed that, the lateral freewall in the SHR subjects showed the greatest deformation compared with the other wall segments. This work indicates that warping can accurately predict the strain distributions during diastole from the analysis of microPET data sets.

  13. Altered dendritic arborization of amygdala neurons in young adult rats orally intubated with Clitorea ternatea aqueous root extract.

    PubMed

    Rai, Kiranmai S; Murthy, K Dilip; Rao, Muddanna S; Karanth, K Sudhakar

    2005-07-01

    Young adult (60 day old) Wistar rats of either sex were orally intubated with 50 mg/kg body weight and 100 mg/kg body weight of aqueous root extract of Clitoria ternatea (CTR) for 30 days, along with age-matched saline controls. These rats were then subjected to passive avoidance tests and the results from these studies showed a significant increase in passive avoidance learning and retention. Subsequent to the passive avoidance tests, these rats were killed by decapitation. The amygdala was processed for Golgi staining and the stained neurons were traced using a camera lucida and analysed. The results showed a significant increase in dendritic intersections, branching points and dendritic processes arising from the soma of amygdaloid neurons in CTR treated rats especially in the 100 mg/kg group of rats, compared with age-matched saline controls. This improved dendritic arborization of amygdaloid neurons correlates with the increased passive avoidance learning and memory in the CTR treated rats as reported earlier. The results suggest that Clitoria ternatea aqueous root extract enhances memory by increasing the functional growth of neurons of the amygdala. PMID:16161034

  14. Sex differences in the blood antioxidant defense system in juvenile rats with various genetic predispositions to hypertension.

    PubMed

    Horvathova, Martina; Zitnanova, Ingrid; Kralovicova, Zuzana; Balis, Peter; Puzserova, Angelika; Muchova, Jana; Kluknavsky, Michal; Durackova, Zdenka; Bernatova, Iveta

    2016-02-01

    This study investigated the contribution of blood oxidative stress (OS) to the development of hypertension, as well as sex differences in the antioxidant defense system (ADS) in genetic models of hypertension. Nine-week-old normotensive Wistar-Kyoto (WKY) rats, borderline hypertensive rats (BHR) and spontaneously hypertensive rats (SHR) of both sexes were used. Systolic blood pressure (SBP) was determined by tail-cuff plethysmography, the trolox equivalent antioxidant capacity (TEAC) and the concentration of lipid peroxides (LP) were determined in plasma. The activity of the antioxidant enzymes Cu/Zn-superoxide dismutase (SOD), glutathione peroxidase (GPx) and catalase (CAT) was determined in erythrocytes. SBP was significantly elevated in BHR and SHR in both sexes. BHR and SHR males had a higher SBP than the respective females. Sex-dependent differences in the ADS were found only in SHR, in which TEAC, SOD and CAT were significantly higher in males than in females. No differences in TEAC, SOD, CAT and GPx were observed between BHR (males and females) and WKY controls. LP levels were similar in all the groups investigated. Significant positive correlations were observed between SBP and both SOD and CAT. TEAC correlated positively with SOD and LP. As no signs of oxidative damage to lipids were found in young BHR and SHR of either sex, OS in the blood does not seem to be causatively related to the development of hypertension in these rats. However, despite activated antioxidant defenses, the positive correlation between plasma TEAC and LP suggests that oxidative damage is progressing slowly and therefore it seems to be a consequence rather than the cause of hypertension. PMID:26510784

  15. Effect of Silodosin, an Alpha1A-Adrenoceptor Antagonist, on Ventral Prostatic Hyperplasia in the Spontaneously Hypertensive Rat

    PubMed Central

    Shimizu, Shogo; Shimizu, Takahiro; Tsounapi, Panagiota; Higashi, Youichirou; Martin, Darryl T.; Nakamura, Kumiko; Honda, Masashi; Inoue, Keiji; Saito, Motoaki

    2015-01-01

    Background A decreased prostatic blood flow could be one of the risk factors for benign prostatic hyperplasia/benign prostatic enlargement. The spontaneously hypertensive rat (SHR) shows a chronic prostatic ischemia and hyperplastic morphological abnormalities in the ventral prostate. The effect of silodosin, a selective alpha1A-adrenoceptor antagonist, was investigated in the SHR prostate as a prostatic hyperplasia model focusing on prostatic blood flow. Methods Twelve-week-old male SHRs were administered perorally with silodosin (100 μg/kg/day) or vehicle once daily for 6 weeks. Wistar Kyoto (WKY) rats were used as normotensive controls and were treated with the vehicle. The effect of silodosin on blood pressure and prostatic blood flow were estimated and then the prostates were removed and weighed. The tissue levels of malondialdehyde (MDA), interleukin-6 (IL-6), chemokine (C-X-C motif) ligand 1/cytokine-induced neutrophil chemoattractant 1 (CXCL1/CINC1), tumor necrosis factor-alpha (TNF-α), transforming growth factor beta 1 (TGF-β1), basic fibroblast growth factor (bFGF) and alpha-smooth muscle actin (α-SMA) were measured. The histological evaluation was also performed by hematoxylin and eosin staining. Results There was a significant increase in blood pressure, prostate weight, prostate body weight ratio (PBR), tissue levels of MDA, IL-6, CXCL1/CINC1, TNF-α, TGF-β1, bFGF and α-SMA in the SHR compared to the WKY rat. The ventral prostate in the SHR showed the morphological abnormalities compared to the WKY rat. Prostatic blood flow was decreased in the SHR. However, treatment with silodosin significantly restored the decreased prostatic blood flow in the SHR. Moreover, silodosin normalized tissue levels of MDA, IL-6, CXCL1/CINC1, TNF-α, TGF-β1, bFGF and α-SMA, and it ameliorated ventral prostatic hyperplasia in the SHR excluding blood pressure. Silodosin decreased PBR but not prostate weight in the SHR. Conclusions Silodosin can inhibit the

  16. Effects of 14 days of spaceflight and nine days of recovery on cell body size and succinate dehydrogenase activity of rat dorsal root ganglion neurons

    NASA Technical Reports Server (NTRS)

    Ishihara, A.; Ohira, Y.; Roy, R. R.; Nagaoka, S.; Sekiguchi, C.; Hinds, W. E.; Edgerton, V. R.

    1997-01-01

    The cross-sectional areas and succinate dehydrogenase activities of L5 dorsal root ganglion neurons in rats were determined after 14 days of spaceflight and after nine days of recovery. The mean and distribution of the cross-sectional areas were similar to age-matched, ground-based controls for both the spaceflight and for the spaceflight plus recovery groups. The mean succinate dehydrogenase activity was significantly lower in spaceflight compared to aged-matched control rats, whereas the mean succinate dehydrogenase activity was similar in age-matched control and spaceflight plus recovery rats. The mean succinate dehydrogenase activity of neurons with cross-sectional areas between 1000 and 2000 microns2 was lower (between 7 and 10%) in both the spaceflight and the spaceflight plus recovery groups compared to the appropriate control groups. The reduction in the oxidative capacity of a subpopulation of sensory neurons having relatively large cross-sectional areas immediately following spaceflight and the sustained depression for nine days after returning to 1 g suggest that the 0 g environment induced significant alterations in proprioceptive function.

  17. Impaired growth hormone secretion in neonatal hypothyroid rats: hypothalamic versus pituitary component.

    PubMed

    De Gennaro, V; Cella, S G; Bassetti, M; Rizzi, R; Cocchi, D; Muller, E E

    1988-01-01

    In 10-day-old rats made hypothyroid by giving dams propylthiouracil (PTU) in the drinking water since the day of parturition, simultaneous radioimmunoassay (RIA) determinations of basal and stimulated growth hormone (GH) secretion, hypothalamic GH-releasing hormone (GHRH)-like immunoreactivity (LI) content, immunocytochemical localization of somatotrophs, and hypothalamic GHRH-LI-positive structures were performed. The frequency of somatotrophs was also determined. One-day-old hypothyroid rats, whose mothers had been given PTU since the 14th day of pregnancy, were also used for comparison. In 10-day-old hypothyroid rats, pituitary and plasma GH levels and the number of somatotrophs were considerably lower and plasma TSH levels were significantly higher than those in age-matched control rats; however, GHRH-LI titers in the mediobasal hypothalamus and the morphology of GHRH-LI-positive structures were unaltered. In 1-day-old rats the only alteration present, in addition to elevated plasma TSH levels, was a clear-cut decrease in plasma GH levels. An acute challenge with GHRH (20 ng/100 g body wt, sc) or clonidine (15 micrograms/100 g body wt, sc) induced a clear-cut rise in plasma GH levels 15 min postinjection in 10-day-old control rats but failed to do so in age-matched hypothyroid rats. Both compounds failed to rise plasma GH in both hypothyroid and control 1-day-old rats. Taken together these data indicate that in neonatal and infant rats deprivation of thyroid hormones acts primarily to depress pituitary somatotroph function and that possible changes in GHRH-secreting structures represent a later postnatal event. PMID:3124121

  18. Circulating parathyroid hormone and calcitonin in rats after spaceflight

    NASA Technical Reports Server (NTRS)

    Arnaud, Sara B.; Fung, Paul; Popova, Irina A.; Morey-Holton, Emily R.; Grindeland, Richard E.

    1992-01-01

    Parathyroid hormone and calcithonin, two major calcium-regulating hormones, were measured in the plasma of five experimental groups of rats to evaluate postflight calcium homeostasis after the 14-day Cosmos 2044 flight. Parathyroid hormone values were slightly higher in the flight animals (F) than in the appropriate cage and diet controls (S) (44 +/- 21 vs 21 +/- 4 pg/ml, P less than 0.05), but they were the same as in the vivarium controls (V), which had different housing and feeding schedules. The difference in F and V (22 +/- 11 vs 49 +/- 16 pg/ml, P less than 0.05) was most likely due to failure of circulating calcitonin in F to show the normal age-dependent increase which was demonstrated in age-matched controls in a separate experiment. Basal values for parathyroid hormone and calcitonin were unchanged after 2 wk of hindlimb suspension, a flight simulation model, in age-matched and younger rats. From a time course experiment serum calcium was higher and parathyroid hormone lower after 4 wk than in ambulatory controls. Postflight circulating levels of parathyroid hormone appear to reflect disturbances in calcium homeostasis from impaired renal function of undetermined cause, whereas levels of calcitonin reflect depression of a normal growth process.

  19. Clitoria ternatea (Linn) root extract treatment during growth spurt period enhances learning and memory in rats.

    PubMed

    Rai, K S; Murthy, K D; Karanth, K S; Rao, M S

    2001-07-01

    Neonatal rat pups (7 days old) were intubated with either 50 mg/kg body weight or 100 mg/kg body weight of aqueous root extract of Clitoria ternatea (CTR) for 30 days. These rats were then subjected to open field, two compartment passive avoidance and spatial learning (T-Maze) tests (i) immediately after the treatment and (ii) 30 days after the treatment, along with age matched normal and saline control rats. Results showed no change in open field behaviour, but showed improved retention and spatial learning performance at both time points of behavioural tests, indicating the memory enhancing property of CTR which implicates a permanent change in the brain of CTR treated rats. PMID:11881569

  20. Abnormal uterine artery remodelling in the stroke prone spontaneously hypertensive rat

    PubMed Central

    Small, Heather Y.; Morgan, Hannah; Beattie, Elisabeth; Griffin, Sinead; Indahl, Marie; Delles, Christian; Graham, Delyth

    2016-01-01

    Introduction The stroke prone spontaneously hypertensive rat (SHRSP) is an established model of human cardiovascular risk. We sought to characterise the uteroplacental vascular response to pregnancy in this model and determine whether this is affected by the pre-existing maternal hypertension. Methods Doppler ultrasound and myography were utilised to assess uterine artery functional and structural changes pre-pregnancy and at gestational day 18 in SHRSP (untreated and nifedipine treated) and in the normotensive Wistar-Kyoto (WKY) rat. Maternal adaptations to pregnancy were also assessed along with histology and expression of genes involved in oxidative stress in the placenta. Results SHRSP uterine arteries had a pulsatile blood flow and were significantly smaller (70906 ± 3903 μm2 vs. 95656 ± 8524 μm2 cross-sectional area; p < 0.01), had a significant increase in contractile response (57.3 ± 10.5 kPa vs 27.7 ± 1.9 kPa; p < 0.01) and exhibited impaired endothelium-dependent vasorelaxation (58.0 ± 5.9% vs 13.9 ± 4.6%; p < 0.01) compared to WKY. Despite significant blood pressure lowering, nifedipine did not improve uterine artery remodelling, function or blood flow in SHRSP. Maternal plasma sFLT-1/PlGF ratio (5.3 ± 0.3 vs 4.6 ± 0.1; p < 0.01) and the urinary albumin/creatinine ratio (1.9 ± 0.2 vs 0.6 ± 0.1; p < 0.01) was increased in SHRSP vs WKY. The SHRSP placenta had a significant reduction in glycogen cell content and an increase in Hif1α, Sod1 and Vegf. Discussion We conclude that the SHRSP exhibits a number of promising characteristics as a model of spontaneous deficient uteroplacental remodelling that adversely affect pregnancy outcome, independent of pre-existing hypertension. PMID:26612342

  1. Downregulation of vascular soluble guanylate cyclase induced by high salt intake in spontaneously hypertensive rats

    PubMed Central

    Kagota, Satomi; Tamashiro, Akiko; Yamaguchi, Yu; Sugiura, Reiko; Kuno, Takayoshi; Nakamura, Kazuki; Kunitomo, Masaru

    2001-01-01

    Cyclic guanosine monophosphate (cyclic GMP)-mediated mechanism plays an important role in vasodilatation and blood pressure regulation. We investigated the effects of high salt intake on the nitric oxide (NO) – cyclic GMP signal transduction pathway regulating relaxation in aortas of spontaneously hypertensive rats (SHR).Four-week-old SHR and normotensive Wistar-Kyoto rats (WKY) received a normal salt diet (0.3% NaCl) or a high salt diet (8% NaCl) for 4 weeks.In aortic rings from SHR, endothelium-dependent relaxations in response to acetylcholine (ACh), adenosine diphosphate (ADP) and calcium ionophore A23187 were significantly impaired by the high salt intake. The endothelium-independent relaxations in response to sodium nitroprusside (SNP) and nitroglycerin were also impaired, but that to 8-bromo-cyclic GMP remained unchanged. On the other hand, high salt diet had no significant effects on the relaxations of aortic rings from WKY.In aortas from SHR, the release of NO stimulated by ACh was significantly enhanced, whereas the production of cyclic GMP induced by either ACh or SNP was decreased by the high salt intake.Western blot analysis showed that the protein level of endothelial NO synthase (eNOS) was slightly increased, whereas that of soluble guanylate cyclase (sGC) was dramatically reduced by the high salt intake.These results indicate that in SHR, excessive dietary salt can result in downregulation of sGC followed by decreased cyclic GMP production, which leads to impairment of vascular relaxation in responses to NO. It is notable that chronic high salt intake impairs the sGC/cyclic GMP pathway but not the eNOS/NO pathway. PMID:11606313

  2. Diabetes increases susceptibility of primary cultures of rat proximal tubular cells to chemically induced injury

    SciTech Connect

    Zhong Qing; Terlecky, Stanley R.; Lash, Lawrence H.

    2009-11-15

    Diabetic nephropathy is characterized by increased oxidative stress and mitochondrial dysfunction. In the present study, we prepared primary cultures of proximal tubular (PT) cells from diabetic rats 30 days after an ip injection of streptozotocin and compared their susceptibility to oxidants (tert-butyl hydroperoxide, methyl vinyl ketone) and a mitochondrial toxicant (antimycin A) with that of PT cells isolated from age-matched control rats, to test the hypothesis that PT cells from diabetic rats exhibit more cellular and mitochondrial injury than those from control rats when exposed to these toxicants. PT cells from diabetic rats exhibited higher basal levels of reactive oxygen species (ROS) and higher mitochondrial membrane potential, demonstrating that the PT cells maintain the diabetic phenotype in primary culture. Incubation with either the oxidants or mitochondrial toxicant resulted in greater necrotic and apoptotic cell death, greater evidence of morphological damage, greater increases in ROS, and greater decreases in mitochondrial membrane potential in PT cells from diabetic rats than in those from control rats. Pretreatment with either the antioxidant N-acetyl-L-cysteine or a catalase mimetic provided equivalent protection of PT cells from both diabetic and control rats. Despite the greater susceptibility to oxidative and mitochondrial injury, both cytoplasmic and mitochondrial glutathione concentrations were markedly higher in PT cells from diabetic rats, suggesting an upregulation of antioxidant processes in diabetic kidney. These results support the hypothesis that primary cultures of PT cells from diabetic rats are a valid model in which to study renal cellular function in the diabetic state.

  3. Nicotine-induced behavioral sensitization in an adult rat model of attention deficit/hyperactivity disorder (ADHD).

    PubMed

    Watterson, Elizabeth; Spitzer, Alexander; Watterson, Lucas R; Brackney, Ryan J; Zavala, Arturo R; Olive, M Foster; Sanabria, Federico

    2016-10-01

    Attention deficit hyperactivity disorder (ADHD) is associated with increased risk of tobacco dependence. Nicotine, the main psychoactive component of tobacco, appears to be implicated in ADHD-related tobacco dependence. However, the behavioral responsiveness to nicotine of the prevalent animal model of ADHD, the spontaneously hypertensive rat (SHR), is currently underinvestigated. The present study examined the activational effects of acute and chronic nicotine on the behavior of adult male SHRs, relative to Wistar Kyoto (WKY) controls. Experiment 1 verified baseline strain differences in open-field locomotor activity. Experiment 2 tested for baseline strain differences in rotational behavior using a Rotorat apparatus. Adult SHR and WKY rats were then exposed to a 7-day regimen of 0.6mg/kg/d s.c. nicotine, or saline, prior to each assessment. A separate group of SHRs underwent similar training, but was pre-treated with mecamylamine, a cholinergic antagonist. Nicotine sensitization, context conditioning, and mecamylamine effects were then tested. Baseline strain differences were observed in open-field performance and in the number of full rotations in the Rotorat apparatus, but not in the number of 90° rotations or direction changes. In these latter measures, SHRs displayed weaker nicotine-induced rotational suppression than WKYs. Both strains expressed nicotine-induced sensitization of rotational activity, but evidence for strain differences in sensitization was ambiguous; context conditioning was not observed. Mecamylamine reversed the effects of nicotine on SHR performance. These findings are consistent with the hypothesis that a reduced aversion to nicotine (expressed in rats as robust locomotion) may facilitate smoking among adults with ADHD. PMID:27363925

  4. Hydrogen sulphide and tempol treatments improve the blood pressure and renal excretory responses in spontaneously hypertensive rats.

    PubMed

    Ahmad, Fiaz Ud Din; Sattar, Munavvar A; Rathore, Hassaan A; Tan, Yong Chia; Akhtar, Safia; Jin, Oh Hui; Pei, Yen Pei; Abdullah, Nor A; Johns, Edward J

    2014-05-01

    Oxidative stress and suppressed H2S production lead to increased renal vascular resistance, disturbed glomerular hemodynamics, and abnormal renal sodium and water handling, contribute to the pathogenesis and maintenance of essential hypertension in man and the spontaneously hypertensive rat. This study investigated the impact of H2S and tempol alone and in combination on blood pressure and renal hemodynamics and excretory functions in the SHR. Groups of WKY rats or SHR (n=6) were treated for 4 weeks either as controls or received NaHS (SHR+NaHS), tempol (SHR+Tempol), or NaHS plus tempol (SHR+NaHS +Tempol). Metabolic studies were performed on days 0, 14, and 28, thereafter animals were anaesthetized to measure renal hemodynamics and plasma oxidative and antioxidant markers. SHR control rats had higher mean arterial blood pressure (140.0 ± 2 vs. 100.0 ± 3 mmHg), lower plasma and urinary H2S, creatinine clearance, urine flow rate and urinary sodium excretion, and oxidative stress compared to WKY (all p<0.05). Treatment either with NaHS or with tempol alone decreased blood pressure and oxidative stress and improved renal hemodynamic and excretory function compared to untreated SHR. Combined NaHS and tempol therapy in SHRs caused larger decreases in blood pressure (∼20-22% vs. ∼11-15% and ∼10-14%), increases in creatinine clearance, urinary sodium excretion and fractional sodium excretion and up-regulated the antioxidant status compared to each agent alone (all p<0.05). These findings demonstrated that H2S and tempol together resulted in greater reductions in blood pressure and normalization of kidney function compared with either compound alone. PMID:24502512

  5. α2-Adrenoreceptor Constraint of Catecholamine Release and Blood Pressure Is Enhanced in Female Spontaneously Hypertensive Rats

    PubMed Central

    Berg, Torill

    2016-01-01

    α2-adrenoceptors (α2AR) lower central sympathetic output and peripheral catecholamine release, and may therefore prevent sympathetic hyperactivity and hypertension. The α2AR are dysfunctional in male spontaneously hypertensive rats (SHR). Premenopausal females are less hypertensive than males. The purpose of this study was to test if this difference could be explained by functional α2AR in the female SHR. A 15-min tyramine-infusion was used to stimulate norepinephrine release through the re-uptake transporter, consequently preventing re-uptake. Presynaptic control of vesicular release will therefore be reflected as differences in overflow to plasma. The surgical trauma activates secretion of epinephrine, also subjected to α2AR auto-inhibition. Blood pressure was monitored through a femoral artery catheter and cardiac output by ascending aorta flow in 12-14 weeks-old (early hypertension) SHR and normotensive rats (WKY). Total peripheral vascular resistance (TPR) was calculated. Female SHR, unlike male, were close to normotensive. Pre-treatment with none-selective (clonidine) or non-A-selective (ST-91) α2AR agonist reduced, and none-selective α2AR antagonist (L-659,066) increased tyramine-induced norepinephrine overflow in female WKY and SHR. L-659,066 also increased secretion of epinephrine. The L-659,066-induced increase in catecholamine release was further enhanced by additional pre-treatment with ST-91 or angiotensin AT1 receptor antagonist (losartan) in SHR only. L-659,066 eliminated the tyramine-induced rise in TPR in both strains in female rats. Conclusion: α2AR-mediated control of catecholamine release and vascular tension was therefore functional in female SHR, unlike that previously observed in male SHR. Functional α2AR is likely to have a protective function and may explain the lack of hypertension in the young female SHR. PMID:27065790

  6. Strain differences in sensitivity of rats to Mycoplasma arthritidis ISR 1 infection are under multiple gene control.

    PubMed Central

    Binder, A; Gärtner, K; Hedrich, H J; Hermanns, W; Kirchhoff, H; Wonigeit, K

    1990-01-01

    At least 5 female rats from each of 24 inbred (ACI, AS, BDIX, BH, BN, BS, BUF, DA, LE, LEW, MWF, OM, SPRD-Cu3, W-Krypt, and WKY), RT1 congenic [BH.1L(LEW), LEW.1A(AVN), LEW.1C(WIST), LEW.1LV3(BH), LEW.1K(SHR), and LEW.1N(BN)], and F1 hybrid [(LEW x BN)F1, (LEW.1W x LEW.1A)F1, and (LEW x LEW.1W)F1] strains, representing eight independent major histocompatibility complex (MHC) haplotypes (a, b, c, dv1, k, l, n, and u) and five related RT1 haplotypes (av1, lv1, lv3, uv2, and uv3), were inoculated intravenously with Mycoplasma arthritidis, and the severity of the polyarthritis that developed was determined by estimating arthritis scores and weight reductions. The 24 inbred, congenic, and F1 hybrid rat strains differed considerably in their sensitivity to infection with M. arthritidis and in the severity of the polyarthritis that they developed. Statistical evaluation showed that in the acute phase (days 1 to 42 after infection) as well as in the chronic phase (days 39 to 121 after infection) of the disease, the means of the arthritis scores for the strains form a continuous variation without significant interruptions, with the very sensitive LEW rats, the RT1 congenic rats on LEW background, the F1 hybrids with LEW, and the MWF, BS, BH, and DA rats on one end and the resistant WKY, BUF, W-Krypt, LE, and OM rats on the other end. A continuous variation was also observed for the means of the growth rates. There were, however, no significant differences between the sensitive and the resistant rat strains in the antibody titers determined by complement fixation test and enzyme immunoassay. Heritabilities of arthritis scores were calculated for all strains (h2 = 0.39 to 0.62), for the RT1 congenic strains (h2 = 0.04 to 0.14), and for several strains with identical MHC genes (h2 = 0.61 to 0.93). The results show that non-MHC genes are probably responsible for the sensitivity of rats to infection with M. arthritidis. PMID:2111282

  7. Enhanced inflammatory response to acute ozone exposure in rats during pregnancy and lactation

    SciTech Connect

    Gunnison, A.F.; Weideman, P.A.; Sobo, M. )

    1992-11-01

    Experimental evidence from several studies suggests that pregnant animals and women are more susceptible to oxidants than nonpregnant controls. In the study reported here, we sought to determine whether pregnant rats are more sensitive than age-matched virgin females to the inflammatory effects of ozone, a gaseous oxidant of considerable environmental significance. Rats at several stages of pregnancy and lactation, as well as age-matched virgin females, were exposed to 1 ppm ozone for 6 hr. Controls were sham-exposed to pure air for an identical period of time. Bronchoalveolar lavage was performed 24 hr after the beginning of exposure, and components of the lavage fluid considered to be indicators of inflammation were used to assess the severity of pulmonary inflammation. The results of this experiment showed that significantly enhanced sensitivity to ozone-induced pulmonary inflammation develops during pregnancy, is maintained during lactation, and disappears following lactation. Implicit in this pattern of differential sensitivity in rats is the possibility of a similar pattern of inflammatory response in analogous groups of humans as well as the potential for applicability to other oxidative pollutants.

  8. Quercetin, a flavonoid antioxidant, modulates endothelium-derived nitric oxide bioavailability in diabetic rat aortas.

    PubMed

    Machha, Ajay; Achike, Francis I; Mustafa, Ali Mohd; Mustafa, Mohd Rais

    2007-06-01

    The present work examined the effect of chronic oral administration of quercetin, a flavonoid antioxidant, on blood glucose, vascular function and oxidative stress in STZ-induced diabetic rats. Male Wistar-Kyoto (WKY) rats were randomized into euglycemic, untreated diabetic, vehicle (1% w/v methylcellulose)-treated diabetic, which served as control, or quercetin (10mgkg(-1) body weight)-treated diabetic groups and treated orally for 6 weeks. Quercetin treatment reduced blood glucose level in diabetic rats. Impaired relaxations to endothelium-dependent vasodilator acetylcholine (ACh) and enhanced vasoconstriction responses to alpha(1)-adrenoceptor agonist phenylephrine (PE) in diabetic rat aortic rings were restored to euglycemic levels by quercetin treatment. Pretreatment with N(omega)-nitro-l-arginine methyl ester (l-NAME, 10microM) or methylene blue (10microM) completely blocked but indomethacin (10microM) did not affect relaxations to ACh in aortic rings from vehicle- or quercetin-treated diabetic rats. PE-induced vasoconstriction with an essentially similar magnitude in vehicle- or quercetin-treated diabetic rat aortic rings pretreated with l-NAME (10microM) plus indomethacin (10microM). Quercetin treatment reduced plasma malonaldehyde (MDA) plus 4-hydroxyalkenals (4-HNE) content as well as increased superoxide dismutase activity and total antioxidant capacity in diabetic rats. From the present study, it can be concluded that quercetin administration to diabetic rats restores vascular function, probably through enhancement in the bioavailability of endothelium-derived nitric oxide coupled to reduced blood glucose level and oxidative stress. PMID:17513143

  9. Pathological role of a constitutively active population of alpha(1D)-adrenoceptors in arteries of spontaneously hypertensive rats.

    PubMed

    Gisbert, Regina; Ziani, Khalid; Miquel, Raquel; Noguera, M Antonia; Ivorra, M Dolores; Anselmi, Elsa; D'Ocon, Pilar

    2002-01-01

    1. The role of a constitutively active population of alpha(1D)-adrenoceptors was analysed in arteries obtained from spontaneously hypertensive rats (SHR) and controls (WKY) divided into three groups: young prehypertensive, adult hypertensive, and adult animals chronically treated with captopril (50 mg kg(-1) per day orally) in order to prevent the hypertensive state. 2. In adult SHR, a significant increase in BMY 7378 potency (not in prazosin potency) was observed in aorta, mesenteric artery, and the first and second branches of the small mesenteric arteries with respect to WKY rats. This difference was not observed in iliac and tail arteries, which suggests an increased functional role of alpha(1D)-adrenoceptors only in some vessels of SHR. 3. The increase in the resting tone (IRT) observed in absence of agonist, inhibited by BMY 7378, that represents the constitutively active population of alpha(1D)-adrenoceptors, was also significantly greater in aorta and mesenteric artery from adult SHR. 4. In young and captopril treated adult animals, no differences between strains with respect to BMY 7378 potency, or IRT were observed. 5. The increase in the functional role of alpha(1D)-adrenoceptors and their constitutive activity observed in hypertension is prevented by captopril treatment. The pathological consequence of this change is the slower rate of recovery of the basal tone after removal of an adrenergic stimulus, observed in vessels from hypertensive animals that had shown an increase in the functionality of constitutively active alpha(1D)-adrenoceptors. This change was not observed in prehypertensive or captopril treated animals. PMID:11786496

  10. Pathological role of a constitutively active population of α1D-adrenoceptors in arteries of spontaneously hypertensive rats

    PubMed Central

    Gisbert, Regina; Ziani, Khalid; Miquel, Raquel; Noguera, M Antonia; Ivorra, M Dolores; Anselmi, Elsa; D'Ocon, Pilar

    2002-01-01

    The role of a constitutively active population of α1D-adrenoceptors was analysed in arteries obtained from spontaneously hypertensive rats (SHR) and controls (WKY) divided into three groups: young prehypertensive, adult hypertensive, and adult animals chronically treated with captopril (50 mg kg−1 per day orally) in order to prevent the hypertensive state.In adult SHR, a significant increase in BMY 7378 potency (not in prazosin potency) was observed in aorta, mesenteric artery, and the first and second branches of the small mesenteric arteries with respect to WKY rats. This difference was not observed in iliac and tail arteries, which suggests an increased functional role of α1D-adrenoceptors only in some vessels of SHR.The increase in the resting tone (IRT) observed in absence of agonist, inhibited by BMY 7378, that represents the constitutively active population of α1D-adrenoceptors, was also significantly greater in aorta and mesenteric artery from adult SHR.In young and captopril treated adult animals, no differences between strains with respect to BMY 7378 potency, or IRT were observed.The increase in the functional role of α1D-adrenoceptors and their constitutive activity observed in hypertension is prevented by captopril treatment. The pathological consequence of this change is the slower rate of recovery of the basal tone after removal of an adrenergic stimulus, observed in vessels from hypertensive animals that had shown an increase in the functionality of constitutively active α1D-adrenoceptors. This change was not observed in prehypertensive or captopril treated animals. PMID:11786496

  11. Pioglitazone treatment increases COX-2-derived prostacyclin production and reduces oxidative stress in hypertensive rats: role in vascular function

    PubMed Central

    Hernanz, Raquel; Martín, Ángela; Pérez-Girón, Jose V; Palacios, Roberto; Briones, Ana M; Miguel, Marta; Salaices, Mercedes; Alonso, María J

    2012-01-01

    BACKGROUND AND PURPOSE PPARγ agonists, glitazones, have cardioprotective and anti-inflammatory actions associated with gene transcription interference. In this study, we determined whether chronic treatment of adult spontaneously hypertensive rats (SHR) with pioglitazone alters BP and vascular structure and function, and the possible mechanisms involved. EXPERIMENTAL APPROACH Mesenteric resistance arteries from untreated or pioglitazone-treated (2.5 mg·kg−1·day−1, 28 days) SHR and normotensive [Wistar Kyoto (WKY)] rats were used. Vascular structure was studied by pressure myography, vascular function by wire myography, protein expression by Western blot and immunohistochemistry, mRNA levels by RT-PCR, prostanoid levels by commercial kits and reactive oxygen species (ROS) production by dihydroethidium-emitted fluorescence. KEY RESULTS In SHR, pioglitazone did not modify either BP or vascular structural and mechanical alterations or phenylephrine-induced contraction, but it increased vascular COX-2 levels, prostacyclin (PGI2) production and the inhibitory effects of NS 398, SQ 29,548 and tranylcypromine on phenylephrine responses. The contractile phase of the iloprost response, which was reduced by SQ 29,548, was greater in pioglitazone-treated and pioglitazone-untreated SHR than WKY. In addition, pioglitazone abolished the increased vascular ROS production, NOX-1 levels and the inhibitory effect of apocynin and allopurinol on phenylephrine contraction, whereas it did not modify eNOS expression but restored the potentiating effect of N-nitro-L-arginine methyl ester on phenylephrine responses. CONCLUSIONS AND IMPLICATIONS Although pioglitazone did not reduce BP in SHR, it increased COX-2-derived PGI2 production, reduced oxidative stress, and increased NO bioavailability, which are all involved in vasoconstrictor responses in resistance arteries. These effects would contribute to the cardioprotective effect of glitazones reported in several pathologies. PMID

  12. Aldosterone alters the participation of endothelial factors in noradrenaline vasoconstriction differently in resistance arteries from normotensive and hypertensive rats.

    PubMed

    Xavier, Fabiano E; Blanco-Rivero, Javier; Avendaño, María Soledad; Sastre, Esther; Yela, Rubén; Velázquez, Kyra; Salaíces, Mercedes; Balfagón, Gloria

    2011-03-11

    This study analyzed the effect of aldosterone (0.05mg/kg per day, 3 weeks) on vasoconstriction induced by noradrenaline in mesenteric resistance arteries from WKY rats and SHR. Contraction to noradrenaline was measured in mesenteric resistance arteries from untreated and aldosterone-treatedrats from both strains. Participation of nitric oxide (NO), superoxide anions, thromboxane A(2) (TxA(2)) and prostacyclin in this response was determined. 6-keto-prostaglandin (PG)F1alpha and thromboxane B(2) (TxB(2)) releases were determined by enzyme immunoassay. NO and superoxide anion release were also determined by fluorescence and chemiluminiscence, respectively. Aldosterone did not modify noradrenaline-induced contraction in either strain. In mesenteric resistance arteries from both aldosterone-treated groups, endothelium removal or preincubation with NO synthesis inhibitor L-NAME increased the noradrenaline-induced contraction, while incubation with the superoxide anion scavenger tempol decreased it. Preincubation with either the COX-1/2 or COX-2 inhibitor (indomethacin and NS-398, respectively) decreased the noradrenaline contraction in aldosterone-treated animals, while this response was not modified by COX-1 inhibitor SC-560. TxA(2) synthesis inhibitor (furegrelate), or TxA2 receptor antagonist (SQ 29 548) also decreased the noradrenaline contraction in aldosterone-treated animals. In untreated SHR, but not WKY rats, this response was increased by L-NAME, and reduced by tempol, indomethacin, NS-398 or SQ 29 548. Aldosterone treatment did not modify NO or TxB(2) release, but it did increase superoxide anion and 6-keto-PGF(1alpha) release in mesenteric resistance arteries from both strains. In conclusion, chronic aldosterone treatment reduces smooth muscle contraction to alpha-adrenergic stimuli, producing a new balance in the release of endothelium-derived prostanoids and NO. PMID:21262224

  13. Berberine attenuates intestinal disaccharidases in streptozotocin-induced diabetic rats.

    PubMed

    Liu, Li; Deng, Yuanxiong; Yu, Sen; Lu, Shousi; Xie, Lin; Liu, Xiaodong

    2008-05-01

    Previous studies demonstrated anti-diabetic effects of berberine. However, the facts that berberine had low bioavailability and poor absorption through the gut wall indicated that berberine might exert its antihyperglycaemic effect in the intestinal tract before absorption. The purpose of this study was to investigate whether berberine attenuates disaccharidase activities and beta-glucuronidase activity in the small intestine of streptozotocin (STZ)-induced diabetic rats. Two groups of STZ-induced diabetic rats were treated with protamine zinc insulin (10 U/Kg) subcutaneously twice daily and berberine (100 mg/Kg) orally once daily for 4 weeks, respectively. Both age-matched normal rats and diabetic control rats received physiological saline only. Fasting blood glucose levels, body weight, intestinal disaccharidase and beta-glucuronidase activities in duodenum, jejunum and ileum were assessed for changes. Our findings suggested that berberine treatment significantly decreases the activities of intestinal disaccharidases and beta-glucuronidase in STZ-induced diabetic rats. The results demonstrated that the inhibitory effect on intestinal disaccharidases and beta-glucuronidase of berberine might be one of the mechanisms for berberine as an antihyperglycaemic agent. PMID:18557425

  14. Ergonomic task reduction prevents bone osteopenia in a rat model of upper extremity overuse

    PubMed Central

    BARBE, Mary F.; JAIN, Nisha X.; MASSICOTTE, Vicky S.; POPOFF, Steven N.; BARR-GILLESPIE, Ann E.

    2015-01-01

    We evaluated the effectiveness of ergonomic workload reduction of switching rats from a high repetition high force (HRHF) lever pulling task to a reduced force and reach rate task for preventing task-induced osteopenic changes in distal forelimb bones. Distal radius and ulna trabecular structure was examined in young adult rats performing one of three handle-pulling tasks for 12 wk: 1) HRHF, 2) low repetition low force (LRLF); or 3) HRHF for 4 wk and than LRLF thereafter (HRHF-to-LRLF). Results were compared to age-matched controls rats. Distal forelimb bones of 12-wk HRHF rats showed increased trabecular resorption and decreased volume, as control rats. HRHF-to-LRLF rats had similar trabecular bone quality as control rats; and decreased bone resorption (decreased trabecular bone volume and serum CTX1), increased bone formation (increased mineral apposition, bone formation rate, and serum osteocalcin), and decreased osteoclasts and inflammatory cytokines, than HRHF rats. Thus, an ergonomic intervention of HRHF-to-LRLF prevented loss of trabecular bone volume occurring with prolonged performance of a repetitive upper extremity task. These findings support the idea of reduced workload as an effective approach to management of work-related musculoskeletal disorders, and begin to define reach rate and load level boundaries for such interventions. PMID:25739896

  15. Improving Bone Microarchitecture in Aging with Diosgenin Treatment: A Study in Senescence-Accelerated OXYS Rats.

    PubMed

    Tikhonova, Maria A; Ting, Che-Hao; Kolosova, Nataliya G; Hsu, Chao-Yu; Chen, Jian-Horng; Huang, Chi-Wen; Tseng, Ging-Ting; Hung, Ching-Sui; Kao, Pan-Fu; Amstislavskaya, Tamara G; Ho, Ying-Jui

    2015-10-31

    Osteoporosis is a major disease associated with aging. We have previously demonstrated that diosgenin prevents osteoporosis in both menopause and D-galactose-induced aging rats. OXYS rats reveal an accelerated senescence and are used as a suitable model of osteoporosis. The aim of the present study was to analyze microarchitecture and morphological changes in femur of OXYS rats using morphological tests and microcomputed tomography scanning, and to evaluate the effects of oral administration of diosgenin at 10 and 50 mg/kg/day on femur in OXYS rats. The result showed that, compared with age-matched Wistar rats, the femur of OXYS rats revealed lower bone length, bone weight, bone volume, frame volume, frame density, void volume, porosity, external and internal diameters, cortical bone area, BV/TV, Tb.N, and Tb.Th, but higher Tb.Sp. Eight weeks of diosgenin treatment decreased porosity and Tb.Sp, but increased BV/TV, cortical bone area, Tb.N and bone mineral density, compared with OXYS rats treated with vehicle. These data reveal that microarchitecture and morphological changes in femur of OXYS rats showed osteoporotic aging features and suggest that diosgenin may have beneficial effects on aging-induced osteoporosis. PMID:26387656

  16. Comparison of calcium import as a function of contraction in the aortic smooth muscle of Sprague-Dawley, Wistar Kyoto and spontaneously hypertensive rats.

    PubMed

    Rahmani, M A; DeGray, G; David, V; Ampy, F R; Jones, L

    1999-04-15

    Genetic variations of far-reaching consequences have been established between spontaneously hypertensive rats (SHR) and their controls, Wistar Kyoto rats (WKY). The SHR strain is the most widely used model for the study of genetic hypertension. Calcium homeostasis in the vascular smooth muscle (VSM) is controlled by calcium channels and calcium pumps located in both VSM and the overlying endothelial cells that line the large blood vessels and the heart. Hypertension adversely affects calcium homeostasis. Investigations on the import of calcium from extracellular spaces with alpha1-adrenergic stimulation as a function of contractility of VSM cells in SHR and WKY were made and compared with the contractility observed in VSM cells of Sprague-Dawley (CD) rats. Experiments were performed on rings from thoracic aortas of three strains with endothelial lining intact or removed to discern the paracrine control of endothelium on contractility in response to calcium import. The internal stores of Ca2+ were depleted by repeated alpha 1-adrenergic stimulation with phenylephrine (PE) and refilling of these stores was prevented by cyclopiazonic acid (CPA) and/or thapsigargin (TG), two known inhibitors of Ca2+ATPase, the enzyme that drives sarcoplasmic calcium pumps. The two components of tonic muscular contraction, T I and T II, which are known to be due to the flow of Ca2+ from the extracellular gradient controlled via the poly-phosphoinositide cascade and nifedipine sensitive Ca2+ channels were found to be variable among these strains. Implications of these variations are discussed in this report PMID:10209059

  17. The importance of the selection of appropriate reference genes for gene expression profiling in adrenal medulla or sympathetic ganglia of spontaneously hypertensive rat.

    PubMed

    Vavřínová, A; Behuliak, M; Zicha, J

    2016-07-18

    Catecholaminergic system plays an important role in hypertension development. The available results on mRNA expression of catecholaminergic system genes in spontaneously hypertensive rats (SHR) are often contradictory. One of the possible causes might be the use of various reference genes as internal controls. In the present study, we searched for suitable reference genes in adrenal medulla or sympathetic ganglia of SHR and Wistar-Kyoto (WKY) rats, which would enable reliable comparison of mRNA expression between these two strains. The mRNA expression was measured by quantitative real-time PCR in adrenal medulla and superior cervical ganglia of 4-week-old or 24-week-old SHR and WKY rats. We evaluated 12 reference genes by three software tools (Normfinder, BestKeeper, geNorm) and compared them for the standardization of mRNA expression. Combination of reference genes Hprt1 and Ywhaz in adrenal medulla and Gapdh and 18S in sympathetic ganglia were chosen as the best ones. 18S was found as applicable reference gene in both tissues. We found many alterations in expression of catecholaminergic system genes in adrenal medulla and sympathetic ganglia of SHR. The usage of the most or the least stable reference gene as internal control changed results moderately in sympathetic ganglia but seriously in adrenal medulla. For example, tyrosine hydroxylase (Th) gene was underexpressed in adrenal medulla of adult SHR using the appropriate reference gene but unchanged after the standardization to the least stable reference gene. Our results indicate the importance of appropriate internal control. The suitability of reference genes should be checked again in the case of change in experimental conditions. PMID:27070752

  18. Cerebral angiography, blood flow and vascular reactivity in progressive hypertension

    PubMed Central

    Li, Yunxia; Shen, Qiang; Huang, Shiliang; Li, Wei; Muir, Eric R.; Long, Justin; Duong, Timothy Q.

    2015-01-01

    Chronic hypertension alters cerebral vascular morphology, cerebral blood flow (CBF), cerebrovascular reactivity, increasing susceptibility to neurological disorders. This study evaluated: i) the lumen diameters of major cerebral and downstream arteries using magnetic resonance angiography, and ii) basal CBF, and iii) cerebrovascular reactivity to hypercapnia of multiple brain regions using arterial-spin-labeling technique in spontaneously hypertensive rats (SHR) at different stages. Comparisons were made with age-matched normotensive Wistar Kyoto (WKY) rats. In 10-week SHR, lumen diameter started to reduce, basal CBF, and hypercapnic CBF response were higher from elevated arterial blood pressure, but there was no evidence of stenosis, compared to age-matched WKY. In 20-week SHR, lumen diameter remained reduced, CBF returned toward normal from vasoconstriction, hypercapnic CBF response reversed and became smaller, but without apparent stenosis. In 40-week SHR, lumen diameter remained reduced and basal CBF further decreased, resulting in larger differences compared to WKY. There was significant stenosis in main supplying cerebral vessels. Hypercapnic CBF response further decreased, with some animals showing negative hypercapnic CBF responses in some brain regions, indicative of compromised cerebrovascular reserve. The territory with negative hypercapnia CBF responses corresponded with the severity of stenosis in arteries that supplied those territories. We also found enlargement of downstream vessels and formation of collateral vessels as compensatory responses to vasoconstriction upstream vessels. The middle cerebral and azygos arteries were amongst the most susceptible to hypertension-induced changes. Multimodal MRI provides clinically relevant data that might be useful to characterize disease pathogenesis, stage disease progression, and monitor treatment effects in hypertension. PMID:25731987

  19. Lack of nitric oxide- and guanosine 3′:5′-cyclic monophosphate-dependent regulation of α-thrombin-induced calcium transient in endothelial cells of spontaneously hypertensive rat hearts

    PubMed Central

    Failli, Paola; Fazzini, Alessandro; Ruocco, Carlo; Mazzetti, Luca; Cecchi, Enrica; Giovannelli, Lisa; Marra, Fabio; Milani, Stefano; Giotti, Alberto

    2000-01-01

    While the expression and/or activity of endothelial nitric oxide synthase (eNOS) has been characterized in spontaneously hypertensive (SHR) and normotensive Wistar Kyoto rat (WKY) hearts, in coronary endothelial cells (ECs) from both strains, the effect of NO on intracellular calcium concentration ([Ca2+]i) is still unknown. Coronary microvascular ECs were isolated from SHR and WKY and characterized. Immunocytochemistry and Western blot analysis showed that eNOS was similarly expressed in ECs from both strains. Measuring [Ca2+]i by imaging analysis of fura-2-loaded cells, we demonstrated that α-thrombin (3−180 U l−1) induced a superimposable dose-dependent calcium transient in ECs from both strains. In WKY ECs, S-nitroso-N-acetyl-DL-penicillamine (SNAP) dose-dependently (10–100 μM) and 0.1 μM atrial natriuretic factor (ANF) reduced the maximum and the decay time of α-thrombin-induced calcium transient. The inhibitory effects of SNAP and ANF were prevented by blocking cyclic GMP-dependent protein kinase. Non selective eNOS inhibitors prolonged the decay time of α-thrombin-induced calcium transient, while the selective inducible NOS inhibitor 1400 W was ineffective. SNAP (100 μM) and 0.1 μM ANF increased cyclic GMP content up to 22.9 and 42.3 fold respectively. In SHR ECs, α-thrombin-induced calcium transient was not modified by SNAP, ANF or eNOS inhibition. SNAP (100 μM) and 0.1 μM ANF increased cyclic GMP content up to 9.3 and 51 fold respectively. In WKY ECs, SNAP dose-dependently (10–100 μM) reduced also bradykinin-induced calcium transient, while in SHR ECs was ineffective. We concluded that in SHR ECs, the cyclic GMP-dependent regulation of calcium transient is lost. PMID:10928946

  20. Fine-mapping diabetes-related traits, including insulin resistance, in heterogeneous stock rats.

    PubMed

    Solberg Woods, Leah C; Holl, Katie L; Oreper, Daniel; Xie, Yuying; Tsaih, Shirng-Wern; Valdar, William

    2012-11-01

    Type 2 diabetes (T2D) is a disease of relative insulin deficiency resulting from both insulin resistance and beta cell failure. We have previously used heterogeneous stock (HS) rats to fine-map a locus for glucose tolerance. We show here that glucose intolerance in the founder strains of the HS colony is mediated by different mechanisms: insulin resistance in WKY and an insulin secretion defect in ACI, and we demonstrate a high degree of variability for measures of insulin resistance and insulin secretion in HS rats. As such, our goal was to use HS rats to fine-map several diabetes-related traits within a region on rat chromosome 1. We measured blood glucose and plasma insulin levels after a glucose tolerance test in 782 male HS rats. Using 97 SSLP markers, we genotyped a 68 Mb region on rat chromosome 1 previously implicated in glucose and insulin regulation. We used linkage disequilibrium mapping by mixed model regression with inferred descent to identify a region from 198.85 to 205.9 that contains one or more quantitative trait loci (QTL) for fasting insulin and a measure of insulin resistance, the quantitative insulin sensitivity check index. This region also encompasses loci identified for fasting glucose and Insulin_AUC (area under the curve). A separate <3 Mb QTL was identified for body weight. Using a novel penalized regression method we then estimated effects of alternative haplotype pairings under each locus. These studies highlight the utility of HS rats for fine-mapping genetic loci involved in the underlying causes of T2D. PMID:22947656

  1. Bilateral common carotid artery stenosis in normotensive rats impairs endothelium-dependent dilation of parenchymal arterioles.

    PubMed

    Matin, Nusrat; Fisher, Courtney; Jackson, William F; Dorrance, Anne M

    2016-05-15

    Chronic cerebral hypoperfusion is a risk factor for cognitive impairment. Reduced blood flow through the common carotid arteries induced by bilateral carotid artery stenosis (BCAS) is a physiologically relevant model of chronic cerebral hypoperfusion. We hypothesized that BCAS in 20-wk-old Wistar-Kyoto (WKY) rats would impair cognitive function and lead to reduced endothelium-dependent dilation and outward remodeling in the parenchymal arterioles (PAs). After 8 wk of BCAS, both short-term memory and spatial discrimination abilities were impaired. In vivo assessment of cerebrovascular reserve capacity showed a severe impairment after BCAS. PA endothelial function and structure were assessed by pressure myography. BCAS impaired endothelial function in PAs, as evidenced by reduced dilation to carbachol. Addition of nitric oxide synthase and cyclooxygenase inhibitors did not change carbachol-mediated dilation in either group. Inhibiting CYP epoxygenase, the enzyme that produces epoxyeicosatrienoic acid (EETs), a key determinant of endothelium-derived hyperpolarizing factor (EDHF)-mediated dilation, abolished dilation in PAs from Sham rats, but had no effect in PAs from BCAS rats. Expression of TRPV4 channels, a target for EETs, was decreased and maximal dilation to a TRPV4 agonist was attenuated after BCAS. Together these data suggest that EET-mediated dilation is impaired in PAs after BCAS. Thus impaired endothelium-dependent dilation in the PAs may be one of the contributing factors to the cognitive impairment observed after BCAS. PMID:26968546

  2. Agonist-induced activation of rat mesenteric resistance vessels: comparison between noradrenaline and vasopressin

    SciTech Connect

    Cauvin, C.; Weir, S.W.; Wallnoefer, A.R.; Rueegg, U.P.

    1988-01-01

    The effects of noradrenaline (NA, 10(-5) M) and (arginine8)vasopressin (AVP, 10(-7) M) on tension in Ca2+-free medium and on membrane potential, and the inhibition of NA- and AVP-induced contractions by isradipine, have been compared in mesenteric resistance vessels (MRVs) from Wistar-Kyoto (WKY) rats. The release of intracellular Ca2+ by AVP contributed significantly less to its tension development than does that by NA. Nonetheless, the concentration-response curves for inhibition by isradipine of NA- and AVP-induced tonic tension were nearly identical. Similarly, these two agonists produced the same degree of membrane depolarization. In addition, both agonists were able to stimulate large contractions in vessels previously depolarized by 80 mM K+. AVP also stimulated /sup 45/Ca influx into rat cultured aortic smooth muscle cells. In contrast to the stimulation of /sup 45/Ca influx by KCl depolarization, the agonist-stimulated /sup 45/Ca influx was insensitive to inhibition by organic Ca2+ antagonists. It is concluded that Ca2+ entry through receptor-operated Ca2+-permeable channels (ROCs) may contribute to agonist-induced activation of rat aortic and MRV smooth muscle.

  3. Experiment K-6-05. The maturaton of bone and dentin matrices in rats flown on Cosmos 1887

    NASA Technical Reports Server (NTRS)

    Simmons, D.; Grynpas, M.; Rosenberg, G.; Durnova, G.

    1990-01-01

    The chemistry, hydroxyapatite crystal size, and maturation of the bone and dentin is characterized in rats exposed to microgravity for 12.5d in a Soviet Biosatellite (Cosmos-1887). Calvarial and vertebral bone ash was subnormal, but contained a normal percent composition of Ca, P, and Mg. These tissues varied from the norm by having lower Ca/P and higher Ca/Mg ratios than any of their age-matched controls (Vivarium and Synchronous Groups). Gradient density analyses (calvaria) indicated a strong shift to the lower sp.gr. fractions which was commensurate with impaired rates of matrix-mineral maturation. X-ray diffraction data were confirmatory. Bone hydroxyapatite crystal growth in Flight rats was preferentially altered in a way to reduce the dimension of their C-axis. Flight rat dentin was normal with respect to age-matched control Ca, P, Mg, and Zn concentrations and their Ca/P and Ca/Mg ratios. These observations affirm the concept that microgravity adversely affects the maturation of newly formed matrix and mineral moieties in bone.

  4. Tactile stimulation during development alters the neuroanatomical organization of the optic nerve in normal rats.

    PubMed

    Horiquini-Barbosa, Everton; Lachat, João-José

    2016-06-01

    This study was designed to investigate the progressive effect of tactile stimulation in the cytoarchitecture of the optic nerve of normal rats during early postnatal development. We used 36 male pups which were randomly assigned to either the tactile-stimulated group (TS-stimulation for 3 min, once a day, from postnatal day (P) 1 to 32) or the non-tactile-stimulated (NTS) group. Morphological analysis were performed to evaluate the alterations caused by tactile stimulation, and morphometric analysis were carried out to determine whether the observed changes in optic nerve cytoarchitecture were significantly different between groups and at three different ages (P18, P22, and P32), thereby covering the entire progression of development of the optic nerve from its start to its completion. The rats of both groups presented similar increase in body weight. The morphometric analysis revealed no difference in the astrocyte density between age-matched groups; however, the oligodendrocyte density of TS group was higher compared to the NTS at P22, and P32, but not at P18. The optic nerve of TS group showed an increase of blood vessels and a reduction of damage fiber density when compared to the age-matched pups of NTS. Taken together, these findings support the view that tactile stimulation, an enriching experience, can positively affects the neuroanatomy of the brain, modifying its cellular components by progressive morphological and morphometric changes. PMID:26879768

  5. Bladder and erectile dysfunctions in the Type 2 diabetic Goto-Kakizaki rat.

    PubMed

    Oger-Roussel, Stephanie; Behr-Roussel, Delphine; Caisey, Stephanie; Kergoat, Micheline; Charon, Christine; Audet, Annick; Bernabé, Jacques; Alexandre, Laurent; Giuliano, Francois

    2014-01-15

    Despite the fact that urogenito-sexual complications significantly impact the quality of life of diabetic patients, a robust in vivo experimental model is lacking. Bladder and erectile function in the Type 2 diabetic Goto-Kakizaki (GK) rat and responses to standard-of-care treatments for each disorder have been assessed. GK rats (n = 25, 18-wk-old, GK/Par colony) and age-matched Wistar rats (n = 23), characterized for their metabolic parameters, were used. Bladder function was assessed by cystometry in conscious rats treated by intravenous solifenacin (1 mg/kg). Subsequently, erectile function was assessed under anesthesia following electrical stimulation of the cavernous nerve in presence of intravenous sildenafil (0.3 mg/kg). GK rats displayed detrusor overactivity with a significant increase in frequency/amplitude of nonvoiding contractions during the filling phase, together with an increase in bladder capacity, intercontraction interval, voided volume, and maximal pressure of voiding contraction. Solifenacin significantly decreased parameters characterizing voiding contractions without modifying voiding efficiency. Erectile function in GK rats was markedly impaired and remained so after sildenafil treatment despite a significant improvement. GK rats display both bladder and erectile dysfunctions and respond at least partially to standard-of-care treatments for each disorder, thus representing a suitable model to investigate the pathophysiology and assess the efficacy of new therapeutic agents for Type 2 diabetes-associated bladder and erectile complications. PMID:24305064

  6. Long-term physiological T3 supplementation in hypertensive heart disease in rats.

    PubMed

    Weltman, Nathan Y; Pol, Christine J; Zhang, Youhua; Wang, Yibo; Koder, Adrienne; Raza, Sarah; Zucchi, Riccardo; Saba, Alessandro; Colligiani, Daria; Gerdes, A Martin

    2015-09-15

    Animal studies suggest that hypertension leads to cardiac tissue hypothyroidism, a condition that can by itself lead to heart failure. We have previously shown that short-term thyroid hormone treatment in Spontaneously Hypertensive Heart Failure (SHHF) rats near heart failure is beneficial. This study tested the hypothesis that therapeutic, long-term T3 treatment in SHHF rats can prevent or attenuate cardiac dysfunction. Female SHHF rats were treated orally with a physiological T3 dose (0.04 μg/ml) from 12 to 24 mo of age. Age-matched female SHHF and Wistar-Kyoto rats served as hypertensive and normotensive controls, respectively. SHHF rats had reduced serum free thyroid hormone levels and cardiac tissue T3 levels, LV dysfunction, and elevated LV collagen content compared with normotensive controls. Restoration of serum and cardiac tissue thyroid hormone levels in T3-treated rats was associated with no change in heart rate, but strong trends for improvement in LV systolic function and collagen levels. For instance, end-systolic diameter, fractional shortening, systolic wall stress, and LV collagen levels were no longer significantly different from controls. In conclusion, longstanding hypertension in rats led to chronic low serum and cardiac tissue thyroid hormone levels. Long-term treatment with low-dose T3 was safe. While cardiac dysfunction could not be completely prevented in the absence of antihypertensive treatment, T3 may offer additional benefits as an adjunct therapy with possible improvement in diastolic function. PMID:26254335

  7. Cannabinoids alter endothelial function in the Zucker rat model of type 2 diabetes.

    PubMed

    Stanley, Christopher P; Wheal, Amanda J; Randall, Michael D; O'Sullivan, Saoirse E

    2013-11-15

    Circulating levels of anandamide are increased in diabetes, and cannabidiol ameliorates a number of pathologies associated with diabetes. The aim of the present study was to examine how exposure to anandamide or cannabidiol might affect endothelial dysfunction associated with Zucker Diabetic Fatty rats. Age-matched Zucker Diabetic Fatty and Zucker lean rats were killed by cervical dislocation and their arteries mounted on a myograph at 37 °C. Arteries were incubated for 2h with anandamide, cannabidiol or vehicle, contracted, and cumulative concentration-response curves to acetylcholine were constructed. Anandamide (10 µM, 2h) significantly improved the vasorelaxant responses to acetylcholine in aortae and femoral arteries from Zucker Diabetic Fatty rats but not Zucker lean rats. By contrast, anandamide (1 µM, 2h) significantly blunted acetylcholine-induced vasorelaxation in third-order mesenteric arteries (G3) from Zucker Diabetic Fatty rats. Cannabidiol incubation (10 µM, 2h) improved acetylcholine responses in the arteries of Zucker Diabetic Fatty rats (aorta and femoral) and Zucker lean (aorta, femoral and G3 mesenteric), and this effect was greater in the Zucker Diabetic Fatty rat. These studies suggest that increased circulating endocannabinoids may alter vascular function both positively and negatively in type 2 diabetes, and that part of the beneficial effect of cannabidiol in diabetes may be due to improved endothelium-dependent vasorelaxation. PMID:24120371

  8. Resveratrol Inhibition of Rac1-Derived Reactive Oxygen Species by AMPK Decreases Blood Pressure in a Fructose-Induced Rat Model of Hypertension.

    PubMed

    Cheng, Pei-Wen; Lee, Hui-Chieh; Lu, Pei-Jung; Chen, Hsin-Hung; Lai, Chi-Cheng; Sun, Gwo-Ching; Yeh, Tung-Chen; Hsiao, Michael; Lin, Yu-Te; Liu, Chun-Peng; Tseng, Ching-Jiunn

    2016-01-01

    Recent studies have reported that the activation of AMP-activated protein kinase (AMPK) suppressed oxidative stress. The aim of this study was to examine whether the activation of AMPK in the brain decreased Rac1-induced ROS generation, thereby reducing blood pressure (BP) in rats with fructose-induced hypertension. The inhibition of ROS by treatment with an AMPK activator (oral resveratrol, 10 mg/kg/day) for 1 week decreased the BP and increased the NO production in the rostral ventrolateral medulla (RVLM) of fructose-fed rats but not in control Wistar-Kyoto (WKY) rats. In addition, resveratrol treatment abolished the Rac1-induced increases in the activity of the NADPH oxidase subunits p22-phox and reduced the activity of SOD2, while treatment with an AMPK inhibitor (compound C, 40 μM/day) had the opposite effect, in the fructose-fed rats. Interestingly, the activation of AMPK abolished Rac1 activation and decreased BP by inducing the activities of extracellular signal-regulated kinases 1 and 2 (ERK1/2) and ribosomal protein S6 kinase (RSK) and nNOS phosphorylation in the fructose-fed rats. We conclude that the activation of AMPK decreased BP, abolished ROS generation, and enhanced ERK1/2-RSK-nNOS pathway activity by negatively regulating Racl-induced NADPH oxidase levels in the RVLM during oxidative stress-associated hypertension. PMID:27138844

  9. Resveratrol Inhibition of Rac1-Derived Reactive Oxygen Species by AMPK Decreases Blood Pressure in a Fructose-Induced Rat Model of Hypertension

    PubMed Central

    Cheng, Pei-Wen; Lee, Hui-Chieh; Lu, Pei-Jung; Chen, Hsin-Hung; Lai, Chi-Cheng; Sun, Gwo-Ching; Yeh, Tung-Chen; Hsiao, Michael; Lin, Yu-Te; Liu, Chun-Peng; Tseng, Ching-Jiunn

    2016-01-01

    Recent studies have reported that the activation of AMP-activated protein kinase (AMPK) suppressed oxidative stress. The aim of this study was to examine whether the activation of AMPK in the brain decreased Rac1-induced ROS generation, thereby reducing blood pressure (BP) in rats with fructose-induced hypertension. The inhibition of ROS by treatment with an AMPK activator (oral resveratrol, 10 mg/kg/day) for 1 week decreased the BP and increased the NO production in the rostral ventrolateral medulla (RVLM) of fructose-fed rats but not in control Wistar-Kyoto (WKY) rats. In addition, resveratrol treatment abolished the Rac1-induced increases in the activity of the NADPH oxidase subunits p22-phox and reduced the activity of SOD2, while treatment with an AMPK inhibitor (compound C, 40 μM/day) had the opposite effect, in the fructose-fed rats. Interestingly, the activation of AMPK abolished Rac1 activation and decreased BP by inducing the activities of extracellular signal-regulated kinases 1 and 2 (ERK1/2) and ribosomal protein S6 kinase (RSK) and nNOS phosphorylation in the fructose-fed rats. We conclude that the activation of AMPK decreased BP, abolished ROS generation, and enhanced ERK1/2-RSK-nNOS pathway activity by negatively regulating Racl-induced NADPH oxidase levels in the RVLM during oxidative stress–associated hypertension. PMID:27138844

  10. Detraining reverses exercise-induced improvement in blood pressure associated with decrements of oxidative stress in various tissues in spontaneously hypertensive rats.

    PubMed

    Kilic-Erkek, Ozgen; Kilic-Toprak, Emine; Caliskan, Sadettin; Ekbic, Yusuf; Akbudak, Ismail Hakki; Kucukatay, Vural; Bor-Kucukatay, Melek

    2016-01-01

    This study aimed to investigate the effects of moderate intensity swimming exercise (10 weeks) followed by detraining (for five and 10 weeks) on oxidative stress levels of heart, lung, kidney, and liver tissues and systolic blood pressure (SBP) of spontaneously hypertensive rats (SHR). SHR and control rats were randomized into sedentary, exercised, detrained (5 weeks) and late-detrained (10 weeks) groups. Corresponding sedentary rats were grouped as time 1-2-3. Exercise of 60 min, 5 days/week/10 weeks was applied. Detraining rats underwent the same training protocol and then discontinued training during next 5, 10 weeks. SBP was measured by tail-cuff method. Tissue total oxidant/antioxidant status was measured using a commercial kit and oxidative stress index (OSI) was calculated. Exercise training slightly decreased tissue OSI of SHR and reduced SBP of both groups. Tissue OSI of SHR were higher than WKY and aging resulted in increment of oxidants in groups. detraining yielded time-dependent increments in oxidative stress of all tissues and SBP of both rat groups. Although short-term cessations may be tolerated, our results emphasize the importance of exercising as a way of life for cardiovascular well-being in hypertensives or in individuals who are genetically under risk of hypertension. PMID:26708216

  11. Resting Glutamate Levels and Rapid Glutamate Transients in the Prefrontal Cortex of the Flinders Sensitive Line Rat: A Genetic Rodent Model of Depression

    PubMed Central

    Hascup, Kevin N; Hascup, Erin R; Stephens, Michelle L; Glaser, Paul EA; Yoshitake, Takashi; Mathé, Aleksander A; Gerhardt, Greg A; Kehr, Jan

    2011-01-01

    Despite the numerous drugs targeting biogenic amines for major depressive disorder (depression), the search for novel therapeutics continues because of their poor response rates (∼30%) and slow onset of action (2–4 weeks). To better understand role of glutamate in depression, we used an enzyme-based microelectrode array (MEA) that was selective for glutamate measures with fast temporal (2 Hz) and high spatial (15 × 333 μm) resolution. These MEAs were chronically implanted into the prefrontal cortex of 3- to 6-month-old and 12- to 15-month-old Flinders Sensitive Line (FSL) and control Flinders Resistant Line (FRL) rats, a validated genetic rodent model of depression. Although no changes in glutamate dynamics were observed between 3 and 6 months FRL and FSL rats, a significant increase in resting glutamate levels was observed in the 12- to 15-month-old FSL rats compared with the 3- to 6-month-old FSL and age-matched FRL rats on days 3–5 post-implantation. Our MEA also recorded, for the first time, a unique phenomenon in all the four rat groups of fluctuations in resting glutamate, which we have termed glutamate transients. Although these events lasted only for seconds, they did occur throughout the testing paradigm. The average concentration of these glutamate-burst events was significantly increased in the 12- to 15-month-old FSL rats compared with 3- to 6-month-old FSL and age-matched FRL rats. These studies lay the foundation for future studies of both tonic and phasic glutamate signaling in rat models of depression to better understand the potential role of glutamate signaling in depression. PMID:21525860

  12. Intermittent hypoxia maintains glycemia in streptozotocin-induced diabetic rats.

    PubMed

    Chen, Xiaofei; Zhao, Tong; Huang, Xin; Wu, Liying; Wu, Kuiwu; Fan, Ming; Zhu, Lingling

    2016-05-01

    Increasing studies have shown protective effects of intermittent hypoxia on brain injury and heart ischemia. However, the effect of intermittent hypoxia on blood glucose metabolism, especially in diabetic conditions, is rarely observed. The aim of this study was to investigate whether intermittent hypoxia influences blood glucose metabolism in type 1 diabetic rats. Streptozotocin-induced diabetic adult rats and age-matched control rats were treated with intermittent hypoxia (at an altitude of 3 km, 4 h per day for 3 weeks) or normoxia as control. Fasting blood glucose, body weight, plasma fructosamine, plasma insulin, homeostasis model assessment of insulin resistance (HOMA-IR), pancreas β-cell mass, and hepatic and soleus glycogen were measured. Compared with diabetic rats before treatment, the level of fasting blood glucose in diabetic rats after normoxic treatment was increased (19.88 ± 5.69 mmol/L vs. 14.79 ± 5.84 mmol/L, p < 0.05), while it was not different in diabetic rats after hypoxic treatment (13.14 ± 5.77 mmol/L vs. 14.79 ± 5.84 mmol/L, p > 0.05). Meanwhile, fasting blood glucose in diabetic rats after hypoxic treatment was also lower than that in diabetic rats after normoxic treatment (13.14 ± 5.77 mmol/L vs. 19.88 ± 5.69 mmol/L, p<0.05). Plasma fructosamine in diabetic rats receiving intermittent hypoxia was significantly lower than that in diabetic rats receiving normoxia (1.28 ± 0.11 vs. 1.39 ± 0.11, p < 0.05), while there were no significant changes in body weight, plasma insulin and β-cell mass. HOMA-IR in diabetic rats after hypoxic treatment was also lower compared with diabetic rats after normoxic treatment (3.48 ± 0.48 vs. 3.86 ± 0.42, p < 0.05). Moreover, intermittent hypoxia showed effect on the increase of soleus glycogen but not hepatic glycogen. We conclude that intermittent hypoxia maintains glycemia in streptozotocin-induced diabetic rats and its regulation on muscular

  13. Hydrogen sulfide accelerates wound healing in diabetic rats

    PubMed Central

    Wang, Guoguang; Li, Wei; Chen, Qingying; Jiang, Yuxin; Lu, Xiaohua; Zhao, Xue

    2015-01-01

    Aim: The aim of this study was to explore the role of hydrogen sulfide on wound healing in diabetic rats. Methods: Experimental diabetes in rats was induced by intraperitoneal injection of streptozotocin (STZ) (in 0.1 mol/L citrate buffer, Ph 4.5) at dose of 70 mg/kg. Diabetic and age-matched non-diabetic rats were randomly assigned to three groups: untreated diabetic controls (UDC), treated diabetic administrations (TDA), and non-diabetic controls (NDC). Wound Healing Model was prepared by making a round incision (2.0 cm in diameter) in full thickness. Rats from TDA receive 2% sodium bisulfide ointment on wound, and animals from UDC and NDC receive control cream. After treatment of 21 days with sodium bisulfide, blood samples were collected for determination of vascular endothelial growth factor (VEGF), intercellular cell adhesion molecule-1 (ICAM-1), antioxidant effects. Granulation tissues from the wound were processed for histological examination and analysis of western blot. Results: The study indicated a significant increase in levels of VEGF and ICAM-1 and a decline in activity of coagulation in diabetic rats treated with sodium bisulfide. Sodium bisulfide treatment raised the activity of superoxide dismutase (SOD) and heme oxygenase-1 (HO-1) protein expression, and decreased tumor necrosis factor α (TNF-α) protein expression in diabetic rats. Conclusions: The findings in present study suggested that hydrogen sulfide accelerates the wound healing in rats with diabetes. The beneficial effect of H2S may be associated with formation of granulation, anti-inflammation, antioxidant, and the increased level of vascular endothelial growth factor (VEGF). PMID:26191204

  14. Differential response to chloroethylclonidine in blood vessels of normotensive and spontaneously hypertensive rats: role of α1D- and α1A-adrenoceptors in contraction

    PubMed Central

    Ibarra, Maximiliano; Pardo, J Pablo; López-Guerrero, J Javier; Villalobos-Molina, Rafael

    2000-01-01

    The effects of chloroethylclonidine on α1-adrenoceptor-mediated contraction in endothelium-denuded caudal arteries and aorta from normotensive Wistar and Wistar Kyoto (WKY), and from spontaneously hypertensive (SHR) rats were evaluated. Chloroethylclonidine elicited concentration-dependent contractions. Maximal contraction was similar in caudal arteries among strains (≈40% of noradrenaline effect). However, chloroethylclonidine elicited a higher contraction in aorta from SHR than from normotensive rats. In Wistar aorta chloroethylclonidine produced the smallest contractile response. In SHR aorta, BMY 7378 and 5-methylurapidil blocked chloroethylclonidine-elicited contraction, while (+)-cyclazocine did not inhibit it; while in caudal arteries, 5-methylurapidil blocked chloroethylclonidine action; the other antagonists had no effect. In chloroethylclonidine-treated aorta noradrenaline elicited biphasic contraction-response curves, indicating a high affinity (pD2, 8.5–7.5) chloroethylclonidine-sensitive component and a low affinity (pD2, 6.3–5.2) chloroethylclonidine-insensitive component. The high affinity component was blocked by chloroethylclonidine; while in caudal arteries noradrenaline elicited monophasic contraction-response curves with pD2 values (6.5–5.7) similar to the low affinity component in aorta. Chloroethylclonidine inhibition of noradrenaline response was greater in aorta than in caudal arteries. Chloroethylclonidine increased the EC50 values of noradrenaline ≈1000 fold in aorta and ≈10 fold in caudal arteries. In SHR aorta BMY 7378 protected α1D-adrenoceptors and in caudal arteries 5-methylurapidil protected α1A-adrenoceptors from chloroethylclonidine alkylation, allowing noradrenaline to elicit contraction. These results show marked strain-dependent differences in the ability of chloroethylclonidine to contract aorta; moreover, chloroethylclonidine stimulates α1D-adrenoceptors in aorta and α1A-adrenoceptors in caudal arteries. The

  15. Adrenoreceptor development in rat cerebrum and the effects of ionizing radiation

    SciTech Connect

    Nyquist-Battie, C.; Fortney, R.; Gochee, A.

    1984-01-01

    Previous studies in the rat have shown that neonatal radiation alters certain aspects of CNS monoaminergic systems including altering cerebral norepinephrine levels (17). To determine if cerebral adrenoreceptor development is also altered by neonatal ionizing radiation, a single dose of whole body gamma-radiation was administered to rats on postnatal day two. This treatment did not alter (/sup 3/H)-dihydroalprenolol (beta adrenoreceptor) or (/sup 3/H)-WB4101 (alpha1 adrenoreceptor) binding when cerebra from irradiated animals were compared to age-matched sham-irradiated controls on postnatal days 9, 15 and 35. In contrast, (/sup 3/H)-yohimbine (alpha2-adrenoreceptor) binding was altered in gamma-irradiation, a change manifested on postnatal days 9, 15 and 35 by lower than normal receptor densities (pmoles/g wet weight of tissue) although no radiation-induced changes in K/sub D/ were apparent.

  16. Muscarinic receptor plasticity in the brain of senescent rats: down-regulation after repeated administration of diisopropyl fluorophosphate

    SciTech Connect

    Pintor, A.; Fortuna, S.; Volpe, M.T.; Michalek, H.

    1988-01-01

    Potential age-related differences in the response of Fischer 344 rats to subchronic treatment with diisopropylfluorophosphate (DFP) were evaluated in terms of brain cholinesterase (ChE) inhibition and muscarinic receptor sites. Male 3- and 24-month old rats were sc injected with sublethal doses of DFP for 2 weeks and killed 48 hrs after the last treatment. In the cerebral cortex, hippocampus and striatum of control rats a significant age-related reduction of ChE and of maximum number of /sup 3/H-QNB binding sites (Bmax) was observed. The administration of DFP to senescent rats resulted in more pronounced and longer lasting syndrome of cholinergic stimulation, with marked body weight loss and 60% mortality. The percentage inhibition of brain ChE induced by DFP did not differ between young and senescent rats. As expected, in young rats DFP caused a significant decrease of Bmax, which in the cerebral cortex reached about 40%. In the surviving senescent rats, the percentage decrease of Bmax due to DFP with respect to age-matched controls was very similar to that of young animals, especially in the cerebral cortex. Thus there is great variability in the response of aged rats to DFP treatment, from total failure of adaptive mechanisms resulting in death to considerable muscarinic receptor plasticity.

  17. Early development of intracellular calcium cycling defects in intact hearts of spontaneously hypertensive rats

    PubMed Central

    Kapur, Sunil; Aistrup, Gary L.; Sharma, Rohan; Kelly, James E.; Arora, Rishi; Zheng, Jiabo; Veramasuneni, Mitra; Kadish, Alan H.; Balke, C. William

    2010-01-01

    Defects in excitation-contraction coupling have been reported in failing hearts, but little is known about the relationship between these defects and the development of heart failure (HF). We compared the early changes in intracellular Ca2+ cycling to those that underlie overt pump dysfunction and arrhythmogenesis found later in HF. Laser-scanning confocal microscopy was used to measure Ca2+ transients in myocytes of intact hearts in Wistar-Kyoto (WKY) rats and spontaneously hypertensive rats (SHRs) at different ages. Early compensatory mechanisms include a positive inotropic effect in SHRs at 7.5–9 mo compared with 6 mo. Ca2+ transient duration increased at 9 mo in SHRs, indicating changes in Ca2+ reuptake during decompensation. Cell-to-cell variability in Ca2+ transient duration increased at 7.5 mo, decreased at 9 mo, and increased again at 22 mo (overt HF), indicating extensive intercellular variability in Ca2+ transient kinetics during disease progression. Vulnerability to intercellular concordant Ca2+ alternans increased at 9–22 mo in SHRs and was mirrored by a slowing in Ca2+ transient restitution, suggesting that repolarization alternans and the resulting repolarization gradients might promote reentrant arrhythmias early in disease development. Intercellular discordant and subcellular Ca2+ alternans increased as early as 7.5 mo in SHRs and may also promote arrhythmias during the compensated phase. The incidence of spontaneous and triggered Ca2+ waves was increased in SHRs at all ages, suggesting a higher likelihood of triggered arrhythmias in SHRs compared with WKY rats well before HF develops. Thus serious and progressive defects in Ca2+ cycling develop in SHRs long before symptoms of HF occur. Defective Ca2+ cycling develops early and affects a small number of myocytes, and this number grows with age and causes the transition from asymptomatic to overt HF. These defects may also underlie the progressive susceptibility to Ca2+ alternans and Ca2+ wave

  18. [Studies on the iodide metabolism and the expression of thyroglobulin and thyroid peroxidase mRNA in the thyroid of BB/W rats].

    PubMed

    Fukasawa, N

    1991-10-20

    BioBreeding/Worcester (BB/W) rats develop insulin dependent diabetes mellitus (IDDM) and lymphocytic thyroiditis (LT) spontaneously. Our previous studies have shown that BB/W (Saitama-Tokyo colony) rats develop LT at about 10 weeks of age. Their serum TSH values increase as LT extends, although their serum thyroid hormone levels remain normal. This indicates that BB/W rats suffer from subclinical hypothyroidism. To investigate whether BB/W rats have a defect in iodide metabolism, the thyroidal radioactive iodine uptake (RAIU) in BB/W rats was examined. Thyroidal RAIU at 3hr in both 8 and 16 week-old BB/W rats was significantly higher than that in age-matched normal Wistar rats. On the other hand, BB/W rats had significantly lower 48hr thyroidal RAIU than normal Wistar rats. This suggests that BB/W rats appear to have some defects in iodide metabolism, especially in iodide organification even before the development of LT. The expression of thyroid peroxidase (TPO) and thyroglobulin (Tg) mRNA in BB/W and Wistar rats was then examined using the Northern blot analysis. The expression of both TPO and Tg mRNA was greatly decreased in BB/W rats compared with that in Wistar rats despite the high serum TSH levels in BB/W rats. This indicates that BB/W rats may have pretranslational defects in TPO and Tg synthesis, resulting in the impaired thyroid hormone synthesis. In the present study, it has been demonstrated that BB/W rats appear to have a defect(s) in iodide metabolism possibly due to some abnormalities in TPO and Tg synthesis. PMID:1752338

  19. Progesterone Treatment Shows Benefit in Female Rats in a Pediatric Model of Controlled Cortical Impact Injury

    PubMed Central

    Geddes, Rastafa I.; Peterson, Bethany L.; Stein, Donald G.; Sayeed, Iqbal

    2016-01-01

    Purpose We recently showed that progesterone treatment can reduce lesion size and behavioral deficits after moderate-to-severe bilateral injury to the medial prefrontal cortex in immature male rats. Whether there are important sex differences in response to injury and progesterone treatment in very young subjects has not been given sufficient attention. Here we investigated progesterone’s effects in the same model of brain injury but with pre-pubescent females. Methods Twenty-eight-day-old female Sprague-Dawley rats received sham (n = 14) or controlled cortical impact (CCI) (n = 21) injury, were given progesterone (8 mg/kg body weight) or vehicle injections on post-injury days (PID) 1–7, and underwent behavioral testing from PID 9–27. Brains were evaluated for lesion size at PID 28. Results Lesion size in vehicle-treated female rats with CCI injury was smaller than that previously reported for similarly treated age-matched male rats. Treatment with progesterone reduced the effect of CCI on extent of damage and behavioral deficits. Conclusion Pre-pubescent female rats with midline CCI injury to the frontal cortex have reduced morphological and functional deficits following progesterone treatment. While gender differences in susceptibility to this injury were observed, progesterone treatment produced beneficial effects in young rats of both sexes following CCI. PMID:26799561

  20. Farnesoid X receptor agonist CDCA reduces blood pressure and regulates vascular tone in spontaneously hypertensive rats.

    PubMed

    Li, Chenyu; Li, Jing; Weng, Xu; Lan, Xiaofang; Chi, Xiangbo

    2015-07-01

    The Farnesoid X receptor (FXR) is a member of the nuclear receptor superfamily, which plays an essential role in lipid homeostasis and glucose metabolism. However, whether or not FXR can prevent rise in blood pressure remains unknown. Here, we investigate the possibility of using chenodeoxycholic acid (CDCA), a natural ligand of FXR, to attenuate elevated blood pressure in spontaneously hypertensive rats (SHR). SHR and Wistar-Kyoto rats (WKY) were treated with CDCA (30 mg/kg) for 8 weeks. Compared with vehicle control, CDCA attenuated rise in blood pressure in SHR. In addition, CDCA improved vasorelaxation and diminished the contractile response to endothelin-1 (ET-1) in mesenteric arteries from SHR. CDCA also stimulated endothelial nitric oxide synthase (eNOS) expression, repressed ET-1 levels, and inhibited NF-κB activities in mesenteric arteries of the SHR. Overall, we showed that CDCA treatment reduces systolic blood pressure, improves vascular relaxation, and inhibits vasoconstriction activity in SHR. The repressed ET-1 level, the raised eNOS expression, and the ameliorated inflammation in mesenteric arteries could be responsible for the vasorelaxant and hypotensive effect of CDCA. These findings support a potential role for FXR as a regulator in vascular activities and in the development of treatment for hypertension. PMID:26188398

  1. Evidence for reduced cancellous bone mass in the spontaneously hypertensive rat

    NASA Technical Reports Server (NTRS)

    Wang, T. M.; Hsu, J. F.; Jee, W. S.; Matthews, J. L.

    1993-01-01

    The histomorphometric changes in the proximal tibial metaphysis and epiphyseal growth plate and midtibial shaft of 26-week-old spontaneously hypertensive rats (SHR) compared with those of the corresponding normotensive Wistar-Kyoto (WKY) rats were studied. A decrease in body weight, growth plate thickness, and longitudinal growth rate of the proximal tibial epiphysis, trabecular bone volume, trabecular thickness and number, the number of osteoblasts and osteoprogenitor cells per millimeter square surface of the proximal tibial metaphysis, periosteal and endocortical apposition rate and bone formation rate of the tibial diaphysis were observed in the SHR. Additionally, systolic blood pressure, the number of osteoclasts per millimeter square surface and average number of nuclei per osteoclast of the proximal tibial metaphysis were significantly increased. Thus, osteoclastic activity is dominant over osteoblastic and chondroblastic activity in the SHR that results in a cancellous bone deficit in the skeleton. It will require additional work to ascertain the underlying cause for this condition as several factors in the SHR with a potential for causing this change are present, including elevated parathyroid hormone (PTH), depressed 1,25-(OH)2D3, low calcium absorption, reduced body weight (reduced loading) elevated blood pressure and possibly other direct cell differences in the mutant strain. At present elevated PTH and adaptation to underloading from reduced weight are postulated to be a likely cause, but additional studies are required to test this interpretation.

  2. AB096. Taurine supplementation improves erectile function in rats with streptozotocin-induced type 1 diabetes via amelioration of penile fibrosis and endothelial dysfunction

    PubMed Central

    Ruan, Yajun; Li, Mingchao; Wang, Tao; Yang, Jun; Rao, Ke; Wang, Shaogang; Yang, Weimin; Liu, Jihong; Ye, Zhangqun

    2016-01-01

    Objective For patients with diabetes, erectile dysfunction (ED) is common and greatly affects quality of life. However, these patients often exhibit a poor response to first-line oral phosphodiesterase type 5 inhibitors. The aim of this study was to investigate whether taurine, a sulfur-containing amino acid, affects diabetic ED (DED). Methods Type 1 diabetes mellitus was induced in male rats using streptozotocin. After 12 weeks, an apomorphine test was conducted to confirm DED. Only rats with DED were administered taurine or vehicle for four weeks. Age-matched nondiabetic rats were administered saline intraperitoneally for four weeks. Erectile function was evaluated by electrical stimulation of the cavernous nerve. Histologic and molecular alterations of the corpus cavernosum also were analyzed. Results Erectile function was significantly reduced in the diabetic rats compared with in the nondiabetic rats, and was ameliorated in the diabetic rats treated with taurine. The corpus cavernosum of the rats with DED exhibited severe fibrosis and decreased smooth muscle content. Deposition of extracellular matrix proteins was increased in the diabetic rats, while expression of endothelial nitric oxide synthase/cyclic guanosine monophosphate/nitric oxide pathway–related proteins was reduced. Taurine supplementation restored erectile response as well as histologic and molecular alterations. Conclusions Taurine supplementation improves erectile function in rats with DED probably by potential antifibrotic activity. This finding provides evidence for a potential new therapy for DED.

  3. Effects of Triclocarban on Intact Immature Male Rat

    PubMed Central

    Duleba, Antoni J.; Ahmed, Mohamed I.; Sun, Meng; Gao, Allen C.; Villanueva, Jesus; Conley, Alan J.; Turgeon, Judith L.; Benirschke, Kurt; Gee, Nancy A.; Chen, Jiangang; Green, Peter G.; Lasley, Bill L.

    2011-01-01

    Triclocarban (TCC; 3,4,4′-trichlorocarbanilide) is an antimicrobial agent used widely in various personal hygiene products including soaps. Recently, TCC has been shown to enhance testosterone-induced effects in vitro and to enlarge accessory sex organs in castrated male rats. This study was designed to evaluate the effects of TCC on intact age-matched male rats and on human prostate LNCaP and C4–2B cells. Seven-week-old male Sprague-Dawley rats received either a normal diet or a diet supplemented with TCC (0.25% in diet) for 10 days. Triclocarban induced hyperplasia of accessory sex organs in the absence of significant qualitative histological changes. Serum luteinizing hormone (LH) and testosterone were not significantly altered by TCC treatment. In prostate cancer-derived LNCaP and C4–2B cells, TCC potentiated androgen actions via androgen receptor-dependent actions. In conclusion, TCC significantly affects intact male reproductive organs and potentiates androgen effects in prostate cancer cells. PMID:20889956

  4. Effects of spaceflight on rat humerus geometry, biomechanics, and biochemistry

    NASA Technical Reports Server (NTRS)

    Vailas, A. C.; Zernicke, R. F.; Grindeland, R. E.; Kaplansky, A.; Durnova, G. N.; Li, K. C.; Martinez, D. A.

    1990-01-01

    The effects of a 12.5-day spaceflight (Cosmos 1887 biosatellite) on the geometric, biomechanical, and biochemical characteristics of humeri of male specific pathogen-free rats were examined. Humeri of age-matched basal control, synchronous control, and vivarium control rats were contrasted with the flight bones to examine the influence of growth and space environment on bone development. Lack of humerus longitudinal growth occurred during the 12.5 days in spaceflight. In addition, the normal mid-diaphysial periosteal appositional growth was affected; compared with their controls, the spaceflight humeri had less cortical cross-sectional area, smaller periosteal circumferences, smaller anterior-posterior periosteal diameters, and smaller second moments of area with respect to the bending and nonbending axes. The flexural rigidity of the flight humeri was comparable to that of the younger basal control rats and significantly less than that of the synchronous and vivarium controls; the elastic moduli of all four groups, nonetheless, were not significantly different. Generally, the matrix biochemistry of the mid-diaphysial cross sections showed no differences among groups. Thus, the spaceflight differences in humeral mechanical strength and flexural rigidity were probably a result of the differences in humeral geometry rather than material properties.

  5. Beta-adrenoceptor-mediated vasodilation of retinal blood vessels is reduced in streptozotocin-induced diabetic rats.

    PubMed

    Nakazawa, Taisuke; Sato, Ayumi; Mori, Asami; Saito, Maki; Sakamoto, Kenji; Nakahara, Tsutomu; Ishii, Kunio

    2008-01-01

    We investigated the effects of epinephrine and dopamine on retinal blood vessels in streptozotocin (STZ, 80 mg/kg, i.p.)-treated rats and age-matched control rats to determine whether diabetes mellitus alters the retinal vascular responses to circulating catecholamines. Experiments were performed 6-8 weeks after treatment with STZ or the vehicle. The fundus images were captured with the digital fundus camera system for small animals we developed and diameters of retinal blood vessels contained in the digital images were measured. Epinephrine increased the diameters of retinal blood vessels, but the vasodilator responses were reduced in diabetic rats. Dopamine produced a biphasic retinal vascular response with an initial vasoconstriction followed by a vasodilation. The vasoconstrictor effects of dopamine on retinal arterioles were enhanced in diabetic rats, whereas the difference between the two groups was abolished by treatment with propranolol. The vasodilator effect of isoproterenol, but not of the activator of adenylyl cyclase colforsin, on retinal blood vessels was reduced in diabetic rats. No difference in vasoconstriction of retinal blood vessels to phenylephrine between non-diabetic and diabetic rats was observed. The vasodilator responses of retinal blood vessels to 1,1-dimethyl-4-phenylpiperazinium, a ganglionic nicotinic receptor agonist, were also attenuated in diabetic rats. These results suggest that diabetes mellitus alters the retinal vascular responses to circulating catecholamines and the impairment of vasodilator responses mediated by beta-adrenoceptors contributes to the alteration. PMID:18585480

  6. Role of hepatic blood flow and metabolism in the pharmacokinetics of ten drugs in lean, aged and obese rats.

    PubMed

    Subramanian, Murali; Kurawattimath, Vishwanath; Pocha, Krishna; Freeden, Chris; Rao, Indranil; Mariappan, T Thanga; Marathe, Punit H; Vikramadithyan, Reeba K; Abraham, Pamela; Kulkarni, Chetan P; Katnapally, Prasanna; Nutakki, Ravikumar; Paruchury, Sundeep; Bhutani, Priyadeep; Mandlekar, Sandhya

    2014-12-01

    1. The effect of age and obesity on the pharmacokinetics (PK), hepatic blood flow (HBF) and liver metabolism of 10 compounds was determined in rats. The animals fed a high-fat diet were defined as the diet-induced obese (DIO) group, while the animals that were aged similar to the DIO rats but not fed with high-fat diet were called the age-matched (AM) group. 2. The clearance (CL) values of high CL compounds (CL > 50 mL/min/kg, namely propranolol, diazepam, phenytoin, ethinylestradiol, lorcaserin and fenfluramine) decreased significantly (1.5- to 6-fold) in DIO and AM rats as compared to lean rats, while there was no clear trend for change in CL for the low-to-moderate CL compounds (CL < 50 mL/min/kg, namely atenolol, chlorzoxazone, vancomycin and sibutramine). Hepatocytes incubations revealed a change in half life (t1/2) only for phenytoin. The body weight normalized liver weights and HBF of AM and DIO rats were found to be 2- to 3-fold lower than in lean rats. 3. Our findings suggest that age, and diet to a lesser extent, can reduce HBF and body normalized liver weights and, hence, also reduce CL values for high CL compounds in rats. PMID:24947446

  7. Behavioral changes following PCB 153 exposure in the Spontaneously Hypertensive rat – an animal model of Attention-Deficit/Hyperactivity disorder

    PubMed Central

    2014-01-01

    Background Attention-Deficit/Hyperactivity Disorder (ADHD) is a behavioral disorder affecting 3-5% of children. Although ADHD is highly heritable, environmental factors like exposure during early development to various toxic substances like polychlorinated biphenyls (PCBs) may contribute to the prevalence. PCBs are a group of chemical industrial compounds with adverse effects on neurobiological and cognitive functioning, and may produce behavioral impairments that share significant similarities with ADHD. The present study examined the relation between exposure to PCB 153 and changes in ADHD-like behavior in an animal model of ADHD, the spontaneously hypertensive rats (SHR/NCrl), and in Wistar Kyoto (WKY/NHsd) controls. Methods SHR/NCrl and WKY/NHsd, males and females, were orally given PCB 153 dissolved in corn oil at around postnatal day (PND) 8, 14, and 20 at a dosage of 1, 3 or 6 mg/kg bodyweight at each exposure. The control groups were orally administered corn oil only. The animals were behaviorally tested for exposure effects from PND 37 to 64 using an operant procedure. Results Exposure to PCB 153 was associated with pronounced and long-lasting behavioral changes in SHR/NCrl. Exposure effects in the SHR/NCrl depended on dose, where 1 mg/kg tended to reduce ADHD-like behaviors and produce opposite behavioral effects compared to 3 mg/kg and 6 mg/kg, especially in the females. In the WKY/NHsd controls and for the three doses tested, PCB 153 exposure produced a few specific behavioral changes only in males. The data suggest that PCB 153 exposure interacts with strain and sex, and also indicate a non-linear dose–response relation for the behaviors observed. Conclusions Exposure to PCB 153 seems to interact with several variables including strain, sex, dose, and time of testing. To the extent that the present findings can be generalized to humans, exposure effects of PCB 153 on ADHD behavior depends on amount of exposure, where high doses may aggravate ADHD

  8. Repeated neonatal propofol administration induces sex-dependent long-term impairments on spatial and recognition memory in rats.

    PubMed

    Gonzales, Edson Luck T; Yang, Sung Min; Choi, Chang Soon; Mabunga, Darine Froy N; Kim, Hee Jin; Cheong, Jae Hoon; Ryu, Jong Hoon; Koo, Bon-Nyeo; Shin, Chan Young

    2015-05-01

    Propofol is an anesthetic agent that gained wide use because of its fast induction of anesthesia and rapid recovery post-anesthesia. However, previous studies have reported immediate neurodegeneration and long-term impairment in spatial learning and memory from repeated neonatal propofol administration in animals. Yet, none of those studies has explored the sex-specific long-term physical changes and behavioral alterations such as social (sociability and social preference), emotional (anxiety), and other cognitive functions (spatial working, recognition, and avoidance memory) after neonatal propofol treatment. Seven-day-old Wistar-Kyoto (WKY) rats underwent repeated daily intraperitoneal injections of propofol or normal saline for 7 days. Starting fourth week of age and onwards, rats were subjected to behavior tests including open-field, elevated-plus-maze, Y-maze, 3-chamber social interaction, novel-object-recognition, passive-avoidance, and rotarod. Rats were sacrificed at 9 weeks and hippocampal protein expressions were analyzed by Western blot. Results revealed long-term body weight gain alterations in the growing rats and sex-specific impairments in spatial (female) and recognition (male) learning and memory paradigms. A markedly decreased expression of hippocampal NMDA receptor GluN1 subunit in female- and increased expression of AMPA GluR1 subunit protein expression in male rats were also found. Other aspects of behaviors such as locomotor activity and coordination, anxiety, sociability, social preference and avoidance learning and memory were not generally affected. These results suggest that neonatal repeated propofol administration disrupts normal growth and some aspects of neurodevelopment in rats in a sex-specific manner. PMID:25995824

  9. Repeated Neonatal Propofol Administration Induces Sex-Dependent Long-Term Impairments on Spatial and Recognition Memory in Rats

    PubMed Central

    Gonzales, Edson Luck T.; Yang, Sung Min; Choi, Chang Soon; Mabunga, Darine Froy N.; Kim, Hee Jin; Cheong, Jae Hoon; Ryu, Jong Hoon; Koo, Bon-Nyeo; Shin, Chan Young

    2015-01-01

    Propofol is an anesthetic agent that gained wide use because of its fast induction of anesthesia and rapid recovery post-anesthesia. However, previous studies have reported immediate neurodegeneration and long-term impairment in spatial learning and memory from repeated neonatal propofol administration in animals. Yet, none of those studies has explored the sex-specific long-term physical changes and behavioral alterations such as social (sociability and social preference), emotional (anxiety), and other cognitive functions (spatial working, recognition, and avoidance memory) after neonatal propofol treatment. Seven-day-old Wistar-Kyoto (WKY) rats underwent repeated daily intraperitoneal injections of propofol or normal saline for 7 days. Starting fourth week of age and onwards, rats were subjected to behavior tests including open-field, elevated-plus-maze, Y-maze, 3-chamber social interaction, novel-object-recognition, passive-avoidance, and rotarod. Rats were sacrificed at 9 weeks and hippocampal protein expressions were analyzed by Western blot. Results revealed long-term body weight gain alterations in the growing rats and sex-specific impairments in spatial (female) and recognition (male) learning and memory paradigms. A markedly decreased expression of hippocampal NMDA receptor GluN1 subunit in female- and increased expression of AMPA GluR1 subunit protein expression in male rats were also found. Other aspects of behaviors such as locomotor activity and coordination, anxiety, sociability, social preference and avoidance learning and memory were not generally affected. These results suggest that neonatal repeated propofol administration disrupts normal growth and some aspects of neurodevelopment in rats in a sex-specific manner. PMID:25995824

  10. Glucose transporter levels in tissues of spontaneously diabetic Zucker fa/fa rat (ZDF/drt) and viable yellow mouse (Avy/a).

    PubMed

    Slieker, L J; Sundell, K L; Heath, W F; Osborne, H E; Bue, J; Manetta, J; Sportsman, J R

    1992-02-01

    We used antibodies to the fat/muscle glucose transporter (GLUT4) and the liver glucose transporter (GLUT2) to measure levels of these proteins in various tissues of two rodent models of non-insulin-dependent (type II) diabetes mellitus: the obese spontaneously diabetic male Zucker fa/fa rat (ZDF/drt) and the male viable yellow Avy/a obese diabetic mouse. The ZDF/drt strain generally develops overt diabetes associated with decreased plasma insulin levels. Depending on the age of the animals, the ZDF/drt rats can be arbitrarily segregated into age-matched obese, mildly diabetic (blood glucose less than 11 mM) and obese, and severely diabetic (blood glucose greater than 20 mM) groups. Avy/a mice are comparably hyperglycemic but unlike the ZDF/drt rats are severely hyperinsulinemic. In both groups of diabetic animals, GLUT4 in adipose tissue, heart, and skeletal muscle was reduced 25-55%, and GLUT2 in liver was increased 30-40%, relative to lean, age-matched controls. However, when the mildly diabetic ZDF/drt rats were compared to the lean controls, the only significant difference was a 25% reduction of GLUT4 in heart. Within all of the ZDF/drt rats (excluding the lean controls), GLUT2 in liver and GLUT4 in adipose tissue, heart, and skeletal muscle correlated significantly with glycemia. These data suggest that, in these two models of type II diabetes, glucose transporter levels in muscle, adipose tissue, and liver are regulated in a tissue-selective manner in response to changes in insulin and glucose. Furthermore, at least in the ZDF/drt rat, alterations in GLUT2 and/or GLUT4 protein levels appear not to be associated with obesity per se but appear to be secondary to the severely diabetic state.(ABSTRACT TRUNCATED AT 250 WORDS) PMID:1733808

  11. HIV-1 Transgenic Rat Prefrontal Cortex Hyper-Excitability is Enhanced by Cocaine Self-Administration.

    PubMed

    Wayman, Wesley N; Chen, Lihua; Hu, Xiu-Ti; Napier, T Celeste

    2016-07-01

    The medial prefrontal cortex (mPFC) is dysregulated in HIV-1-infected humans and the dysregulation is enhanced by cocaine abuse. Understanding mPFC pathophysiology in this comorbid state has been hampered by the dearth of relevant animal models. To help fill this knowledge gap, electrophysiological assessments were made of mPFC pyramidal neurons (PN) from adult male HIV-1 transgenic (Tg) F344 rats (which express seven of the nine HIV-1 toxic proteins) and non-Tg F344 rats that self-administered cocaine for 14 days (COC-SA), as well as saline-yoked controls (SAL-Yoked) and experimentally naive Tg and non-Tg rats. Forebrain slices were harvested and prepared for whole-cell patch-clamp recording, and in treated rats, this occurred after 14-18 days of forced abstinence. Aged-matched rats were used for immunohistochemical detection of the L-channel protein, Cav1.2-α1c. We determined that: (i) the two genotypes acquired the operant task and maintained similar levels of COC-SA, (ii) forced abstinence from COC-SA enhanced mPFC PN excitability in both genotypes, and neurons from Tg rats exhibited the greatest pathophysiology, (iii) neurons from SAL-Yoked Tg rats were more excitable than those from SAL-Yoked non-Tg rats, and in Tg rats (iv) blockade of L-type Ca(2+) channels reduced the enhanced excitability, and (v) Cav1.2-immunoreactivity was increased. These findings provide the first assessment of the mPFC pathophysiology in a rodent model of HIV-1-mediated neuropathology with and without cocaine self-administration. Outcomes reveal an enhanced cortical excitability during chronic exposure to HIV-1 proteins that is excessively exacerbated with cocaine abuse. Such neuropathophysiology may underlie the cognitive dysregulation reported for comorbid humans. PMID:26677947

  12. Insulin binding and glucose uptake of adipocytes in rats adapted to hypergravitational force

    NASA Technical Reports Server (NTRS)

    Kobayashi, M.; Mondon, C. E.; Oyama, J.

    1980-01-01

    Rats were exposed to 4.15 g for 1 yr and weight and age matched, and lean noncentrifuged rats were used as control groups. Rats exposed to chronic hypergravity (hypergravic rats) were found to show lower ambient insulin levels, greater food intake with smaller body weight gain, and decreased size of isolated adipocytes. The ability of adipocytes from the hypergravic rats to bind insulin was increased. With Scatchard analysis, both number and affinity of receptors were increased. In contrast to the increased binding, glucose transport was found to be decreased in adipocytes from these animals. However, when the data were expressed as a percentage of maximal effect, the half maximal insulin effect for both the hypergravic and lean control groups was produced at an insulin concentration of 0.23 + or - 0.02 ng/ml, which was lower than the insulin concentration of 0.31 + or - 0.02 ng/ml for the weight-matched control group (P less than 0.05). This increased insulin sensitivity in the hypergravic group was accounted for by an increased number of receptors.

  13. An Automated Self-similarity Analysis of the Pulmonary Tree of the Sprague-Dawley Rat

    PubMed Central

    Einstein, Daniel R.; Neradilak, Blazej; Pollisar, Nayak; Minard, Kevin R.; Wallis, Chris; Fanucchi, Michelle; Carson, James P.; Kuprat, Andrew P.; Kabilan, Senthil; Jacob, Richard E.; Corley, Richard A.

    2009-01-01

    We present the results of an automated analysis of the morphometry of the pulmonary airway trees of the Sprague Dawley rat. Our work is motivated by a need to inform lower-dimensional mathematical models in order to prescribe realistic boundary conditions for multiscale hybrid models of rat lung mechanics. Silicone casts were made from three age-matched, male Sprague Dawley rats, immersed in a gel containing a contrast agent and subsequently imaged with magnetic resonance (MR). From a segmentation of this data, we extracted a connected graph, representing the airway centerline. Segment statistics (lengths and diameters) were derived from this graph. To validate this MR imaging/digital analysis method, airway segment measurements were compared to nearly one thousand measurements collected by hand using an optical microscope from one of the rat lung casts. To evaluate the reproducibility of the MR imaging/digital analysis method, two lung casts were each imaged three times with randomized orientations in the MR bore. Diameters and lengths of randomly selected airways were compared among each of the repeated imaging datasets to estimate the variability. Finally, we analyzed the morphometry of the airway tree by assembling individual airway segments into structures that span multiple generations, which we call branches. We show that branches not segments are the fundamental repeating unit in the rat lung and develop simple mathematical relationships describing these structures for the entire lung. Our analysis shows that airway diameters and lengths have both a deterministic and stochastic character. PMID:18951511

  14. Brain nitric oxides synthase in major pelvic ganglia of aged (LETO) and diabetic (OLETF) rats.

    PubMed

    Salama, N; Tamura, M; Tsuruo, Y; Ishimura, K; Kagawa, S

    2002-01-01

    This study was conducted to evaluate the effects of aging and diabetes mellitus (DM) on brain nitric oxide synthase (bNOS) expression in major pelvic ganglia (MPG) of rats. Otsuka Long Evans Tokushima Fatty rats (12, 30, and 70 weeks old), which are genetic models with non-insulin-dependent DM (NIDDM), and age-matched nondiabetic Long Evans Tokushima Otsuka controls were used. The MPG of all rats in this study were subjected to cryo-sectioning and staining with bNOS polyclonal AB and rhodamine-conjugated rabbit IgG. Fluorescence intensities of the stained neurons were assessed in randomly selected fields per each specimen. Animals of both groups revealed significant decline in the staining intensity of their neurons with aging and the progress of DM, but diabetic rats showed more decline than controls. In conclusion, both aging and NIDDM could decrease bNOS expression in rat MPG. However, NIDDM has a more evident effect than aging on that expression. The decrease in bNOS may cause a disturbance in functions of the target pelvic structures of these ganglia under both conditions. PMID:12230824

  15. Schwann cell myelination of the myelin deficient rat spinal cord following X-irradiation

    SciTech Connect

    Duncan, I.D.; Hammang, J.P.; Gilmore, S.A.

    1988-01-01

    The myelin-deficient (md) rat is an X-linked myelin mutant that has an abnormality of oligodendrocytes and a severe paucity of myelin throughout the CNS. This lack of myelin makes it an ideal model in which to study the cellular interactions that occur when foreign myelinating cells are induced in the milieu of this nonmyelinated CNS. In this study, Schwann cells were induced in the lumbosacral spinal cord by exposing it to radiation, a technique demonstrated repeatedly in other nonmutant strains of rats. Md rats and their age-matched littermates were irradiated (3,000 to 4,000 R) at 3 days of age and perfused 16-22 days later after pulse labeling with tritiated thymidine. In the md rat, Schwann cell invasion progressed from the area of the spinal cord-nerve root junction and extended into the dorsal columns and adjacent gray matter. Autoradiographic evidence revealed that many of these cells incorporated 3H-thymidine, indicating that they were undergoing proliferation. Ultrastructural observations showed that there was an integration of these intraspinal Schwann cells with the cells normally occurring in this environment, i.e., oligodendrocytes and astrocytes. The extent of migration and division of Schwann cells, as well as their interactions with glial cells, were similar to those seen in the nonmutant irradiated littermates. These studies provide conclusive evidence that md rat axons are normal with respect to their ability to provide trophic and mitogenic signals to myelinating cells.

  16. Functional MRI and neural responses in a rat model of Alzheimer’s disease

    PubMed Central

    Sanganahalli, Basavaraju G.; Herman, Peter; Behar, Kevin L.; Blumenfeld, Hal; Rothman, Douglas L.; Hyder, Fahmeed

    2013-01-01

    Based on the hypothesis that brain plaques and tangles can affect cortical functions in Alzheimer's disease (AD) and thus modify functional activity, we investigated functional responses in an AD rat model (called the Samaritan Alzheimer’s rat achieved by ventricular infusion of amyloid peptide) and age-matched healthy control. High-field functional magnetic resonance imaging (fMRI) and extracellular neural activity measurements were applied to characterize sensory-evoked responses. Electrical stimulation of the forepaw led to BOLD and neural responses in the contralateral somatosensory cortex and thalamus. In AD brain we noted much smaller BOLD activation patterns in the somatosensory cortex (i.e., about 50% less activated voxels compared to normal brain). While magnitudes of BOLD and neural responses in the cerebral cortex were markedly attenuated in AD rats compared to normal rats (by about 50%), the dynamic coupling between the BOLD and neural responses in the cerebral cortex, as assessed by transfer function analysis, remained unaltered between the groups. However thalamic BOLD and neural responses were unaltered in AD brain compared to controls. Thus cortical responses in the AD model were indeed diminished compared to controls, but the thalamic responses in the AD and control rats were quite similar. Therefore these results suggest that Alzheimer’s disease may affect cortical function more than subcortical function, which may have implications for interpreting altered human brain functional responses in fMRI studies of Alzheimer’s disease. PMID:23648961

  17. Effect of long-term high-fat diet intake on peripheral insulin sensibility, blood pressure, and renal function in female rats

    PubMed Central

    Roza, Noemi A. V.; Possignolo, Luiz F.; Palanch, Adrianne C.; Gontijo, José A. R.

    2016-01-01

    Background This study determines whether 8-week high-fat diet (HFD) consumption alters insulin sensitivity, kidney function, and blood pressure (BP) in female rats when compared with standard rodent diet (ND) intake in gender- and age-matched rats. Methods The present study investigates, in female Wistar HanUnib rats, the effect of long-term high-fat fed group (HFD) compared with standard chow on BP by an indirect tail-cuff method using an electrosphygmomanometer, insulin and glucose function, and kidney function by creatinine and lithium clearances. Results The current study shows glucose tolerance impairment, as demonstrated by increased fasting blood glucose (ND: 78±2.8 vs. HFD: 87±3.8 mg/dL) associated with reduced insulin secretion (ND: 0.58±0.07 vs. HFD: 0.40±0.03 ng/mL) in 8-week female HFD-treated rats. The incremental area under the curve (AUC, ND: 1,4558.0±536.0 vs. HFD: 1,6507.8±661.9), homeostasis model assessment of insulin resistance (HOMA-IR) index, and the first-order rate constant for the disappearance of glucose (Kitt) were significantly enhanced in 8-week HFD-treated rats compared with age-matched ND group (respectively, P=0.03, P=0.002, and P<0.0001). The current study also shows a significantly higher systolic BP measured in 5 and 8 weeks posttreatment in HFD (5-week HFD-treated: 155.25±10.54 mmHg and 8-week HFD-treated: 165±5.8 mmHg) (P=0.0001), when compared to BP values in 5-week ND, 137±4.24 mmHg and 8-week ND, 131.75±5.8 mmHg age-matched group. Otherwise, the glomerular filtration rate and renal sodium handling evaluated by FENa, FEPNa and FEPPNa, were unchanged in both groups. Conclusion We may conclude that 8-week female HFD-fed rats compared with ND group stimulate harmful effects, such as BP rise and peripheral glucose intolerance. The increased BP occurs through insulin resistance and supposedly decreased vasodilatation response without any change on renal function. PMID:26880072

  18. Autophagic Signaling and Proteolytic Enzyme Activity in Cardiac and Skeletal Muscle of Spontaneously Hypertensive Rats following Chronic Aerobic Exercise

    PubMed Central

    McMillan, Elliott M.; Paré, Marie-France; Baechler, Brittany L.; Graham, Drew A.; Rush, James W. E.; Quadrilatero, Joe

    2015-01-01

    Hypertension is a cardiovascular disease associated with deleterious effects in skeletal and cardiac muscle. Autophagy is a degradative process essential to muscle health. Acute exercise can alter autophagic signaling. Therefore, we aimed to characterize the effects of chronic endurance exercise on autophagy in skeletal and cardiac muscle of normotensive and hypertensive rats. Male Wistar Kyoto (WKY) and spontaneously hypertensive rats (SHR) were assigned to a sedentary condition or 6 weeks of treadmill running. White gastrocnemius (WG) of hypertensive rats had higher (p<0.05) caspase-3 and proteasome activity, as well as elevated calpain activity. In addition, skeletal muscle of hypertensive animals had elevated (p<0.05) ATG7 and LC3I protein, LAMP2 mRNA, and cathepsin activity, indicative of enhanced autophagic signaling. Interestingly, chronic exercise training increased (p<0.05) Beclin-1, LC3, and p62 mRNA as well as proteasome activity, but reduced (p<0.05) Beclin-1 and ATG7 protein, as well as decreased (p<0.05) caspase-3, calpain, and cathepsin activity. Left ventricle (LV) of hypertensive rats had reduced (p<0.05) AMPKα and LC3II protein, as well as elevated (p<0.05) p-AKT, p-p70S6K, LC3I and p62 protein, which collectively suggest reduced autophagic signaling. Exercise training had little effect on autophagy-related signaling factors in LV; however, exercise training increased (p<0.05) proteasome activity but reduced (p<0.05) caspase-3 and calpain activity. Our results suggest that autophagic signaling is altered in skeletal and cardiac muscle of hypertensive animals. Regular aerobic exercise can effectively alter the proteolytic environment in both cardiac and skeletal muscle, as well as influence several autophagy-related factors in skeletal muscle of normotensive and hypertensive rats. PMID:25799101

  19. Activity of thyroxine 5' deiodinase in brown fat of lean and obese zucker rats

    SciTech Connect

    Wu, S.Y.; Fisher, D.A.; Stern, J.S.; Glick, Z.

    1986-03-01

    This study examines the possibility that the reduced brown adipose tissue (BAT) thermogenesis in the Zucker obese rat may result from a limited capacity for conversion of T/sub 4/ to T/sub 3/ in BAT, through activity of T/sub 4/ 5' deiodinase. Eighteen lean (Fa/.) and 18 age matched obese (fa/fa), about 16 weeks old, were each divided into 3 groups (n=6 per group). Group 1 and 2 were fed Purina Rat Chow and a cafeteria diet respectively for 21 days, and maintained at 22/sup 0/C+/-2. Group 3 was fed rat chow and maintained at 8/sup 0/C+/-1 for 7 days. Activity of T/sub 4/5'deiodinase was determined in vitro. T/sub 3/ was measured by a radioimmunoassay. The rate of T/sub 4/ to T/sub 3/ conversion was similar in the lean and the obese rats maintained at room temperature, whether fed rat chow or a cafeteria diet (about 40 to 50 pmol T/sub 3//scapular BAT depot, per hour). However, lean rats exposed to the cold displayed about a 5 fold increase in T/sub 4/5' deiodinase activity (p<0.0001), with only a small increase displayed by the cold exposed obese rats. Our data suggest that a reduced capacity of the brown rat to produce T/sub 3/ may account for the reduced tolerance of obese animals to cold, but it does not account for their reduced diet induced BAT thermogenesis.

  20. A new "functional" pasta containing tartary buckwheat sprouts as an ingredient improves the oxidative status and normalizes some blood pressure parameters in spontaneously hypertensive rats.

    PubMed

    Merendino, Nicolò; Molinari, Romina; Costantini, Lara; Mazzucato, Andrea; Pucci, Anna; Bonafaccia, Francesco; Esti, Marco; Ceccantoni, Brunella; Papeschi, Cristiano; Bonafaccia, Giovanni

    2014-05-01

    Epidemiological studies have reported that some foods, particularly those rich in (poly)phenols, may reduce cardiovascular risk and metabolic disorders such as hypertension. Buckwheat sprouts have been suggested as a new raw material for the production of functional foods due to their high content of healthy compounds such as rutin and quercetin. The aim of this paper is to evaluate the biological hypotensive and antioxidant responses of pasta containing tartary buckwheat sprouts (TBSP) on spontaneously hypertensive rats (SHR). In this study, dry tartary buckwheat sprouts were milled to obtain a powder that was used in the production of pasta containing 30% dry buckwheat sprouts and 70% durum wheat semolina. Afterwards, we analyzed the in vitro TBSP features compared with the control (durum wheat flour pasta, DWFP), and the in vivo effects of TBSP on SHR and their normotensive counterpart, Wistar Kyoto rats (WKY rats). The total phenolic content and antioxidant activity were higher in TBSP compared to DWFP. The results showed that SHR fed TBSP exhibited higher plasma levels of the endogenous vasodilators bradykinin (BK) and nitric oxide (NO), a lower level of the vasoconstrictor endothelin-1 (ET-1), and an improved antioxidant capacity. These data suggest that TBSP may help reduce hypertension and oxidative stress in vivo. PMID:24658587

  1. Mucosal Tolerance Induced by an Immunodominant Peptide from Rat α3(IV)NC1 in Established Experimental Autoimmune Glomerulonephritis

    PubMed Central

    Reynolds, John; Abbott, Danielle S.; Karegli, Julieta; Evans, David J.; Pusey, Charles D.

    2009-01-01

    Experimental autoimmune glomerulonephritis (EAG), an animal model of Goodpasture’s disease, can be induced in Wistar Kyoto (WKY) rats by immunization with the noncollagenous domain of the α 3 chain of type IV collagen, α3(IV)NC1. Recent studies have identified an immunodominant peptide, pCol (24-38), from the N-terminus of rat α3(IV)NC1; this peptide contains the major B- and T-cell epitopes in EAG and can induce crescentic nephritis. In this study, we investigated the mechanisms of mucosal tolerance in EAG by examining the effects of the nasal administration of this peptide after the onset of disease. A dose-dependent effect was observed: a dose of 300 μg had no effect, a dose of 1000 μg resulted in a moderate reduction in EAG severity, and a dose of 3000 μg produced a marked reduction in EAG severity accompanied by diminished antigen-specific, T-cell proliferative responses. These results demonstrate that mucosal tolerance in EAG can be induced by nasal administration of an immunodominant peptide from the N-terminus of α3(IV)NC1 and should be of value in designing new therapeutic strategies for patients with Goodpasture’s disease and other autoimmune disorders. PMID:19406992

  2. Prophylactic acetylsalicylic acid attenuates the inflammatory response but fails to protect exercise-induced liver damage in exercised rats.

    PubMed

    Huang, Kuo-Chin; Chiu, Yi-Han; Liao, Kuang-Wen; Ke, Chun-Yen; Lee, Chung-Jen; Chao, Yann-Fen C; Lee, Ru-Ping

    2016-09-01

    This study evaluated the effects of acetylsalicylic acid (ASA) on exercise-induced inflammatory response, muscle damage, and liver injury in rats. Wistar-Kyoto (WKY) rats were divided into six groups: control (C), exercise (E), C+20mg ASA, E+20mg ASA, C+100mg/kg ASA, and E+100mg ASA groups. ASA or a vehicle was orally administered through gavage 1h before a treadmill test. Upon trial completion, blood was drawn at 1, 12, and 24h for biochemical analysis, and livers were excised at 24h for a histological assessment. Our results revealed that 100mg/kg ASA significantly reduced interleukin (IL)-6 and tumor necrosis factor (TNF)-α levels in the E groups; however, the IL-10 level was considerably increased. Moreover, aspartate aminotransferase (AST), alanine aminotransferase (ALT) levels and histological hepatic damage increased significantly in the E+100mg ASA group compared with the corresponding changes in the E group. These results suggest that the prophylactic administration of particularly high-dose ASA alleviates exercise-induced inflammatory response but exacerbates liver injury. PMID:27262381

  3. Blood pressure, renal biochemical parameters and histopathology in an original rat model of essential hypertension (SHRSP/Kpo strain).

    PubMed

    Kato, Takashi; Mizuguchi, Nobuyuki; Ito, Akihiko

    2015-01-01

    Hypertensive nephropathy, a consequence of chronic high blood pressure, is increasingly a cause of end-stage renal diseases and its correct management is very important for clinical outcome. Spontaneously hypertensive rat (SHR/Kpo) and stroke-prone SHR (SHRSP/Kpo) strains represent models of human essential hypertension. However, the kidney injuries in SHR/Kpo and SHRSP/Kpo are not well defined. We therefore characterized the renal pathophysiology of SHR/Kpo and SHRSP/Kpo compared with normotensive control (WKY/Kpo) rats. The SHRSP/Kpo exhibited increased systolic blood pressure at 10 weeks of age, and proteinuria and increased blood urea nitrogen (BUN) and serum creatinine levels at 20 weeks. We simultaneously detected mononuclear cell infiltration, tubular injuries, accumulation of extracellular matrix and marked expression of α-SMA in the tubulointerstitium. Additionally, TGF-β1 and CTGF were up-regulated in the kidney of SHRSP/Kpo. We lastly focused on changes in glomerular cells of SHRSP/Kpo. Nestin, a podocyte marker, was detected but decreased slightly in 20-week-old SHRSP/Kpo. PECAM-1 expression was increased in SHRSP/Kpo glomeruli, indicating the thickening of glomerular endothelial cells. Moreover, we found that α-SMA, a myofibroblast marker, was also upregulated in the glomeruli of SHRSP/Kpo at 20 weeks. These findings suggest that SHRSP/Kpo could be a valuable animal model for human hypertensive nephropathy. PMID:26106046

  4. Differences in Retinal Structure and Function between Aging Male and Female Sprague-Dawley Rats are Strongly Influenced by the Estrus Cycle

    PubMed Central

    Chaychi, Samaneh; Polosa, Anna; Lachapelle, Pierre

    2015-01-01

    Purpose Biological sex and age are considered as two important factors that may influence the function and structure of the retina, an effect that might be governed by sexual hormones such as estrogen. The purpose of this study was to delineate the influence that biological sex and age exert on the retinal function and structure of rodents and also clarify the effect that the estrus cycle might exert on the retinal function of female rats. Method The retinal function of 50 normal male and female albino Sprague-Dawley (SD) rats was investigated with the electroretinogram (ERG) at postnatal day (P) 30, 60, 100, 200, and 300 (n = 5–6 male and female rats/age). Following the ERG recording sessions, retinal histology was performed in both sexes. In parallel, the retinal function of premenopausal and menopausal female rats aged P540 were also compared. Results Sex and age-related changes in retinal structure and function were observed in our animal model. However, irrespective of age, no significant difference was observed in ERG and retinal histology obtained from male and female rats. Notwithstanding the above we did however notice that between P60 and P200 there was a gradual increase in ERG amplitudes of female rats compared to males. Furthermore, the ERG of premenopausal female rats aged 18 months old (P540) was larger compared to age-matched menopausal female rats as well as that of male rats. Conclusion Our results showed that biological sex and age can influence the retinal function and structure of albino SD rats. Furthermore, we showed that cycled female rats have better retinal function compared to the menopausal female rats suggesting a beneficial effect of the estrus cycle on the retinal function. PMID:26317201

  5. S-Allyl cysteine improves nonalcoholic fatty liver disease in type 2 diabetes Otsuka Long-Evans Tokushima Fatty rats via regulation of hepatic lipogenesis and glucose metabolism

    PubMed Central

    Takemura, Shigekazu; Minamiyama, Yukiko; Kodai, Shintaro; Shinkawa, Hiroji; Tsukioka, Takuma; Okada, Shigeru; Azuma, Hideki; Kubo, Shoji

    2013-01-01

    It is important to prevent and improve diabetes mellitus and its complications in a safe and low-cost manner. S-Allyl cysteine, an aged garlic extract with antioxidant activity, was investigated to determine whether S-allyl cysteine can improve type 2 diabetes in Otsuka Long-Evans Tokushima Fatty rats with nonalcoholic fatty liver disease. Male Otsuka Long-Evans Tokushima Fatty rats and age-matched Long-Evans Tokushima Otsuka rats were used and were divided into two groups at 29 weeks of age. S-Allyl cysteine (0.45% diet) was administered to rats for 13 weeks. Rats were killed at 43 weeks of age, and detailed analyses were performed. S-Allyl cysteine improved hemoglobinA1c, blood glucose, triglyceride, and low-density lipoprotein cholesterol levels. Furthermore, S-allyl cysteine normalized plasma insulin levels. S-Allyl cysteine activated the mRNA and protein expression of both peroxisome proliferator-activated receptor α and γ, as well as inhibiting pyruvate dehydrogenase kinase 4 in Otsuka Long-Evans Tokushima Fatty rat liver. Sterol regulatory element-binding protein 1c and forkhead box O1 proteins were normalized by S-allyl cysteine in Otsuka Long-Evans Tokushima Fatty rat liver. In conclusions, these findings support the hypothesis that S-allyl cysteine has diabetic and nonalcoholic fatty liver disease therapeutic potential as a potent regulating agent against lipogenesis and glucose metabolism. PMID:24062606

  6. Histopathological characteristics of renal changes in human renin-angiotensinogen double transgenic rats

    PubMed Central

    Tochitani, Tomoaki; Mori, Masaya; Matsuda, Koichi; Kouchi, Mami; Fujii, Yuta; Matsumoto, Izumi

    2015-01-01

    The human renin-angiotensinogen double transgenic rat (dTGR) is a model of hypertension. The aim of this short report was to describe the histopathological characteristics of the renal changes in this rat strain in detail. Seven to nine-week-old male dTGRs were euthanized, and their kidneys were histopathologically examined. At the time of sacrifice, the average systolic blood pressure of the dTGRs was 258 mmHg, while that of age-matched, normal Sprague-Dawley rats was 135 mmHg. In the kidney, histopathological changes were observed mainly in blood vessels, tubules and glomeruli. In blood vessels, changes including medial hypertrophy, intimal thickening, hyaline change and/or fibrinoid necrosis were observed in arteries and arterioles. In tubules, changes including tubular basophilia were observed radially, mainly around interlobular arteries with lesions. In glomeruli, changes including hyaline droplet accumulation in podocytes, which was accompanied by increased expression of desmin, were observed. These changes were similar to those reported in other hypertension models, such as the spontaneously hypertensive rat (SHR). We hope that this short report will be helpful in histopathological examination of renal changes in this or other hypertension models. PMID:27182118

  7. Maturation of bone and dentin matrices in rats flown on the Soviet biosatellite Cosmos 1887

    NASA Technical Reports Server (NTRS)

    Simmons, D. J.; Grynpas, M. D.; Rosenberg, G. D.

    1990-01-01

    We have studied the chemistry, hydroxyapatite crystal size, and maturational changes in bone and dentin from rats exposed to microgravity for 12 days in a Soviet biosatellite (Cosmos 1887). Bone ash was reduced in vertebrae (L5) but not in the non-weight-bearing calvaria or mandibles. All tissues had a relatively normal percentage composition of Ca, P, and Mg. Nevertheless, flight rat calvaria and vertebral tissues tended to exhibit lower Ca/P and higher Ca/Mg ratios that any of their weight-matched controls groups, and gradient density analysis (calvaria) indicated a strong shift to the fractions lower specific gravity that was commensurate with impaired rates of matrix-mineral maturation. X-ray diffraction data were confirmatory. Bone hydroxyapatite crystal growth in the mandibles of flight rats was preferentially altered in such a way as to reduce their size (C-axis dimension). But in the mandibular diastemal region devoid of muscle attachments, flight rat bone and dentin were normal with respect to the Ca, P, Mg, and Zn concentrations and Ca/P and Ca/Mg ratios of age-matched controls. These observations affirm the concept that while microgravity most adversely affects the maturation of newly formed matrix and mineral moieties in weight-bearing bone, such effects occur throughout the skeleton.

  8. Prenatal Exposure to Lamotrigine: Effects on Postnatal Development and Behaviour in Rat Offspring

    PubMed Central

    Sathiya, Sekar; Ganesh, Murugan; Kalaivani, Periyathambi; Ranju, Vijayan; Janani, Srinivasan; Pramila, Bakthavachalam; Saravana Babu, Chidambaram

    2014-01-01

    Use of antiepileptic drugs (AEDs) in pregnancy warrants various side effects and also deleterious effects on fetal development. The present study was carried out to assess the effects of prenatal exposure to lamotrigine (LTG) on postnatal development and behavioural alterations of offspring. Adult male and female Sprague Dawley rats weighing 150–180 g b. wt. were allowed to copulate and pregnancy was confirmed by vaginal cytology. Pregnant rats were treated with LTG (11.5, 23, and 46 mg/kg, p.o) from gestational day 3 (GND 3) and this treatment continued till postnatal day 11 (PND 11). Offspring were separated from their dam on day 21 following parturition. LTG, at 46 mg/kg, p.o, produced severe clinical signs of toxicity leading to death of dam between GND 15 and 17. LTG, at 11.5 and 23 mg/kg, p.o, showed significant alterations in offspring's incisors eruption and vaginal opening when compared to age matched controls. LTG (23 mg/kg, p.o) exposed female offspring expressed hyperactive behaviour and decreased GABA-A receptor expression when compared to control rats. These results reveal that prenatal exposure to LTG may impart differential postnatal behavioural alterations between male and female rats which paves way for further investigations. PMID:24967313

  9. Histomorphometric Evaluation of the Small Coronary Arteries in Rats Exposed to Industrial Noise

    PubMed Central

    Lousinha, Ana; Antunes, Eduardo; Borrecho, Gonçalo; Oliveira, Maria João; Brito, José; Martins dos Santos, José

    2015-01-01

    Morphological changes induced by industrial noise (IN) have been experimentally observed in several organs. Histological observations of the coronary arteries showed prominent perivascular tissue and fibrosis among IN-exposed rats. The effects on the small arteries are unknown. Objective: To evaluate the histomorphometric changes induced by IN on rat heart small arteries. Methods: Twenty Wistar rats exposed to IN during a maximum period of seven months and 20 age-matched controls were studied. Hearts were transversely sectioned from ventricular apex to atria and a mid-ventricular fragment was selected for analysis. The histological images were obtained with an optical microscope using 400× magnifications. A total of 634 arterial vessels (298 IN-exposed and 336 controls) were selected. The mean lumen-to-vessel wall (L/W) and mean vessel wall-to-perivascular tissue (W/P) ratios were calculated using image J software. Results: There were no differences between exposed and control animals in their L/W ratios (p = 0.687) and time variations in this ratio were non-significant (p = 0.110). In contrast, exposed animals showed lower W/P ratios than control animals (p < 0.001), with significant time variations (p = 0.004). Conclusions: Industrial noise induced an increase in the perivascular tissue of rat small coronary arteries, with significant development of periarterial fibrosis. PMID:25946344

  10. Exercise effects on the size and metabolic properties of soleus fibers in hindlimb-suspended rats

    NASA Technical Reports Server (NTRS)

    Graham, Scot C.; Roy, Roland R.; West, Steve P.; Thomason, Don; Baldwin, Kenneth M.

    1989-01-01

    The effects of four-week-long hind-limb suspension (HS) of rats on the size the soleus muscle fibers and the activity of succinate dehydrogenase (SDH) in dark and light ATPase fibers were investigated together with the efficacy of an endurance exercise (EX) program (daily treadmill exercise for 1.5 h/day at 20 m/min and a 30-percent grade) in ameliorating HS-induced changes. It was found that, in comparison to age-matched controls, the soleus wet weight decreased by 69 and 30 percent in HS and HS-EX rats, respectively, and the percent of dark ATPase fibers increased from 10 percent in controls to 19 and 17 percent, respectively. The values of the integrated fiber activity (activity/min times muscle area) showed a net loss of SDH in both the light and dark ATPase fibers of HS rats, but only in the light ATPase fibers of the HS-EX rats, indicating that exercise ameliorated but did not prevent the muscle fiber atrophy induced by HS.

  11. ATP synthesis and export in heart left ventricle mitochondria from spontaneously hypertensive rat.

    PubMed

    Atlante, A; Seccia, T M; Pierro, P; Vulpis, V; Marra, E; Pirrelli, A; Passarella, S

    1998-04-01

    Use was made of mitochondria isolated from heart left ventricles of either spontaneously hypertensive or age-matched Wistar-Kyoto rats used as a control to find out whether hypertrophy (5-week-old rats) or hypertrophy/hypertension (24-week-old rats) can cause change in the mechanisms by which ATP is synthesised via ATP synthase and subsequently exported via the ADP/ATP translocator outside mitochondria. To do this, photometric measurements were made of the rate of ATP appearance in the extramitochondrial phase, which occurs as a result of ADP addition to mitochondria. In mitochondria from spontaneously hypertensive rats deficit of ATP production was found dependent on changes in the KmADP and Vmax values of both the ADP/ATP translocator and the ATP synthase. The ADP/ATP translocator was found to determine the rate of ATP production outside mitochondria in all the tested samples. In an initial investigation carried out to ascertain how cell ATP deficit can be counterbalanced, an increase in both adenylate kinase and creatine kinase activities was found in both hypertrophy and hypertrophy/hypertension. A possible increase in anaerobic glycolysis was also suggested by the increased lactate dehydrogenase activity. PMID:9852286

  12. Influence of spaceflight on succinate dehydrogenase activity and soma size of rat ventral horn neurons

    NASA Technical Reports Server (NTRS)

    Ishihara, A.; Ohira, Y.; Roy, R. R.; Nagaoka, S.; Sekiguchi, C.; Hinds, W. E.; Edgerton, V. R.

    1996-01-01

    Succinate dehydrogenase (SDH) activities and soma cross-sectional areas (CSA) of neurons in the dorsolateral region of the ventral horn at the L5 segmental level of the spinal cord in the rat were determined after 14 days of spaceflight and after 9 days of recovery on earth. The results were compared to those in age-matched ground-based control rats. Spinal cords were quick-frozen, and the SDH activity and CSA of a sample of neurons with a visible nucleus were determined using a digitizer and a computer-assisted image analysis system. An inverse relationship between CSA and SDH activity of neurons was observed in all groups of rats. No change in mean CSA or mean SDH activity or in the size distribution of neurons was observed following spaceflight or recovery. However, there was a selective decrease in the SDH activity of neurons with soma CSA between 500 and 800 microns2 in the flight rats, and this effect persisted for at least 9 days following return to 1 g. It remains to be determined whether the selected population of motoneurons or the specific motor pools affected by spaceflight may be restricted to specific muscles.

  13. Differential metal content and gene expression in rat left ventricular hypertrophy due to hypertension and hyperactivity.

    PubMed

    Subramanian, Meenakumari; Hunt, Adam L; Petrucci, Giuseppe A; Chen, Zengyi; Hendley, Edith D; Palmer, Bradley M

    2014-07-01

    The spontaneously hypertensive rat (SHR) has been studied extensively as a model of left ventricular hypertrophy (LVH) and associated cardiac dysfunction due to hypertension (HT). The SHR also possesses a hyperactive trait (HA). Crossbreeding SHR with Wistar-Kyoto (WKY) control rats, which are nonHT and nonHA, followed by selected inbreeding produced two additional homozygous strains: WKHT and WKHA, in which the traits of HT and HA, respectively, are expressed separately. WKHT, WKHA and SHR all display LVH, but only the SHR exhibits cardiac dysfunction. We hypothesized that cardiac dysfunction in the SHR is uniquely characterized by calcium overload. We measured total cardiac Ca, Cu, Fe, K, Mg and Zn in the four strains. We found elevated Ca and depressed Cu, Mg and Zn with HT, but not unique to SHR. We surmise that HT promotes aberrant regulation of cardiac Ca(2+), Cu(2+), Mg(2+) and Zn(2+), which does not necessarily result in cardiac dysfunction. Interestingly, Cu was elevated in HA strains compared to nonHA counterparts. We then analyzed gene expression as mRNA of Cu-containing proteins, most notably mitochondrial-Cox, Dbh, Lox, Loxl1, Loxl2, Sod1 and Tyr. The gene expression profiles of Lox, Loxl1, Loxl2 and Sod1 were found especially high in the WKHA, which if reflective of protein content could account for the high Cu content in the WKHA. The mRNA of other genes, notably Mb, Fxyd1, Maoa and Maob were also examined. We found that Maoa gene expression and monoamine oxidase-A (MAO-A) protein content were low in the SHR compared to the other strains. The finding that MAO-A protein is low in the SHR and normal in the WKHT and WKHA strains is most consistent with the idea that MAO-A protects against the development of cardiac dysfunction in LVH but not against LVH in these rats. PMID:24629670

  14. The effects of chlorpyrifos on blood pressure and temperature regulation in spontaneously hypertensive rats.

    PubMed

    Smith, Edward G; Gordon, Christopher J

    2005-06-01

    Using radiotelemetry to monitor blood pressure and core temperature, studies in our laboratory have shown that a prolonged hypertensive response is elicited in rats exposed to chlorpyrifos, an organophosphate-based insecticide. Chlorpyrifos inhibits acetylcholinesterase activity, resulting in central and peripheral stimulation of central cholinergic pathways involved in blood pressure regulation. The spontaneously hypertensive rat has been shown to be more sensitive to central cholinergic stimulation. Therefore, we hypothesized that these rats would be more susceptible and sustain a greater hypertensive response when exposed to chlorpyrifos. Heart rate, cardiac contractility, core temperature, and blood pressure were monitored by radiotelemetry in SHRs and their Wistar Kyoto (WKY) normotensive controls following exposure to chlorpyrifos (10 mg/kg or 25 mg/kg, orally). Baseline blood pressure of SHRs was approximately 35 mmHg above that of WKYs prior to dosing. SHRs exhibited a greater and more sustained elevation in diastolic, mean and systolic blood pressure following exposure to 25 mg/kg of chlorpyrifos. The rise in blood pressure lasted for approximately 56 hours in SHRs compared to approximately 32 hours in WKYs. Chlorpyrifos also led to a prolonged elevation in daytime heart rate in both strains. There was a transient elevation in cardiac contractility in both strains lasting approximately 7 hr after exposure to chlorpyrifos. The hypothermic response to chlorpyrifos was similar in magnitude and duration for both strains. Plasma cholinesterase activity measured 4 hr after exposure to 25 mg/kg chlorpyrifos was inhibited to approximately 40% of control levels in both strains. Using the SHR strain as a model to study susceptible populations, the data suggest that individuals with a genetic predisposition to hypertension may be more susceptible from exposure to organophosphate-based insecticide, as manifested by an exacerbated hypertensive response. PMID:15910416

  15. Effects of cadmium on the renal and skeletal muscle microcirculation in rats

    SciTech Connect

    Zhang Chong.

    1990-01-01

    The effects of cadmium on the arteriolar diameters of the kidney and skeletal muscle were quantified, because of the hypertensive effect of cacmium. The effect of cacmium on the constrictor response of the renal arterioles to angiotensin II (Ang II) were also assessed. In vivo preparations of the rat hydronephrotic kidney and cremaster muscle were used for direct visualization of the microvessels with intravital television microscopy. Hydronephrosis was induced in twenty-seven male Wistar-Kyoto rats (150-180 g) by unilateral ureter ligation. The hydronephrotic kidney, with intact cortical circulation and innervation, was exteriorized in a specially designed bath for microcirculation observation 6-8 weeks following the ureter ligation. The cremaster muscle experiments were conducted in another thirty-seven male WKY rats (120-180 g). Disparate effects of cadmium were observed in these two microcirculation beds. Topical cadmium (1.35 [mu]M-0.45 mM) increased the diameters of the pre- and postglomerular vessels in the hydronephrotic kidney maximally by 15-26%. Cadmium (0.27 mM) inhibited the Ang II response of the arterioles non-competitively. However, intraperitoneally injected cadmium (2 mg/kg), which significantly increased the mean arterial pressure, did not dilate the arterioles nor alter the Ang II response. On the other hand, cadmium (13.5 [mu]M-0.72 mM) constricted the larger arterioles in the cremaster muscle (60-160 [mu]m) concentration-dependently, but not small arterioles (15-30 [mu]m). In summary, topical cadmium dilates renal arterioles and decreases their reactivity to Ang II, but constricts the larger cremaster arterioles. The disparate effects of cadmium suggest different Ca[sup 2+] utilization mechanisms in different vascular beds. The construction of the cremaster arterioles may contribute to cadmium-induced hypertension by increasing peripheral resistance.

  16. Subchronic inhalation of zinc sulfate induces cardiac changes in healthy rats

    SciTech Connect

    Wallenborn, J. Grace Evansky, Paul; Shannahan, Jonathan H.; Vallanat, Beena; Ledbetter, Allen D.; Schladweiler, Mette C.; Richards, Judy H.; Gottipolu, Reddy R.; Nyska, Abraham; Kodavanti, Urmila P.

    2008-10-01

    Zinc is a common metal in most ambient particulate matter (PM), and has been proposed to be a causative component in PM-induced adverse cardiovascular health effects. Zinc is also an essential metal and has the potential to induce many physiological and nonphysiological changes. Most toxicological studies employ high levels of zinc. We hypothesized that subchronic inhalation of environmentally relevant levels of zinc would cause cardiac changes in healthy rats. To address this, healthy male WKY rats (12 weeks age) were exposed via nose only inhalation to filtered air or 10, 30 or 100 {mu}g/m{sup 3} of aerosolized zinc sulfate (ZnSO{sub 4}), 5 h/day, 3 days/week for 16 weeks. Necropsies occurred 48 h after the last exposure to ensure effects were due to chronic exposure rather than the last exposure. No significant changes were observed in neutrophil or macrophage count, total lavageable cells, or enzyme activity levels (lactate dehydrogenase, n-acetyl {beta}-D-glucosaminidase, {gamma}-glutamyl transferase) in bronchoalveolar lavage fluid, indicating minimal pulmonary effect. In the heart, cytosolic glutathione peroxidase activity decreased, while mitochondrial ferritin levels increased and succinate dehydrogenase activity decreased, suggesting a mitochondria-specific effect. Although no cardiac pathology was seen, cardiac gene array analysis indicated small changes in genes involved in cell signaling, a pattern concordant with known zinc effects. These data indicate that inhalation of zinc at environmentally relevant levels induces cardiac effects. While changes are small in healthy rats, these may be especially relevant in individuals with pre-existent cardiovascular disease.

  17. Inhaled ozone (O3)-induces changes in serum metabolomic and liver transcriptomic profiles in rats.

    PubMed

    Miller, Desinia B; Karoly, Edward D; Jones, Jan C; Ward, William O; Vallanat, Beena D; Andrews, Debora L; Schladweiler, Mette C; Snow, Samantha J; Bass, Virginia L; Richards, Judy E; Ghio, Andrew J; Cascio, Wayne E; Ledbetter, Allen D; Kodavanti, Urmila P

    2015-07-15

    Air pollution has been linked to increased incidence of diabetes. Recently, we showed that ozone (O3) induces glucose intolerance, and increases serum leptin and epinephrine in Brown Norway rats. In this study, we hypothesized that O3 exposure will cause systemic changes in metabolic homeostasis and that serum metabolomic and liver transcriptomic profiling will provide mechanistic insights. In the first experiment, male Wistar Kyoto (WKY) rats were exposed to filtered air (FA) or O3 at 0.25, 0.50, or 1.0ppm, 6h/day for two days to establish concentration-related effects on glucose tolerance and lung injury. In a second experiment, rats were exposed to FA or 1.0ppm O3, 6h/day for either one or two consecutive days, and systemic metabolic responses were determined immediately after or 18h post-exposure. O3 increased serum glucose and leptin on day 1. Glucose intolerance persisted through two days of exposure but reversed 18h-post second exposure. O3 increased circulating metabolites of glycolysis, long-chain free fatty acids, branched-chain amino acids and cholesterol, while 1,5-anhydroglucitol, bile acids and metabolites of TCA cycle were decreased, indicating impaired glycemic control, proteolysis and lipolysis. Liver gene expression increased for markers of glycolysis, TCA cycle and gluconeogenesis, and decreased for markers of steroid and fat biosynthesis. Genes involved in apoptosis and mitochondrial function were also impacted by O3. In conclusion, short-term O3 exposure induces global metabolic derangement involving glucose, lipid, and amino acid metabolism, typical of a stress-response. It remains to be examined if these alterations contribute to insulin resistance upon chronic exposure. PMID:25838073

  18. Amlodipine and atorvastatin improved hypertensive cardiac hypertrophy through regulation of receptor activator of nuclear factor kappa B ligand/receptor activator of nuclear factor kappa B/osteoprotegerin system in spontaneous hypertension rats.

    PubMed

    Lu, Jingchao; Liu, Fan; Liu, Demin; Du, Hong; Hao, Jie; Yang, Xiuchun; Cui, Wei

    2016-06-01

    The present study aims to study the role of receptor activator of nuclear factor kappa B ligand/receptor activator of nuclear factor kappa B/osteoprotegerin (RANKL/RANK/OPG) system in cardiac hypertrophy in a spontaneous hypertension rat (SHR) model and the effects of amlodipine and atorvastatin intervention. Thirty-six-week-old male SHRs were randomly divided into four groups: 1) SHR control group; 2) amlodipine alone (10 mg/kg/d) group, 3) atorvastatin alone (10 mg/kg/d) group, 4) combination of amlodinpine and atorvastatin (10 mg/kg/d for each) group. Same gender, weight, and age of Wistar-Kyoto (WKY) rats with normal blood pressure were used as normal control. Drugs were administered by oral gavage over 12 weeks. The thicknesses of left ventricle walls, left ventricle weight, and cardiac function were measured by transthoracic echocardiography. Left ventricular pressure and function were assessed by hemodynamic examination. Cardiomyocyte hypertrophy and collagen accumulation in cardiac tissue were measured by hematoxylin and eosin (HE) and Masson staining, respectively. The hydroxyproline content of cardiac tissue was examined by biochemistry technique. RANKL, RANK and OPG mRNA, protein expression and tissue localization were studied by RT-PCR, Immunohistochemistry and Western blot. Treatment with amlodipine or atorvastatin alone significantly decreased left ventricular mass index, cardiomyocyte cross-sectional area and interstitial fibrosis in SHR (each P < 0.05). Moreover, combined amlodipine and atorvastatin treatment induced significant reversal of left ventricular hypertrophy and decreased cardiomyocyte cross-sectional area and interstitial fibrosis in SHR to a greater extent than each agent alone (P < 0.05). Compared with WKY rats, the myocardial expression of RANKL, RANK, and OPG was increased. Both amlodipine and atorvastatin reduced RANKL, RANK, and OPG expression, with the best effects seen with the combination. Based on our results

  19. A study of myocardial muscarinic receptors in streptozotocin-induced diabetic rats using iodine-123 N-methyl-4-iododexetimide.

    PubMed

    Mardon, K; Kassiou, M; Katsifis, A; Najdovski, L

    1999-07-01

    In previous studies we have shown that iodine-123 N-methyl-4-iododexetimide ([123I]MIDEX) is a suitable single-photon emission tomography radiotracer for the characterisation of myocardial muscarinic acetylcholine receptors (m-AChR) in the normal state. It has been demonstrated that m-AChR are altered as a consequence of diabetes. The aim of the present study was to examine myocardial m-AChR density using [123I]MIDEX in streptozotocin (STZ)-induced diabetic rats. In vitro binding experiments were conducted on left and right ventricle and atrium homogenate membranes of 1-week, 5-week and 10-week STZ-induced diabetic and aged-matched normal rats. The m-AChR densities (Bmax values), as determined by saturation experiments with [123I]MIDEX, revealed no difference in left and right ventricles or atrium in 1-week and 5-week STZ-diabetic rats when compared with normal rats. However, the 10-week STZ-diabetic group revealed a 39% (P<0.001) decrease in m-AChR density in atrium with no change in left and right ventricles. The equilibrium dissociation constant (Kd values) was similar in all groups. In vitro binding autoradiography revealed a 40% decrease in m-AChR density in atrium in the same 10-week diabetic rats. No statistically significant difference was found in 1-week and 5-week diabetic rats compared with normals. Ex vivo autoradiography showed a 50% decrease in [123I]MIDEX uptake in atrium in 5-week diabetic rats and a 60% decrease in 10-week diabetic rats. These results demonstrate the ability of the single-photon agent [123I]MIDEX to measure in vitro and ex vivo alterations in myocardial m-AChR density observed in STZ-induced diabetic rats. PMID:10398822

  20. Lou/C obesity-resistant rat exhibits hyperactivity, hypermetabolism, alterations in white adipose tissue cellularity, and lipid tissue profiles.

    PubMed

    Soulage, Christophe; Zarrouki, Bader; Soares, Anisio Francesco; Lagarde, Michel; Geloen, Alain

    2008-02-01

    Lou/C obesity-resistant rat constitutes an original model to understand the phenomena of overweight and obesity. The aim of the present study was to identify metabolic causes for the outstanding leanness of Lou/C rat. To this end, the metabolic profiles (food intake, energy expenditure, and physical activity) and the cellular characteristics of white adipose tissue (lipogenesis, lipolysis, cellularity, and lipid composition) in 30-wk-old Lou/C rats were compared with age-matched Wistar rats. Lou/C rats exhibited a lower body weight (-45%), reduced adiposity (-80%), increased locomotor activity (+95%), and higher energy expenditure (+11%) than Wistar rats. Epididymal adipose tissue of Lou/C rat was twice lower than that of Wistar rat due to both a reduction in both adipocyte size (-25%) and number (three times). Basal lipolysis and sensitivity to noradrenaline were similar; however, the responsiveness to noradrenaline was lower in adipocytes from Lou/C compared with that from Wistar rats. Lipidomic analysis of plasma, adipose tissue, and liver revealed profound differences in lipid composition between the two strains. Of note, the desaturation indexes (ratio C16:1/C16:0 and C18:1/C18:0) were lower in Lou/C, indicating a blunted activity of delta-9-desaturase such as stearoyl-coenzyme A-desaturase-1. Increased physical activity, increased energy expenditure, and white adipose tissue cellularity are in good agreement with previous observations suggesting that a higher sympathetic tone in Lou/C could contribute to its lifelong leanness. PMID:18006635

  1. Correlates of photoreceptor rescue by transplantation of human fetal RPE in the RCS rat.

    PubMed

    Little, C W; Cox, C; Wyatt, J; del Cerro, C; del Cerro, M

    1998-01-01

    This study uses a water maze paradigm as a tool to assess posttransplantation changes in behavior associated with a visual stimulus. A set of dystrophic RCS rats received bilateral injections of freshly isolated human fetal RPE cells into the subretinal space of the superior equatorial hemisphere. Five age-matched control dystrophic RCS rats received subretinal injections of vehicle. All animals were immunosuppressed. At 2 months posttransplantation, each rat was tested in the water escape apparatus. The rat used a single light source, randomly located on the edge of the tank, to locate a submerged platform, placed directly in front of the light. Each rat was timed and videotaped during 10 consecutive trials. The swimming paths and times for all rats were recorded and statistically analyzed. Subsequent to the water escape trials, the eyes were embedded for histologic analysis which included quantitative assessment of photoreceptor cells in predefined retinal regions. The water escape data indicated the differences between the sham and experimental groups changed significantly over time (P = 0.0017). Over time, the transplanted animals learned to use light as a clue (P < 0.0001), whereas the sham animals did not (P = 0.73). Transplanted eyes had a significantly greater mean number of photoreceptors in the superior, grafted region than seen in the inferior region of the same eyes and compared with either region of sham-injected eyes (P = 0.0023). Statistical analyses demonstrated a functional advantage for visually guided behavior in RCS rats transplanted with human fetal RPE cells and a statistically significant PRC rescue effect at 2 months after transplantation. PMID:9454624

  2. Increased VGLUT3 involved in visceral hyperalgesia in a rat model of irritable bowel syndrome

    PubMed Central

    Yang, Chang-Qing; Duan, Li-Ping; Qiao, Pei-Tang; Zhao, Li; Guo, Li-Li

    2015-01-01

    AIM: To investigate the activity of vesicular glutamate transporter-3 (VGLUT3) in a visceral hyperalgesia rat model of irritable bowel syndrome, and the role of mast cells (MCs). METHODS: Transient intestinal infection was induced by oral administration of Trichinella spiralis larvae in rats. On the 100th day post-infection (PI), the rats were divided into an acute cold restraint stress (ACRS) group and a non-stressed group. Age-matched untreated rats served as controls. The abdominal withdrawal reflex was used to measure the visceromotor response to colorectal distension (CRD). The expression levels of VGLUT3 in peripheral and central neurons were analyzed by immunofluorescence and western blotting. RESULTS: VGLUT3 expression in the L6S1 dorsal root ganglion cells was significantly higher in the PI group than in the control group (0.32 ± 0.009 vs 0.22 ± 0.008, P < 0.01), and there was no significant difference in the expression of VGLUT3 between MC-deficient rats and their normal wild-type littermates. Immunofluorescence showed that the expression levels of VGLUT3 in PI + ACRS rats were enhanced in the prefrontal cortex of the brain compared with the control group. CONCLUSION: VGLUT3 is involved in the pathogenesis of visceral hyperalgesia. Coexpression of c-fos, 5-hydroxytryptamine and VGLUT3 after CRD was observed in associated neuronal pathways. Increased VGLUT3 induced by transient intestinal infection was found in peripheral nerves, and was independent of MCs. Moreover, the expression of VGLUT3 was enhanced in the prefrontal cortex in rats with induced infection and stress. PMID:25780293

  3. Altered differentiation of CNS neural progenitor cells after transplantation into the injured adult rat spinal cord.

    PubMed

    Onifer, S M; Cannon, A B; Whittemore, S R

    1997-01-01

    Denervation of CNS neurons and peripheral organs is a consequence of traumatic SCI. Intraspinal transplantation of embryonic CNS neurons is a potential strategy for reinnervating these targets. Neural progenitor cell lines are being investigated as alternates to embryonic CNS neurons. RN33B is an immortalized neural progenitor cell line derived from embryonic rat raphe nuclei following infection with a retrovirus encoding the temperature-sensitive mutant of SV40 large T-antigen. Transplantation studies have shown that local epigenetic signals in intact or partially neuron-depleted adult rat hippocampal formation or striatum direct RN33B cell differentiation to complex multipolar morphologies resembling endogenous neurons. After transplantation into neuron-depleted regions of the hippocampal formation or striatum, RN33B cells were relatively undifferentiated or differentiated with bipolar morphologies. The present study examines RN33B cell differentiation after transplantation into normal spinal cord and under different lesion conditions. Adult rats underwent either unilateral lesion of lumbar spinal neurons by intraspinal injection of kainic acid or complete transection at the T10 spinal segment. Neonatal rats underwent either unilateral lesion of lumbar motoneurons by sciatic nerve crush or complete transection at the T10 segment. At 2 or 6-7 wk postinjury, lacZ-labeled RN33B cells were transplanted into the lumbar enlargement of injured and age-matched normal rats. At 2 wk posttransplantation, bipolar and some multipolar RN33B cells were found throughout normal rat gray matter. In contrast, only bipolar RN33B cells were seen in gray matter of kainic acid lesioned, sciatic nerve crush, or transection rats. These observations suggest that RN33B cell multipolar morphological differentiation in normal adult spinal cord is mediated by direct cell-cell interaction through surface molecules on endogenous neurons and may be suppressed by molecules released after SCI

  4. No effect of hypergravity on adult rat ventral horn neuron size or SDH activity

    NASA Technical Reports Server (NTRS)

    Roy, R. R.; Ishihara, A.; Moran, M. M.; Wade, C. E.; Edgerton, V. R.

    2001-01-01

    BACKGROUND: Spaceflights of short duration (approximately 2 wk) result in adaptations in the size and/or metabolic properties of a select population of motoneurons located in the lumbosacral region of the rat spinal cord. A decrease in succinate dehydrogenase (SDH, an oxidative marker enzyme) activity of moderately sized (500-800 microm2) motoneurons in the retrodorsolateral region of the spinal cord (L6) has been observed after a 14-d flight. HYPOTHESIS: Our hypothesis was that exposure to short-term hypergravity would result in adaptations in the opposite direction, reflecting a continuum of morphological and biochemical responses in the spinal motoneurons from zero gravity to hypergravity. METHODS: Young, male rats were centrifuged at either 1.5 or 2.0 G for 2 wk. The size and SDH activity of a population of motoneurons in the retrodorsolateral region of the spinal cord (L5) were determined and compared with age-matched rats maintained at 1.0 G. The absolute and relative (to body weight) masses of the soleus, gastrocnemius, adductor longus and tibialis anterior muscles were compared among the three groups. RESULTS: There were no effects of either hypergravity intervention on the motoneuron properties. Rats maintained under hypergravity conditions gained less body mass than rats kept at 1.0 G. For the 1.5 and 2.0 G groups, the muscle absolute mass was smaller and relative mass similar to that observed in the 1.0 G rats, except for the adductor longus. The adductor longus absolute mass was similar to and the relative mass larger in both hypergravity groups than in the 1.0 G group. CONCLUSIONS: Our hypothesis was rejected. The findings suggest that rat motoneurons are more responsive to short-term chronic exposure to spaceflight than to hypergravity conditions.

  5. Type 2 diabetes alters bone and marrow blood flow and vascular control mechanisms in the ZDF rat

    PubMed Central

    Stabley, John N.; Prisby, Rhonda D.; Behnke, Bradley J.; Delp, Michael D.

    2015-01-01

    Bone health and cardiovascular function are compromised in individuals with type 2 diabetes mellitus (T2DM). The purpose of the present study was to determine whether skeletal vascular control mechanisms are altered during the progression of T2DM in the Zucker diabetic fatty (ZDF) rat. Responses of the principal nutrient artery (PNA) of the femur from obese ZDF rats with prediabetes, short-term diabetes, and long-term diabetes to endothelium-dependent (acetylcholine) and –independent (sodium nitroprusside) vasodilation, and KCl, norepinephrine and myogenic vasoconstrictor were determined in vitro. Few changes in the PNA vasomotor responses occurred in the pre-diabetic and short-term diabetic conditions. Endothelium-dependent and –independent vasodilation were reduced, and norepinephrine and myogenic vasoconstriction were enhanced in obese ZDF rats with long-term diabetes relative to lean age-matched controls. Differences in endothelium-dependent vasodilation of the femoral PNA between ZDF rats and controls were abolished by the nitric oxide synthase inhibitor NG-nitro-L-arginine methyl ester. The passive pressure-diameter response of the femoral PNA was also lower across a range of intraluminal pressures with long-term T2DM. Regional bone and marrow perfusion and vascular conductance, measured in vivo using radiolabeled microspheres, were lower in obese ZDF rats with long-term diabetes. These findings suggest that the profound impairment of the bone circulation may contribute to the osteopenia found to occur in long bones with chronic T2DM. PMID:25817711

  6. Systemic elevation of interleukin-15 in vivo promotes apoptosis in skeletal muscles of young adult and aged rats

    PubMed Central

    Pistilli, Emidio E.

    2008-01-01

    In this study, we tested the hypothesis that systemic elevation of IL-15 would attenuate apoptosis in skeletal muscles of aged rats. IL-15 was administered to young adult (n=6) and aged (n=6) rats for 14 days. Apoptosis was quantified using an ELISA assay and verified through TUNEL staining of muscle sections. As expected, apoptosis was greater in muscles from aged control rats, compared to age-matched control. Apoptosis was also greater in the muscles from young adult and aged rats treated with IL-15. These increases in apoptosis were associated with decreases in muscle mass of IL-15 treated rats. These data do not support our initial hypothesis and suggest that systemic elevation of IL-15 promotes apoptosis in skeletal muscle. The proposed anti-apoptotic property of IL-15 may be specific to cell-type and/or the degree of muscle pathology present; however, additional research is required to more clearly decipher its role in skeletal muscle. PMID:18555009

  7. Changes in the Fracture Resistance of Bone with the Progression of Type 2 Diabetes in the ZDSD Rat.

    PubMed

    Creecy, Amy; Uppuganti, Sasidhar; Merkel, Alyssa R; O'Neal, Dianne; Makowski, Alexander J; Granke, Mathilde; Voziyan, Paul; Nyman, Jeffry S

    2016-09-01

    Individuals with type 2 diabetes (T2D) have a higher fracture risk compared to non-diabetics, even though their areal bone mineral density is normal to high. Identifying the mechanisms whereby diabetes lowers fracture resistance requires well-characterized rodent models of diabetic bone disease. Toward that end, we hypothesized that bone toughness, more so than bone strength, decreases with the duration of diabetes in ZDSD rats. Bones were harvested from male CD(SD) control rats and male ZDSD rats at 16 weeks (before the onset of hyperglycemia), at 22 weeks (5-6 weeks of hyperglycemia), and at 29 weeks (12-13 weeks of hyperglycemia). There were at least 12 rats per strain per age group. At 16 weeks, there was no difference in either body weight or glucose levels between the two rat groups. Within 2 weeks of switching all rats to a diet with 48 % of kcal from fat, only the ZDSD rats developed hyperglycemia (>250 mg/dL). They also began to lose body weight at 21 weeks. CD(SD) rats remained normoglycemic (<110 mg/dL) on the high-fat diet and became obese (>600 g). From micro-computed tomography (μCT) analysis of a lumbar vertebra and distal femur, trabecular bone volume did not vary with age among the non-diabetic rats but was lower at 29 weeks than at 16 weeks or at 22 weeks for the diabetic rats. Consistent with that finding, μCT-derived intra-cortical porosity (femur diaphysis) was higher for ZDSD following ~12 weeks of hyperglycemia than for age-matched CD(SD) rats. Despite an age-related increase in mineralization in both rat strains (μCT and Raman spectroscopy), material strength of cortical bone (from three-point bending tests) increased with age only in the non-diabetic CD(SD) rats. Moreover, two other material properties, toughness (radius) and fracture toughness (femur), significantly decreased with the duration of T2D in ZDSD rats. This was accompanied by the increase in the levels of the pentosidine (femur). However, pentosidine was not

  8. The rate of ATP export in the extramitochondrial phase via the adenine nucleotide translocator changes in aging in mitochondria isolated from heart left ventricle of either normotensive or spontaneously hypertensive rats.

    PubMed

    Atlante, Anna; Seccia, Teresa Maria; Marra, Ersilia; Passarella, Salvatore

    2011-10-01

    To find out whether and how deficit of cellular energy supply from mitochondria to cytosol occurs in aging and hypertension, we used mitochondria isolated from 5 to 72 week-old heart left ventricle of either normotensive (WKY) or spontaneous hypertensive (SH) rats as a model system. Measurements were made of the rate of ATP appearance outside mitochondria, due to externally added ADP, as an increase of NADPH absorbance which occurs when ATP is produced in the presence of glucose, hexokinase and glucose-6-phosphate dehydrogenase. Such a rate proved to mirror the function of the adenine nucleotide translocator (ANT) rather than other processes linked to the both oxidative and substrate level phosphorylation. The changes in both Ki for atractyloside and Km for ADP suggest the occurrence of modification of the ANT conformation during aging in which the ANT Vmax was found to decrease in normotensive but to increase under spontaneously hypertension in 24 week-old rats with a subsequent decrease in both cases. ANT function, as investigated in the ADP physiological range (20-60μM), is expected to decrease in normotensive, but to increase in hypertensive rats up to 48 weeks. Later a decrease in the ATP rate of export outside mitochondria should occur in both cases. PMID:21855562

  9. Alpha 1-adrenoceptors mediating contraction in arteries of normotensive and spontaneously hypertensive rats are of the alpha 1D or alpha 1A subtypes.

    PubMed

    Villalobos-Molina, R; Ibarra, M

    1996-03-18

    Alpha 1-Adrenoceptor subtypes mediating contraction in carotid, aorta, mesenteric and caudal arteries from both Wistar Kyoto (WKY) normotensive and spontaneously hypertensive (SHR) rats were investigated by using the alpha 1A-adrenoceptor agonist methoxamine and antagonized with selective, competitive antagonists WB-4101, 5-methyl urapidil or BMY 7378 (8-(4-(2-methoxyphenyl)-1-piperazinyl)ethyl)-8-azaspiro(4,5)decane -7,9-dione dihydrochloride). Isometric tension changes were recorded after methoxamine addition to the arterial rings, and the effects of the antagonists determined. All the antagonists shifted to the right the concentration-response curve to methoxamine. pA2 values indicate that all arteries but caudal express the alpha 1D-adrenoceptor subtype, since BMY 7378 values were high in these arteries. Due to the high pA2 values for 5-methyl urapidil and WB-4101 and the low values for BMY 7378 we conclude that the tail artery expresses the alpha 1A and not the alpha 1B subtype. No differences were found between both strains of rats, suggesting that hypertension does not modify the alpha 1-adrenoceptors in conductance arteries. PMID:8846824

  10. Testosterone enhancement of thyroid carcinoma in rats: the role of TSH

    SciTech Connect

    Hofmann, C.; Oslapas, R.; Nayyar, R.; McCall, A.; Paloyan, E.

    1986-12-01

    Radiation treatment of Long-Evans male rats (40 mu Ci Na131I at the age of 2 months) led to a high incidence of thyroid follicular carcinomas at the age of 24 months; castration of males before irradiation caused a significant reduction in incidence of this tumor. In this study, replacement testosterone (T) was administered to castrated male rats by means of implanted, slow-release hormone-containing pellets (T-physiologic dose). Three testosterone doses (0.1T, 1.0T, and 30T) were used to treat groups of castrated irradiated and castrated nonirradiated rats from 2 to 18 months of age. The incidence of thyroid follicular carcinoma at 18 months in irradiated rats depended on the dose of replacement testosterone used. Tumor incidence was 8%, 14%, 41%, and 50% after treatment with 0T, 0.1T, 1.0T, and 30T, respectively. The incidence of thyroid follicular carcinoma in nonirradiated rats ranged from 0 to 7%. Mean serum thyroid-stimulating hormone (TSH) values in irradiated animal groups were elevated significantly above those for age-matched nonirradiated animals. The degree of TSH elevation in irradiated animals was related directly to the testosterone-replacement level. All rat groups showed age-dependent decreases in serum T4 levels, and T4 levels were also lowered by replacement testosterone in nonirradiated castrated animals. In aging irradiated animals, serum T4 levels were similarly decreased by testosterone, despite elevated TSH levels in these groups. In this study, testosterone appeared to act indirectly to promote development of irradiation-induced thyroid tumors by early and prolonged elevation of TSH levels.

  11. A2B Adenosine Receptor Agonist Improves Erectile Function in Diabetic Rats.

    PubMed

    Wen, Jiaming; Wang, Bohan; Du, Chuanjun; Xu, Gang; Zhang, Zhewei; Li, Yi; Zhang, Nan

    2015-01-01

    Diabetes is an important risk factor for erectile dysfunction (ED). Recent studies have indicated that A2B adenosine receptor (ADORA2B) signaling is essential for penile erection. Thus, we hypothesize that diabetic ED may be attributed to impaired A2B adenosine signaling. To test this hypothesis, we generated diabetic rats by injecting streptozocin as animal model. After 12 weeks, immunohistochemistry staining was used to localize the expression of ADORA2B. Western Blot and quantitative PCR were employed to determine ADORA2B expression level. Intracavernosal pressure (ICP) measurement was used to evaluate erectile function. Diabetic rats received a single intravenous injection of BAY 60-6583, an ADORA2B agonist, or vehicle solution, at 60 min before the ICP measurement. The results showed that ADORA2B expressed in the nerve bundle, smooth muscle, and endothelium in penile tissue of control mice. Western Blot and quantitative PCR results indicated that the expression levels of ADORA2B protein and mRNA were significantly reduced in penile tissues of diabetic rats. Functional studies showed that the erectile response induced by electrical stimulation was remarkably decreased in diabetic rats, compared with age-matched control rats. However, at 60 min after BAY 60-6583 treatment, the erectile function was improved in diabetic rats, suggesting that enhancement of ADORA2B signaling may improve erectile function in diabetic ED. This preclinical study has revealed a previously unrecognized therapeutic possibility of BAY 60-6583 as an effective and mechanism-based drug to treat diabetic ED. In conclusion, we propose that impaired A2B adenosine signaling is one of the pathological mechanisms of diabetic ED. PMID:26447087

  12. Hepatic Isoprenoid Metabolism in a Rat Model of Smith-Lemli-Opitz Syndrome

    PubMed Central

    Keller, R. Kennedy; Mitchell, David A.; Goulah, Christopher C.

    2013-01-01

    Elevated (4 to 7-fold) levels of urinary dolichol and coenzyme Q and substantially longer chain lengths for urinary dolichols have been reported in Smith-Lemli-Opitz Syndrome (SLOS) patients, compared to normal subjects. We investigated the possibility of similar alterations in hepatic, nonsterol isoprenoids in a well-established rat model of SLOS. In this model, the ratio of 7-dehydrocholesterol (7DHC) to cholesterol (Chol) in serum approached 15:1; however, total sterol mass in serum decreased by >80 %. Livers from treated rats had 7DHC/Chol ratios of ~32:1, but the steady-state levels of total sterols were >40 % those of livers from age-matched (3-month-old) control animals. No significant differences in the levels of LDL receptor or HMG-CoA reductase were observed. The levels of dolichol and coenzyme Q were elevated only modestly (by 64 and 31 %, respectively; p < 0.05, N = 6) in the livers of the SLOS rat model compared to controls; moreover, the chain lengths of these isoprenoids were not different in the two groups. We conclude that hepatic isoprenoid synthesis is marginally elevated in this animal model of SLOS, but without preferential shunting to the nonsterol branches (dolichol and coenzyme Q) of the pathway and without alteration of normal dolichol chain lengths. PMID:23361583

  13. Inhibiting Amadori-modified albumin formation improves biomarkers of podocyte damage in diabetic rats

    PubMed Central

    Cohen, Margo P; Shearman, Clyde W

    2013-01-01

    Recent studies have shown that urinary excretion of podocyte proteins is an indicator of podocyte injury, and that podocyte abnormalities and elevated concentrations of Amadori-modified glycated albumin (AGA) are linked to the development of diabetic nephropathy and to each other. We evaluated relationships between urinary markers of podocyte damage, increased AGA and filtration function in rats made diabetic by streptozotocin injection and treated for 8 weeks with a compound that inhibits the formation of AGA, with age-matched nondiabetic and diabetic rats serving as controls. Blood and urine were collected for measurement of glycated albumin, creatinine, albumin, nephrin, podocalyxin, and βig-h3 protein. The elevated circulating concentrations of glycated albumin and higher urinary levels of these podocyte markers as well as of albumin that were observed in diabetic rats compared with nondiabetic controls were significantly reduced in animals receiving test compound, and decrease in urinary biomarkers correlated with reduction in AGA. The results provide evidence that lowering the concentration of AGA, independent of filtration status and hyperglycemia, reduces urinary nephrin, podocalyxin, and βig-h3 protein, linking the increased glycated albumin associated with diabetes to podocyte abnormalities and shedding of podocyte proteins into the urine. PMID:24303153

  14. Decreased catecholamine secretion from the adrenal medullae of chronically diabetic BB-Wistar rats

    NASA Technical Reports Server (NTRS)

    Wilke, R. A.; Riley, D. A.; Lelkes, P. I.; Hillard, C. J.

    1993-01-01

    Many humans with IDDM eventually lose the capacity to secrete epinephrine from their adrenal medullae. The mechanism for this pathological change is unknown. We hypothesized that this abnormality is attributable to neuropathic changes in the greater splanchnic nerves or in the chromaffin cells that they innervate. To study this hypothesis, we isolated rat adrenal glands, perfused them ex vivo, and measured the epinephrine content of the perfusate under various conditions of stimulation. We used transmural electrical stimulation (20-80 V, at 10 Hz) to induce epinephrine secretion indirectly by selectively activating residual splanchnic nerve terminals within the isolated glands. Under these conditions, epinephrine secretion was severely attenuated in glands from female BB-Wistar rats with diabetes of 4 mo duration compared with their age-matched, nondiabetic controls. These perfused diabetic adrenal medullae also demonstrated decreased catecholamine release in response to direct chromaffin cell depolarization with 20 mM K+, evidence that a functional alteration exists within the chromaffin cells themselves. Nonetheless, total catecholamine content of adrenal medullae from these diabetic rats was not significantly different from controls, indicating that the secretory defect was not simply attributable to a difference in the amount of catecholamines stored and available for release. Herein, we also provide histological evidence of degenerative changes within the cholinergic nerve terminals that innervate these glands.

  15. Effects of Spaceflight on Bone Microarchitecture in the Axial and Appendicular Skeleton in Growing Ovariectomized Rats

    PubMed Central

    Keune, Jessica A.; Branscum, Adam J.; Iwaniec, Urszula T.; Turner, Russell T.

    2015-01-01

    This study investigated the effects of a 14-day spaceflight on bone mass, density and microarchitecture in weight bearing (femur and humerus) and non-weight bearing (2nd lumbar vertebra and calvarium) bones in the context of ovarian hormone insufficiency. 12-week-old Fisher 344 rats were ovariectomized 2 weeks before flight and randomized into one of three groups: 1) baseline (n = 6), 2) ground control (n = 12) or 3) spaceflight (n = 12). Additional ground-based ovary-intact rats provided age-matched reference values at baseline (n = 8) and landing (n = 10). Ovariectomy resulted in bone- and bone compartment-specific deficits in cancellous bone volume fraction. Spaceflight resulted in lower cortical bone accrual in the femur but had no effect on cortical bone in the humerus or calvarium. Cancellous bone volume fraction was lower in flight animals compared to ground control animals in lumbar vertebra and distal femur metaphysis and epiphysis; significant differences were not detected in the distal humerus. Bone loss (compared to baseline controls) in the femur metaphysis was associated with lower trabecular number, whereas trabecular thickness and number were lower in the epiphysis. In summary, the effect of spaceflight on bone microarchitecture in ovariectomized rats was bone-and bone compartment-specific but not strictly related to weight bearing. PMID:26691062

  16. Altered response of protein synthesis to nutritional state and endurance training in old rats.

    PubMed

    Mosoni, L; Valluy, M C; Serrurier, B; Prugnaud, J; Obled, C; Guezennec, C Y; Mirand, P P

    1995-02-01

    This study was undertaken to determine whether the loss of muscle protein mass during aging could be explained by a reduced sensitivity of muscle protein synthesis to feeding and exercise. Male Wistar rats aged 12 and 24 mo were exercised by treadmill running for 4 mo. Protein synthesis was measured by the flooding dose method in tibialis anterior, soleus, and liver of conscious rested, trained rats and age-matched controls in the postprandial or in the postabsorptive state. No marked change with age could be detected in basal muscle protein synthesis. In contrast, protein synthesis was stimulated in adult but not in old rats by feeding in tibialis anterior and by exercise in soleus. In liver, protein synthesis was not modified by age but was stimulated by feeding and by exercise, which improved the response to feeding. We conclude that the impact of nutrition on muscle protein synthesis is blunted in old age, which could contribute to the age-related loss of nutrition-sensitive muscle proteins. PMID:7864110

  17. Distribution of calcium in the rat due to chronic renal failure.

    PubMed

    Ellis, K J; Martino, A; Yasumura, S; Brook, D; Cohn, S H; Letteri, J M

    1977-01-01

    During the 12 weeks following 5/6 nephrectomy in rats with moderate uremia (creatinine 0.7-1.2 mg/100 ml, BUN 53-89 mg/100 ml), no significant increases in total soft tissue calcification were observed. The calcium concentration of skeletal muscle remained unchanged at 4, 8, and 12 weeks after surgery. A slight but not significant increase in skin calcium was found. However, a significant decrease in cardiac calcium was found for the uremic animals. Total body calcium as determined by neutron activation analysis was significantly lower in the uremic rat when compared with the age-matched animal. However, when normalized for body weight, the total calcium content in uremic rats did not differ from the controls. Similar findings were observed for the absolute calcium content of the tibia and when normalized for weight. Furthermore, a highly significant linear relationship (r = 0.92, p less than 0.001) was established between absolute levels of total body calcium and tibia calcium which was identical for control and uremic groups. PMID:854140

  18. Ultrastructural changes in the hypothalamic supraoptic nucleus of the streptozotocin-induced diabetic rat.

    PubMed Central

    Dheen, S T; Tay, S S; Wong, W C

    1994-01-01

    Ultrastructural and morphometric studies were undertaken on the hypothalamic supraoptic nucleus of streptozotocin-induced diabetic rats over a period of 1 y. At 3 d, a few dendrites showing electron-dense cytoplasm and dilated rER were dispersed in the neuropil among seemingly normal neuronal somata. At 1-6 months, the somata contained numerous vacuoles of various sizes which probably originated from fragmented and dilated rER. Numerous unidentifiable vacuolated and electron-dense neuronal profiles were also seen in the neuropil. At 9-12 months, the number of degenerating electron-dense axon terminals and dendrites was markedly increased in diabetic rats. Glial cells containing electron-dense debris in their cytoplasm were involved in phagocytosis. At all time intervals studied, the mean cross-sectional cell area and mean cross-sectional nuclear area of supraoptic nuclei neurons of diabetic rats were significantly increased in comparison with age-matched controls injected with normal saline. The causative factors for these changes are not clear. However, it is suggested that the osmotic stress caused by chronic dehydration in the diabetic animals may be partly or wholly responsible for these ultrastructural changes. Images Fig. 1 Fig. 2 Fig. 3 Fig. 4 Fig. 5 Fig. 6 Fig. 7 Fig. 8 Fig. 9 PMID:7928649

  19. Effects of triclocarban on intact immature male rat: augmentation of androgen action.

    PubMed

    Duleba, Antoni J; Ahmed, Mohamed I; Sun, Meng; Gao, Allen C; Villanueva, Jesus; Conley, Alan J; Turgeon, Judith L; Benirschke, Kurt; Gee, Nancy A; Chen, Jiangang; Green, Peter G; Lasley, Bill L

    2011-02-01

    Triclocarban (TCC; 3,4,4'-trichlorocarbanilide) is an antimicrobial agent used widely in various personal hygiene products including soaps. Recently, TCC has been shown to enhance testosterone-induced effects in vitro and to enlarge accessory sex organs in castrated male rats. This study was designed to evaluate the effects of TCC on intact age-matched male rats and on human prostate LNCaP and C4-2B cells. Seven-week-old male Sprague-Dawley rats received either a normal diet or a diet supplemented with TCC (0.25% in diet) for 10 days. Triclocarban induced hyperplasia of accessory sex organs in the absence of significant qualitative histological changes. Serum luteinizing hormone (LH) and testosterone were not significantly altered by TCC treatment. In prostate cancer-derived LNCaP and C4-2B cells, TCC potentiated androgen actions via androgen receptor-dependent actions. In conclusion, TCC significantly affects intact male reproductive organs and potentiates androgen effects in prostate cancer cells. PMID:20889956

  20. Vascular Injury After Whole Thoracic X-Ray Irradiation in the Rat

    SciTech Connect

    Ghosh, S.N. Wu, Q. M.S.; Maeder, M.; Fish, B.L.; Moulder, J.E.; Jacobs, E.R.; Medhora, M.; Molthen, R.C.

    2009-05-01

    Purpose: To study vascular injury after whole thoracic irradiation with single sublethal doses of X-rays in the rat and to develop markers that might predict the severity of injury. Methods and Materials: Rats that received 5- or 10-Gy thorax-only irradiation and age-matched controls were studied at 3 days, 2 weeks, and 1, 2, 5, and 12 months. Several pulmonary vascular parameters were evaluated, including hemodynamics, vessel density, total lung angiotensin-converting enzyme activity, and right ventricular hypertrophy. Results: By 1 month, the rats in the 10-Gy group had pulmonary vascular dropout, right ventricular hypertrophy, increased pulmonary vascular resistance, increased dry lung weights, and decreases in total lung angiotensin-converting enzyme activity, as well as pulmonary artery distensibility. In contrast, irradiation with 5 Gy resulted in only a modest increase in right ventricular weight and a reduction in lung angiotensin-converting enzyme activity. Conclusion: In a previous investigation using the same model, we observed that recovery from radiation-induced attenuation of pulmonary vascular reactivity occurred. In the present study, we report that deterioration results in several vascular parameters for {<=}1 year after 10 Gy, suggesting sustained remodeling of the pulmonary vasculature. Our data support clinically relevant injuries that appear in a time- and dose-related manner after exposure to relatively low radiation doses.

  1. [Chronological analyses of neuropathological and molecular biological changes in affected spinal cord of HTLV-I-infected rat (HAM rat disease)].

    PubMed

    Ohya, O

    2000-03-01

    The author chronologically analyzed neuropathological aspects of the demyelination process in spinal cords of a rat model of human T-cell leukemia virus type I (HTLV-I)-associated myelopathy/tropical spastic paraparesis (HAM/TSP) from early asymptomatic to late disease stage for clarifying the pathogenetic roles of HTLV-I in central nervous system. There was no significant difference in histopathological and immunohistochemical findings between the rats within 7 months after the HTLV-I infection and age-matched controls. The first sign of demyelination was the appearance of apoptotic cell death beginning at 7 months after the infection and the apoptotic cell number gradually increased to 12 cells per a whole horizontal section of the spinal cord, in contrast to 5 cells in the control rats. The majority of the apoptotic cells were shown to be oligodendrocytes by immunohistochemical stain with an anti-myelin oligodendrocyte glycoprotein antibody. Increment of activated microglia/macrophages started at 9 months after the infection and they rapidly increased from 15 months to reach 600 cells per a whole horizontal section, in contrast to 300 cells in the control rats. Rapid increase of gemistocytic astrocytes was found from 20 months after the infection (the late disease stage). Molecular analysis of the spinal cords revealed that HTLV-I provirus DNA was evident as early as 4 months after the infection, and massages of HTLV-I pX and tumor necrosis factor (TNF)-alpha began to be expressed at 7 months, just before or at the same time as the appearance of the apoptotic cells. The collective evidence suggests that the apoptotic death of oligodendrocytes, which may be induced either directly by the local expression of HTLV-I or indirectly by upregulated cytotoxic humoral mediators, such as TNF-alpha, through the transactive function of p40 Tax, is the major cause of chronic progressive myelopathy in WKAH rats with HTLV-I infection. PMID:10791252

  2. Pregnant rats treated with a high-fat/prooxidant Western diet with ANG II and TNF-α are resistant to elevations in blood pressure and renal oxidative stress

    PubMed Central

    West, Crystal A.; Wen, Xuerong; Deng, Aihua; Baylis, Chris

    2015-01-01

    Oxidative stress and inflammation are risk factors for hypertension in pregnancy. Here, we examined the 24-h mean arterial pressure (MAP) via telemetry and the nitric oxide (NO) and redox systems in the kidney cortex, medulla, and aorta of virgin and pregnant rats treated with a high-fat/prooxidant Western diet (HFD), ANG II, and TNF-α. Female Sprague-Dawley rats were given a normal diet (ND) or a HFD for 8 wk before mating. Day 6 of pregnancy and age-matched virgins were implanted with minipumps infusing saline or ANG II (150 ng·kg−1·min−1) + TNF-α (75 ng/day) for 14 days. Groups consisted of Virgin + ND + Saline (V+ND) (n = 7), Virgin + HFD +ANG II and TNF-α (V+HFD) (n = 7), Pregnant + ND + Saline (P+ND) (n = 6), and Pregnant + HFD + ANG II and TNF-α (P+HFD) (n = 8). After day 6 of minipump implantation, V+HFD rats displayed an increase in MAP on days 7, 8, and 10–15 vs. V+ND rats. P+HFD rats, after day 6 of minipump implantation, showed an increase in MAP only on day 7 vs. P+ND rats. P+HFD rats had a normal fall in 24-h MAP, hematocrit, plasma protein concentration, and osmolality at late pregnancy. No change in kidney cortex, medulla, or aortic oxidative stress in P+HFD rats. P+HFD rats displayed a decrease in nNOSβ abundance, but no change in kidney cortex NOx content vs. P+ND rats. Pregnant rats subjected to a chronic HFD and prooxidant and proinflammatory insults have a blunted increase in 24-h MAP and renal oxidative stress. Our data suggest renal NO bioavailability is not altered in pregnant rats treated with a HFD, ANG II, and TNF-α. PMID:25810384

  3. Potassium conductance and oscillatory contractions in tail arteries from genetically hypertensive rats.

    PubMed

    Lamb, F S; Webb, R C

    1989-06-01

    Tail arteries isolated from the stroke-prone substrain of the spontaneously hypertensive rat (SHR-SP) exhibit oscillatory contractile responses to norepinephrine. Simultaneous recording of force generation and membrane potential (Em) has previously demonstrated that the contractile phase of these oscillations is associated with bursts of calcium-dependent action potentials. The smooth muscle cells are electrically quiescent during the relaxation phase of the oscillations. The present studies were designed to test the hypothesis that this quiescent period results from the stimulation of a calcium-activated potassium conductance (gKCa) in the cells responsible for triggering the bursting activity. Isolated tail artery strips from SHR-SP and Wistar-Kyoto rats (WKY) were prepared for measurement of isometric force generation or for simultaneous recording of force and Em. The channel-specific toxins apamin (4 x 10(-7) mol/l) and charybdotoxin (4.7 x 10(-8) did not alter the oscillatory pattern of contraction in response to norepinephrine. Oscillations were converted to sustained contraction by barium (10(-4) mmol), quinidine (5.8 x 10(-5) mmol) and elevation of extracellular potassium (20 mmol/l). Em recordings show that both potassium and barium convert bursting activity into tonic firing. Only 20 mmol/k+ caused significant depolarization in addition to that produced by norepinephrine. In contrast, quinidine appears to alter oscillatory behavior by interfering with calcium-spike generation. Norepinephrine-induced electrical activity is diminished in the presence of quinidine. These results suggest that potassium conductance plays an important role in controlling Em, electrical spiking and therefore oscillatory contractile activity in response to norepinephrine in the tail arteries of SHR-SP.(ABSTRACT TRUNCATED AT 250 WORDS) PMID:2778313

  4. Dietary calcium and magnesium supplements in spontaneously hypertensive rats and isolated arterial reactivity.

    PubMed Central

    Mäkynen, H.; Kähönen, M.; Arvola, P.; Wuorela, H.; Vapaatalo, H.; Pörsti, I.

    1995-01-01

    1. High calcium diet attenuates the development of hypertension but an associated undesirable effect is that Mg2+ loss to the urine is enhanced. Therefore, we studied the effects of high calcium diet alone and in combination with increased magnesium intake on blood pressure and arterial function. 2. Forty-eight young spontaneously hypertensive rats (SHR) were allocated into four groups, the dietary contents of Ca2+ and Mg2+ being: 1.1%, 0.2% (SHR); 2.5%, 0.2% (Ca-SHR); 2.5%, 0.8% (CaMg-SHR); and 1.1%, 0.8% (Mg-SHR), respectively. Development of hypertension was followed for 13 weeks, whereafter electrolyte balance, lymphocyte intracellular free calcium ([Ca2+]i), and mesenteric arterial responses in vitro were examined. Forty normotensive Wistar-Kyoto (WKY) rats were investigated in a similar manner. 3. Calcium supplementation comparably attenuated the development of Lypertension during normal and high magnesium intake in SHR, with an associated reduced lymphocyte [Ca2+]i and increased Mg2+ loss to the urine. 4. Endothelium-dependent arterial relaxation to acetylcholine was augmented in Ca-SHR and CaMg-SHR, while the relaxations to isoprenaline and the nitric oxide donor SIN-1 were similar in all SHR groups. Relaxation responses induced by the return of K+ to the organ bath upon precontractions in K(+)-free solution were used to evaluate the function of arterial Na+, K(+)-ATPase. The rate of potassium relaxation was similar in Ca-SHR and CaMg-SHR and faster than in untreated SHR.(ABSTRACT TRUNCATED AT 250 WORDS) PMID:8564205

  5. Role(s) of gravitational loading during developing period on the growth of rat soleus muscle fibers.

    PubMed

    Kawano, Fuminori; Goto, Katsumasa; Wang, Xiao Dong; Terada, Masahiro; Ohira, Takashi; Nakai, Naoya; Yoshioka, Toshitada; Ohira, Yoshinobu

    2010-03-01

    Effects of gravitational loading or unloading on the gain of the characteristics in soleus muscle fibers were studied in rats. The tail suspension was performed in newborn rats from postnatal day 4 to month 3, and the reloading was allowed for 3 mo in some rats. Single expression of type I myosin heavy chain (MHC) was observed in approximately 82% of fibers in 3-mo-old controls, but the fibers expressing multiple MHC isoforms were noted in the unloaded rats. Although 97% of fibers in 3-mo-old controls had a single neuromuscular junction at the central region of fiber, fibers with multiple nerve endplates were seen in the unloaded group. Faster contraction speed and lower maximal tension development, even after normalization with fiber size, were observed in the unloaded pure type I MHC fibers. These parameters generally returned to the age-matched control levels after reloading. It was suggested that antigravity-related tonic activity plays an important role in the gain of single neural innervation and of slow contractile properties and phenotype in soleus muscle fibers. PMID:20056853

  6. Role(s) of Gravitational Loading on the Growth-Related Transformation of Fiber Phenotype in Rat Soleus

    NASA Astrophysics Data System (ADS)

    Ohira, Yoshinobu; Kawano, Fuminori; Goto, Katsumasa; Terada, Masahiro; Ohira, Takashi; Nakai, Naoya; Higo, Yoko; Yoshioka, Toshitada

    2008-06-01

    Effects of gravitational loading or unloading on the gain of the characteristics in soleus muscle fibers were studied in rats. The tail suspension was performed in newborn rats from the postnatal day 4 to month 3 and the reloading was allowed for 3 months in some rats. Single expression of type I myosin heavy chain (MHC) was observed in ~82% fibers in 3month old controls, but fibers expressing multiple MHC iso-forms were noted in the unloaded rats. Responses of fast or slow MHC protein expression to growth and/or unloading were not directly related to mRNA expression. Although 97% fibers in 3month old controls had a single neuromuscular junction at the central region of fiber, fibers with multiple nerve endplates were seen in the unloaded group. Faster contraction speed and lower maximal tension development, even after normalization with fiber size, were observed in the unloaded pure type I MHC fibers. These parameters generally returned to the age-matched control levels after reloading. It was suggested that antigravity-related tonic activity plays an important role in the gain of single neural innervation and of slow contractile properties and phenotype in soleus muscle fibers, which are not directly related to gene expression.

  7. Chronic in vivo or acute in vitro resveratrol attenuates endothelium-dependent cyclooxygenase-mediated contractile signaling in hypertensive rat carotid artery.

    PubMed

    Denniss, Steven G; Ford, Rebecca J; Smith, Christopher S; Jeffery, Andrew J; Rush, James W E

    2016-05-15

    Exaggerated cyclooxygenase (COX) and thromboxane-prostanoid (TP) receptor-mediated endothelium-dependent contraction can contribute to endothelial dysfunction. This study examined the effect of resveratrol (RSV) on endothelium-dependent contraction and cell signaling in the common carotid artery (CCA) from spontaneously hypertensive rats (SHR) and Wistar Kyoto rats (WKY). Acetylcholine (Ach)-stimulated endothelium-dependent nitric oxide synthase (NOS)-mediated relaxation in precontracted SHR CCA was impaired (maximum 73 ± 6% vs. 87 ± 5% in WKY) (P < 0.05) by competitive COX-mediated contraction. Chronic (28-day) treatment in vivo (drinking water) with a ∼0.075 mg·kg(-1)·day(-1) RSV dose affected neither endothelium-dependent relaxation nor endothelium-dependent contraction and associated prostaglandin (PG) production evaluated in non-precontracted NOS-blocked CCA. In contrast, a chronic ∼7.5 mg·kg(-1)·day(-1) RSV dose improved endothelium-dependent relaxation (94 ± 6%) and attenuated endothelium-dependent contraction (58 ± 4% vs. 73 ± 5% in No-RSV) and PG production (183 ± 43 vs. 519 ± 93 pg/ml) in SHR CCA, while U46619-stimulated TP receptor-mediated contraction was unaffected. In separate acute in vitro experiments, 20-μM RSV preincubation attenuated endothelium-dependent contraction (6 ± 4% vs. 62 ± 2% in No Drug) and PG production (121 ± 15 vs. 491 ± 93 pg/ml) and attenuated U46619-stimulated contraction (134 ± 5% vs. 171 ± 4%) in non-precontracted NOS-blocked SHR CCA. Compound C, a known AMP-activated protein kinase (AMPK) inhibitor, did not prevent the RSV attenuating effect on Ach- and U46619-stimulated contraction but did prevent the RSV attenuating effect on PG production (414 ± 58 pg/ml). These data demonstrate that RSV can attenuate endothelium-dependent contraction both by suppressing arterial wall PG production, which may be partially mediated by AMPK, and by TP receptor hyporesponsiveness, which does not appear to be mediated by

  8. Effects of high-intensity swimming training on GLUT-4 and glucose transport activity in rat skeletal muscle.

    PubMed

    Terada, S; Yokozeki, T; Kawanaka, K; Ogawa, K; Higuchi, M; Ezaki, O; Tabata, I

    2001-06-01

    This study was performed to assess the effects of short-term, extremely high-intensity intermittent exercise training on the GLUT-4 content of rat skeletal muscle. Three- to four-week-old male Sprague-Dawley rats with an initial body weight ranging from 45 to 55 g were used for this study. These rats were randomly assigned to an 8-day period of high-intensity intermittent exercise training (HIT), relatively high-intensity intermittent prolonged exercise training (RHT), or low-intensity prolonged exercise training (LIT). Age-matched sedentary rats were used as a control. In the HIT group, the rats repeated fourteen 20-s swimming bouts with a weight equivalent to 14, 15, and 16% of body weight for the first 2, the next 4, and the last 2 days, respectively. Between exercise bouts, a 10-s pause was allowed. RHT consisted of five 17-min swimming bouts with a 3-min rest between bouts. During the first bout, the rat swam without weight, whereas during the following four bouts, the rat was attached to a weight equivalent to 4 and 5% of its body weight for the first 5 days and the following 3 days, respectively. Rats in the LIT group swam 6 h/day for 8 days in two 3-h bouts separated by 45 min of rest. In the first experiment, the HIT, LIT, and control rats were compared. GLUT-4 content in the epitrochlearis muscle in the HIT and LIT groups after training was significantly higher than that in the control rats by 83 and 91%, respectively. Furthermore, glucose transport activity, stimulated maximally by both insulin (2 mU/ml) (HIT: 48%, LIT: 75%) and contractions (25 10-s tetani) (HIT: 55%, LIT: 69%), was higher in the training groups than in the control rats. However, no significant differences in GLUT-4 content or in maximal glucose transport activity in response to both insulin and contractions were observed between the two training groups. The second experiment demonstrated that GLUT-4 content after HIT did not differ from that after RHT (66% higher in trained rats than

  9. Modeling fibrosis using fibroblasts isolated from scarred rat vocal folds.

    PubMed

    Kishimoto, Yo; Kishimoto, Ayami Ohno; Ye, Shuyun; Kendziorski, Christina; Welham, Nathan V

    2016-07-01

    Following injury, pathologically activated vocal fold fibroblasts (VFFs) can engage in disordered extracellular matrix (ECM) remodeling, leading to VF fibrosis and impaired voice function. Given the importance of scar VFFs to phenotypically appropriate in vitro modeling of VF fibrosis, we pursued detailed characterization of scar VFFs obtained from surgically injured rat VF mucosae, compared with those obtained from experimentally naïve, age-matched tissue. Scar VFFs initially exhibited a myofibroblast phenotype characterized by increased proliferation, increased Col1a1 transcription and collagen, type I synthesis, increased Acta2 transcription and α-smooth muscle actin synthesis, and enhanced contractile function. These features were most distinct at passage 1 (P1); we observed a coalescence of the scar and naïve VFF phenotypes at later passages. An empirical Bayes statistical analysis of the P1 cell transcriptome identified 421 genes that were differentially expressed by scar, compared with naïve, VFFs. These genes were primarily associated with the wound response, ECM regulation, and cell proliferation. Follow-up comparison of P1 scar VFFs and their in vivo tissue source showed substantial transcriptomic differences. Finally, P1 scar VFFs responded to treatment with hepatocyte growth factor and transforming growth factor-β3, two biologics with reported therapeutic value. Despite the practical limitations inherent to working with early passage cells, this experimental model is easily implemented in any suitably equipped laboratory and has the potential to improve the applicability of preclinical VF fibrosis research. PMID:27111284

  10. Fine structural abnormalities of the placenta in diabetic rats.

    PubMed

    Gewolb, I H; Merdian, W; Warshaw, J B; Enders, A C

    1986-11-01

    In the streptozocin-induced diabetic rat, the placenta is larger and the fetus is smaller than normal. To study cellular differences that might contribute to the size and functional disparity between diabetic and control placentas, a light- and electron-microscopic analysis was performed on 14-, 18-, and 22-day (term) control and diabetic placentas. Diabetic placentas, especially later in gestation, were marked by the presence of large numbers of glycogen-distended cells in the basal zone. Within the placental labyrinth, the trophoblastic layers of the interhemal membrane were significantly thicker in the diabetic placentas on days 18 and 22, and large accumulations of liid droplets were present, especially in the inner two trophoblastic layers. In normal placentas there is a marked thinning of the placental barrier in the labyrinth by day 22 of gestation, making the thickness of the labyrinthine layers in age-matched diabetic placentas even more impressive. Finally, the labyrinth of 22-day diabetic placentas contained more glycogen and rough endoplasmic reticulum in the inner trophoblastic layer, a feature that is found in less-mature (18-day) control placentas. Thus, the diabetic placentas have a number of features that are consistent with functional immaturity/dysmaturity. Cytologic evidence confirms the presence of increased glycogen and lipid reserves in both the junctional zone and the cellular area between maternal and fetal blood.(ABSTRACT TRUNCATED AT 250 WORDS) PMID:3758495

  11. Repetitive exposure to low-dose X-irradiation attenuates testicular apoptosis in type 2 diabetic rats, likely via Akt-mediated Nrf2 activation.

    PubMed

    Zhao, Yuguang; Kong, Chuipeng; Chen, Xiao; Wang, Zhenyu; Wan, Zhiqiang; Jia, Lin; Liu, Qiuju; Wang, Yuehui; Li, Wei; Cui, Jiuwei; Han, Fujun; Cai, Lu

    2016-02-15

    To determine whether repetitive exposure to low-dose radiation (LDR) attenuates type 2 diabetes (T2DM)-induced testicular apoptotic cell death in a T2DM rat model, we examined the effects of LDR exposure on diabetic and age-matched control rats. We found that testicular apoptosis and oxidative stress levels were significantly higher in T2DM rats than in control rats. In addition, glucose metabolism-related Akt and GSK-3β function was downregulated and Akt negative regulators PTP1B and TRB3 were upregulated in the T2DM group. Superoxide dismutase (SOD) activity and catalase content were also found to be decreased in T2DM rats. These effects were partially prevented or reversed by repetitive LDR exposure. Nrf2 and its downstream genes NQO1, SOD, and catalase were significantly upregulated by repetitive exposure to LDR, suggesting that the reduction of T2DM-induced testicular apoptosis due to repetitive LDR exposure likely involves enhancement of testicular Akt-mediated glucose metabolism and anti-oxidative defense mechanisms. PMID:26704079

  12. Rats! Oh No, Not Rats!

    ERIC Educational Resources Information Center

    Strong, Gary E.

    1987-01-01

    Examples of problems encountered in a new library building--including rats and humidity--and a description of the library's collections provide a framework for this presentation of the California State Library's emergency management planning. Current preservation efforts are documented and the library's disaster and security plans are described.…

  13. Trimethyltin Modulates Reelin Expression and Endogenous Neurogenesis in the Hippocampus of Developing Rats.

    PubMed

    Toesca, Amelia; Geloso, Maria Concetta; Mongiovì, Adriana Maria; Furno, Alfredo; Schiattarella, Arcangelo; Michetti, Fabrizio; Corvino, Valentina

    2016-07-01

    Reelin is an extracellular matrix glycoprotein involved in the modulation of synaptic plasticity and essential for the proper radial migration of cortical neurons during development and for the integration and positioning of dentate granular cell progenitors; its expression is down-regulated as brain maturation is completed. Trimethyltin (TMT) is a potent neurotoxicant which causes selective neuronal death mainly localised in the CA1-CA3/hilus hippocampal regions. In the present study we analysed the expression of reelin and the modulation of endogenous neurogenesis in the postnatal rat hippocampus during TMT-induced neurodegeneration (TMT 6 mg/kg). Our results show that TMT administration induces changes in the physiological postnatal decrease of reelin expression in the hippocampus of developing rats. In particular, quantitative analysis of reelin-positive cells evidenced, in TMT-treated animals, a persistent reelin expression in the stratum lacunosum moleculare of Cornu Ammonis and in the molecular layer of Dentate Gyrus. In addition, a significant decrease in the number of bromodeoxyuridine (BrdU)-labeled newly-generated cells was also detectable in the subgranular zone of P21 TMT-treated rats compared with P21 control animals; no differences between P28 TMT-treated rats and age-matched control group were observed. In addition the neuronal commitment of BrdU-positive cells appeared reduced in P21 TMT-treated rats compared with P28 TMT-treated animals. Thus TMT treatment, administrated during development, induces an early reduction of endogenous neurogenesis and influences the hippocampal pattern of reelin expression in a temporally and regionally specific manner, altering the physiological decrease of this protein. PMID:26915108

  14. Investigation of oxidant stress and vasodepression to glyceryl trinitrate in the obese Zucker rat in vivo

    PubMed Central

    Laight, David W; Kengatharan, K M; Gopaul, Nitin K; Änggård, Erik E; Carrier, Martin J

    1998-01-01

    We examined the relationship between oxidant stress and the vasodepressor activity of glyceryl trinitrate (GTN) in vivo, including rapid GTN tolerance development, in 13-week old obese and age-matched lean Zucker rats which had been maintained for 4 weeks on either control diet or diets enriched with the lipophilic, chain-breaking antioxidants vitamin E (0.5% w w−1) or probucol (0.5% w w−1) or the superoxide anion scavenger tiron (1% w v−1 in drinking water).The basal plasma level of the isoprostane 8-epi-PGF2α, an in vivo marker of lipid peroxidation, was elevated by approximately 5 fold in the obese Zucker rat and markedly reduced by dietary lipophilic antioxidants and depressed by dietary tiron.Vasodepression to bolus does GTN (0.1–100 μg kg−1 i.v.), but not endothelium-dependent vasodepression to bolus dose acetylcholine (ACh, 0.02–2.0 μg kg−1 i.v.), was impaired in obese animals and completely restored by dietary antioxidants.Nitrate tolerance developed in vivo during a 1 h infusion of GTN (40 μg kg−1 min−1 i.v.) appeared more severe in obese animals. However, rapid nitrate tolerance was not affected by dietary antioxidants in either the obese or lean Zucker rat.We therefore provide evidence that elevated oxidant stress in the obese Zucker rat is associated with an impairment in nitrate vasodepressor activity. However, our data are not consistent with either a role for oxidant stress in rapid nitrate tolerance development in the anaesthetized Zucker rat or the aggravation of this tolerance by pre-existing oxidant stress. PMID:9831930

  15. Multimodal Highlighting of Structural Abnormalities in Diabetic Rat and Human Corneas

    PubMed Central

    Kowalczuk, Laura; Latour, Gaël; Bourges, Jean-Louis; Savoldelli, Michèle; Jeanny, Jean-Claude; Plamann, Karsten; Schanne-Klein, Marie-Claire; Behar-Cohen, Francine

    2013-01-01

    Purpose This study aimed to highlight structural corneal changes in a model of type 2 diabetes, using in vivo corneal confocal microscopy (CCM). The abnormalities were also characterized by transmission electron microscopy (TEM) and second harmonic generation (SHG) microscopy in rat and human corneas. Methods Goto-Kakizaki (GK) rats were observed at age 12 weeks (n = 3) and 1 year (n = 6), and compared to age-matched controls. After in vivo CCM examination, TEM and SHG microscopy were used to characterize the ultrastructure and the three-dimensional organization of the abnormalities. Human corneas from diabetic (n = 3) and nondiabetic (n = 3) patients were also included in the study. Results In the basal epithelium of GK rats, CCM revealed focal hyper-reflective areas, and histology showed proliferative cells with irregular basement membrane. In the anterior stroma, extracellular matrix modifications were detected by CCM and confirmed in histology. In the Descemet's membrane periphery of all the diabetic corneas, hyper-reflective deposits were highlighted using CCM and characterized as long-spacing collagen fibrils by TEM. SHG microscopy revealed these deposits with high contrast, allowing specific detection in diabetic human and rat corneas without preparation and characterization of their three-dimensional organization. Conclusion Pathologic findings were observed early in the development of diabetes in GK rats. Similar abnormalities have been found in corneas from diabetic patients. Translational Relevance This multidisciplinary study highlights diabetes-induced corneal abnormalities in an animal model, but also in diabetic donors. This could constitute a potential early marker for diagnosis of hyperglycemia-induced tissue changes. PMID:24049714

  16. Effects of hypothyroidism on vascular /sup 125/I-albumin permeation and blood flow in rats

    SciTech Connect

    Tilton, R.G.; Pugliese, G.; Chang, K.; Speedy, A.; Province, M.A.; Kilo, C.; Williamson, J.R.

    1989-05-01

    Effects of hypothyroidism on vascular 125I-albumin permeation and on blood flow were assessed in multiple tissues of male Sprague-Dawley rats rendered hypothyroid by dietary supplementation with 0.5% (wt/wt) 2-thiouracil or by thyroidectomy. In both thiouracil-treated and thyroidectomized rats, body weights, kidney weight, arterial blood pressure, and pulse rate were decreased significantly v age-matched controls. After 10 to 12 weeks of thiouracil treatment, 125I-albumin permeation was increased significantly in the kidney, aorta, eye (anterior uvea, choroid, retina), skin, and new granulation tissue, remained unchanged in brain, sciatic nerve, and heart, and was decreased in forelimb skeletal muscle. A similar pattern was observed in thyroidectomized rats, except that increases in 125I-albumin permeation for all tissues were smaller than those observed in thiouracil-treated rats, and 125I-albumin permeation in retina did not differ from controls. In both thiouracil-treated and thyroidectomized rats, changes in blood flow (assessed with 15-microns, 85Sr-labeled microspheres) relative to the decrease in arterial blood pressure were indicative of a decrease in regional vascular resistance except in the choroid and in the kidney, in which vascular resistance was increased significantly. Glomerular filtration rate was decreased, but filtration fraction and urinary excretion of albumin remained unchanged by thiouracil treatment and thyroidectomy. These results indicate that vascular hemodynamics and endothelial cell barrier functional integrity are modulated in many different tissues by the thyroid. In view of the correspondence of hypothyroid- and diabetes-induced vascular permeability changes, these results raise the possibility that altered thyroid function in diabetes may play a role in the pathogenesis of diabetic vascular disease.

  17. Daily voluntary exercise alters the cardiovascular response to hemorrhage in conscious male rats.

    PubMed

    Ahlgren, Joslyn K; Hayward, Linda F

    2011-02-24

    The present study tested the hypothesis that voluntary wheel-exercised rats would better tolerate severe hemorrhage (HEM) compared to age matched sedentary (SED) controls. Conscious rats housed with (EX, n = 8) or without (SED, n = 8) a running wheel for 6 weeks underwent a 30% total blood volume HEM over 15 min and were euthanized 90 min later and brain tissue was processed for Fos-like immunoreactivity (FLI). Both EX and SED groups displayed typical responses to HEM (initial tachycardia followed by decreased HR and MAP) but at the end of HEM, mean arterial pressure (93 ± 6 vs 58 ± 3 mm Hg) and heart rate (316 ± 17 vs. 247 ± 22 bpm,) were higher in the EX vs. SED animals and 60 min following the end of HEM, HR remained significantly elevated in the EX vs SED animals. The altered HR response to HEM in the EX animals was linked to a significant difference in sympatho-vagal drive identified by heart rate variability analysis and an augmented baroreflex response to hypotension tested in a separate group of animals (n = 4-5/group). In many of the brain regions analyzed, EX rats displayed lower levels of FLI compared to SED rats. Significantly lower levels of FLI in the EX vs SED rats were identified in the middle and caudal external lateral subnucleus of the lateral parabrachial nucleus and the dorsal cap of the hypothalamic paraventricular nucleus. These results suggest that enhanced tolerance to HEM following daily exercise may result from an EX-induced reduction in excitation or exaggerated inhibition in central circuits involved in autonomic control. PMID:21215710

  18. High-resolution mapping of a novel rat blood pressure locus on chromosome 9 to a region containing the Spp2 gene and colocalization of a QTL for bone mass.

    PubMed

    Nie, Ying; Kumarasamy, Sivarajan; Waghulde, Harshal; Cheng, Xi; Mell, Blair; Czernik, Piotr J; Lecka-Czernik, Beata; Joe, Bina

    2016-06-01

    Through linkage analysis of the Dahl salt-sensitive (S) rat and the spontaneously hypertensive rat (SHR), a blood pressure (BP) quantitative trait locus (QTL) was previously located on rat chromosome 9. Subsequent substitution mapping studies of this QTL revealed multiple BP QTLs within the originally identified logarithm of odds plot by linkage analysis. The focus of this study was on a 14.39 Mb region, the distal portion of which remained unmapped in our previous studies. High-resolution substitution mapping for a BP QTL in the setting of a high-salt diet indicated that an SHR-derived congenic segment of 787.9 kb containing the gene secreted phosphoprotein-2 (Spp2) lowered BP and urinary protein excretion. A nonsynonymous G/T polymorphism in the Spp2 gene was detected between the S and S.SHR congenic rats. A survey of 45 strains showed that the T allele was rare, being detected only in some substrains of SHR and WKY. Protein modeling prediction through SWISSPROT indicated that the predicted protein product of this variant was significantly altered. Importantly, in addition to improved cardiovascular and renal function, high salt-fed congenic animals carrying the SHR T variant of Spp2 had significantly lower bone mass and altered bone microarchitecture. Total bone volume and volume of trabecular bone, cortical thickness, and degree of mineralization of cortical bone were all significantly reduced in congenic rats. Our study points to opposing effects of a congenic segment containing the prioritized candidate gene Spp2 on BP and bone mass. PMID:27113531

  19. Age and gender differences in excitation-contraction coupling of the rat ventricle

    PubMed Central

    Leblanc, Normand; Chartier, Denis; Gosselin, Hugues; Rouleau, Jean-Lucien

    1998-01-01

    The objective of this study was to determine potential post-pubertal gender-specific differences in the contractility of papillary muscles, the electrophysiological properties and Ca2+ transients of freshly dissociated ventricular myocytes from the rat heart. The contractions of rat papillary muscles from 2- to 14-month-old male and female rats were studied under isometric and isotonic conditions (29 °C). While the hearts of young (2–4 months) male and female rats displayed a similar contractile profile, papillary muscles of female rats aged 6 months and older exhibited smaller isometric and isotonic contractions, smaller maximal rates of tension and shortening development and decline (±DT/dt and ±DL/dt) velocities during both the onset and relaxation phases, and shorter contractions than age-matched males. To explore the possible cellular basis accounting for these differences, action potentials and macroscopic currents were recorded from freshly dissociated myocytes using the whole-cell patch clamp technique (35 °C). Action potentials from male and female myocytes of 3- and 9-month-old rats did not vary as a function of age or gender. Consistent with these results, the magnitude (expressed in pA pF−1), voltage-dependence and kinetics of the inward rectifier (IK1), transient outward (Ito) and sustained (IK) K+ currents displayed little, if any dependence on age or gender. L-type Ca2+ current (ICa(L)) measured in caesium-loaded myocytes (35 °C) from male and female rats of 3, 6 and 9 months of age exhibited similar characteristics. In contrast, while Ca2+ transients measured with indo-1 were similar between 3-month-old male and female rat myocytes, Ca2+ transients of 10-month-old female myocytes were significantly reduced and showed a diminished rate of relaxation in comparison with those recorded in male rats of similar age. These results suggest that important gender-related changes in excitation-contraction coupling occur following puberty, probably due

  20. Intermittent ethanol consumption depresses endocannabinoid-signaling in the dorsolateral striatum of rat.

    PubMed

    Adermark, Louise; Jonsson, Susanne; Ericson, Mia; Söderpalm, Bo

    2011-12-01

    Recent research suggests that adaptations elicited by drugs of abuse share common features with traditional learning models, and that drugs of abuse cause long-term changes in behavior by altering synaptic function and plasticity. In this study, endocannabinoid (eCB) signaling in the dorsolateral striatum, a brain region vital for habit formation, was evaluated in acutely isolated brain slices from ethanol (EtOH)-consuming rats and control rats. EtOH-consuming rats had free access to a 20% EtOH solution for three 24 hour sessions a week during seven weeks and consumed an average of 3.4 g/kg per session. eCB-mediated long-lasting disinhibition (DLL) of population spike (PS) amplitude induced by moderate frequency stimulation was impaired in EtOH-consuming rats, and was not restored by the muscarinic receptor antagonist scopolamine (10 μM). The lack of DLL could be linked to a reduced GABA(A) receptor tone, since bicuculline-mediated disinhibition of striatal output was significantly reduced in slices from EtOH-consuming rats. However, eCB signaling induced by high frequency stimulation (HFS) was also impaired in slices from EtOH-consuming rats and isolated control rats. Activation of presynaptic cannabinoid 1 receptors (CB1R) with WIN55,212-2 (250 nM, 1 μM) significantly modulated PS amplitude in slices from age-matched control rats while slices from EtOH-consuming rats remained unaffected, indicating that eCB signaling is inhibited at a level that is downstream from CB1R activation. Intermittent alcohol intake for seven weeks might thus be sufficient to modulate a presynaptic mechanism that needs to be synergized with CB1R activation for induction of long-term depression (LTD). In conclusion, alcohol consumption inhibits striatal eCB signaling in a way that could be of importance for understanding the neurological underpinnings of addictive behavior. PMID:21251919

  1. Alterations in Glutathione Redox Metabolism, Oxidative Stress, and Mitochondrial Function in the Left Ventricle of Elderly Zucker Diabetic Fatty Rat Heart

    PubMed Central

    Raza, Haider; John, Annie; Howarth, Frank C.

    2012-01-01

    The Zucker diabetic fatty (ZDF) rat is a genetic model in which the homozygous (FA/FA) male animals develop obesity and type 2 diabetes. Morbidity and mortality from cardiovascular complications, due to increased oxidative stress and inflammatory signals, are the hallmarks of type 2 diabetes. The precise molecular mechanism of contractile dysfunction and disease progression remains to be clarified. Therefore, we have investigated molecular and metabolic targets in male ZDF (30–34 weeks old) rat heart compared to age matched Zucker lean (ZL) controls. Hyperglycemia was confirmed by a 4-fold elevation in non-fasting blood glucose (478.43 ± 29.22 mg/dL in ZDF vs. 108.22 ± 2.52 mg/dL in ZL rats). An increase in reactive oxygen species production, lipid peroxidation and oxidative protein carbonylation was observed in ZDF rats. A significant increase in CYP4502E1 activity accompanied by increased protein expression was also observed in diabetic rat heart. Increased expression of other oxidative stress marker proteins, HO-1 and iNOS was also observed. GSH concentration and activities of GSH-dependent enzymes, glutathione S-transferase and GSH reductase, were, however, significantly increased in ZDF heart tissue suggesting a compensatory defense mechanism. The activities of mitochondrial respiratory enzymes, Complex I and Complex IV were significantly reduced in the heart ventricle of ZDF rats in comparison to ZL rats. Western blot analysis has also suggested a decreased expression of IκB-α and phosphorylated-JNK in diabetic heart tissue. Our results have suggested that mitochondrial dysfunction and increased oxidative stress in ZDF rats might be associated, at least in part, with altered NF-κB/JNK dependent redox cell signaling. These results might have implications in the elucidation of the mechanism of disease progression and designing strategies for diabetes prevention. PMID:23203193

  2. Spaceflight effects on biomechanical and biochemical properties of rat vertebrae

    NASA Technical Reports Server (NTRS)

    Zernicke, R. F.; Vailas, A. C.; Grindeland, R. E.; Kaplansky, A.; Salem, G. J.; Martinez, D. A.

    1990-01-01

    The biomechanical and biochemical responses of lumbar vertebral bodies during a 12.5-day spaceflight (Cosmos 1887 biosatellite) were determined for rapidly growing rats (90-day-old, Czechoslovakian-Wistar). By use of age-matched vivarium controls (normal cage environment) and synchronous controls (simulated flight conditions), as well as a basal control group (killed before lift-off on the 1st day of flight), the combined influences of growth and space-flight could be examined. Centra of the sixth lumbar vertebrae (L6) were compressed to 50% strain at a fast strain rate while immersed in physiological buffer (37 degrees C). The body masses of vivarium and synchronous controls were significantly heavier than either the flight or basal controls. The flight group had an L6 vertebral body compressional stiffness that was 39% less than the vivarium controls, 47% less than the synchronous control, and 16% less than the basal controls. In addition, the average initial maximum load of the flight L6 was 22% less than vivarium controls and 18% less than the synchronous controls, whereas the linear compressional load of the flight group averaged 34% less than the vivarium and 25% less than the synchronous groups. The structural properties of the vertebrae from the 12.5-day-younger basal group closely resembled the flight vertebrae. Calcium, phosphorous, and hydroxyproline concentrations were not significantly different among the groups. Nevertheless, the lack of strength and stiffness development in spaceflight, coupled with a smaller proportion of mature hydroxypyridinoline cross-links, suggested that the 12.5 days of spaceflight slowed the maturation of trabecular bone in the vertebral bodies of rapidly growing rats.

  3. Perirhinal Cortex Hyperexcitability in Pilocarpine-Treated Epileptic Rats

    PubMed Central

    Benini, Ruba; Longo, Daniela; Biagini, Giuseppe; Avoli, Massimo

    2016-01-01

    The perirhinal cortex (PC), which is heavily connected with several epileptogenic regions of the limbic system such as the entorhinal cortex and amygdala, is involved in the generation and spread of seizures. However, the functional alterations occurring within an epileptic PC network are unknown. Here, we analyzed this issue by using in vitro electrophysiology and immunohistochemistry in brain tissue obtained from pilocarpine-treated epileptic rats and age-matched, nonepileptic controls (NECs). Neurons recorded intracellularly from the PC deep layers in the two experimental groups had similar intrinsic and firing properties and generated spontaneous depolarizing and hyperpolarizing postsynaptic potentials with comparable duration and amplitude. However, spontaneous and stimulus-induced epileptiform discharges were seen with field potential recordings in over one-fifth of pilocarpine-treated slices but never in NEC tissue. These network events were reduced in duration by antagonizing NMDA receptors and abolished by NMDA + non-NMDA glutamatergic receptor antagonists. Pharmacologically isolated isolated inhibitory postsynaptic potentials had reversal potentials for the early GABAA receptor-mediated component that were significantly more depolarized in pilocarpine-treated cells. Experiments with a potassium-chloride cotransporter 2 antibody identified, in pilocarpine-treated PC, a significant immunostaining decrease that could not be explained by neuronal loss. However, interneurons expressing parvalbumin and neuropeptide Y were found to be decreased throughout the PC, whereas cholecystokinin-positive cells were diminished in superficial layers. These findings demonstrate synaptic hyper-excitability that is contributed by attenuated inhibition in the PC of pilocarpine-treated epileptic rats and underscore the role of PC networks in temporal lobe epilepsy. PMID:20865722

  4. Investigating the Role of Hippocampal BDNF in Anxiety Vulnerability Using Classical Eyeblink Conditioning

    PubMed Central

    Janke, Kellie L.; Cominski, Tara P.; Kuzhikandathil, Eldo V.; Servatius, Richard J.; Pang, Kevin C. H.

    2015-01-01

    Dysregulation of brain-derived neurotrophic factor (BDNF), behavioral inhibition temperament (BI), and small hippocampal volume have been linked to anxiety disorders. Individuals with BI show facilitated acquisition of the classically conditioned eyeblink response (CCER) as compared to non-BI individuals, and a similar pattern is seen in an animal model of BI, the Wistar-Kyoto (WKY) rat. The present study examined the role of hippocampal BDNF in the facilitated delay CCER of WKY rats. Consistent with earlier work, acquisition was facilitated in WKY rats compared to the Sprague Dawley (SD) rats. Facilitated acquisition was associated with increased BDNF, TrkB, and Arc mRNA in the dentate gyrus of SD rats, but learning-induced increases in BDNF and Arc mRNA were significantly smaller in WKY rats. To determine whether reduced hippocampal BDNF in WKY rats was a contributing factor for their facilitated CCER, BDNF or saline infusions were given bilaterally into the dentate gyrus region 1 h prior to training. BDNF infusion did not alter the acquisition of SD rats, but significantly dampened the acquisition of CCER in the WKY rats, such that acquisition was similar to SD rats. Together, these results suggest that inherent differences in the BDNF system play a critical role in the facilitated associative learning exhibited by WKY rats, and potentially individuals with BI. Facilitated associative learning may represent a vulnerability factor in the development of anxiety disorders. PMID:26257661

  5. Enhancement of Amygdaloid Neuronal Dendritic Arborization by Fresh Leaf Juice of Centella asiatica (Linn) During Growth Spurt Period in Rats

    PubMed Central

    Muddanna Rao, S.; Gurumadhva Rao, S.

    2009-01-01

    Centella asiatica (CeA) is a creeping herb, growing in moist places in India and other Asian Countries. Ayurvedic system of medicine, an alternate system of medicine in India, uses leaves of CeA for memory enhancement. Here, we have investigated the role of CeA fresh leaf juice treatment during growth spurt period of rats on dendritic morphology of amygdaloid neurons, one of the regions concerned with learning and memory. The present study was conducted on neonatal rat pups. The rat pups (7-days-old) were fed with 2, 4 and 6 ml/kg body of fresh leaf juice of CeA for 2, 4 and 6 weeks. After the treatment period, the rats were killed, brains removed and amygdaloid neurons impregnated with Silver nitrate (Golgi staining). Amygdaloid neurons were traced using camera lucida and dendritic branching points (a measure of dendritic arborization) and intersections (a measure dendritic length) quantified. These data were compared with those of age-matched control rats. The results showed a significant increase in dendritic length (intersections) and dendritic branching points along the length of dendrites of the amygdaloid neurons of rats treated with 4 and 6 ml/kg body weight/day of CeA for longer periods of time (i.e. 4 and 6 weeks). We conclude that constituents/active principles present in CeA fresh leaf juice has neuronal dendritic growth stimulating property; hence it can be used for enhancing neuronal dendrites in stress and other neurodegenerative and memory disorders. PMID:18955230

  6. Improved Leptin Sensitivity as a Potential Candidate Responsible for the Spontaneous Food Restriction of the Lou/C Rat

    PubMed Central

    Veyrat-Durebex, Christelle; Poher, Anne-Laure; Caillon, Aurélie; Somm, Emmanuel; Vallet, Philippe; Charnay, Yves; Rohner-Jeanrenaud, Françoise

    2013-01-01

    The Lou/C rat, an inbred strain of Wistar origin, was described as a model of resistance to age- and diet-induced obesity. Although such a resistance involves many metabolic parameters described in our previous studies, Lou/C rats also exhibit a spontaneous food restriction due to decreased food consumption during the nocturnal period. We then attempted to delineate the leptin sensitivity and mechanisms implicated in this strain, using different protocols of acute central and peripheral leptin administration. A first analysis of the meal patterns revealed that Lou/C rats eat smaller meals, without any change in meal number compared to age-matched Wistar animals. Although the expression of the recognized leptin transporters (leptin receptors and megalin) measured in the choroid plexus was normal in Lou/C rats, the decreased triglyceridemia observed in these animals is compatible with an increased leptin transport across the blood brain barrier. Improved hypothalamic leptin signaling in Lou/C rats was also suggested by the higher pSTAT3/STAT3 (signal transducer and activator of transcription 3) ratio observed following acute peripheral leptin administration, as well as by the lower hypothalamic mRNA expression of the suppressor of cytokine signaling 3 (SOCS3), known to downregulate leptin signaling. To conclude, spontaneous hypophagia of Lou/C rats appears to be related to improved leptin sensitivity. The main mechanism underlying such a phenomenon consists in improved leptin signaling through the Ob-Rb leptin receptor isoform, which seems to consequently lead to overexpression of brain-derived neurotrophic factor (BDNF) and thyrotropin-releasing hormone (TRH). PMID:24039946

  7. Cellular Inflammatory Infiltrate in Pneumonitis Induced by a Single Moderate Dose of Thoracic X Radiation in Rats

    PubMed Central

    Szabo, Sara; Ghosh, Swarajit N.; Fish, Brian L.; Bodiga, Sreedhar; Tomic, Rade; Kumar, Gagan; Morrow, Natalya V.; Moulder, John E.; Jacobs, Elizabeth R.; Medhora, Meetha

    2010-01-01

    The goal of these studies was to characterize the infiltrating inflammatory cells during pneumonitis caused by moderate doses of radiation. Two groups of male rats (WAG/RijCmcr, 8 weeks old) were treated with single 10- or 15-Gy doses of thoracic X radiation; a third group of age-matched animals served as controls. Only 25% rats survived the 15-Gy dose. Bronchoalveolar lavage fluid and whole lung mounts were subjected to cytological and histological evaluation after 8 weeks for distribution of resident macrophages, neutrophils, lymphocytes and mast cells. There was a modest increase in airway and airspace-associated neutrophils in lungs from rats receiving 15 Gy. Mast cells (detected by immunohistochemistry for tryptase) increased over 70% with 10 Gy and over 13-fold after 15 Gy, with considerable leakage of tryptase into blood vessels and airways. Circulating levels of eight inflammatory cytokines were not altered after 10 Gy but appeared to decrease after 15 Gy. In summary, there were only modest increases in cellular inflammatory infiltrate during pneumonitis after a non-lethal dose of 10 Gy, but there was a dramatic rise in mast cell infiltration after 15 Gy, suggesting that circulating levels of mast cell products may be useful markers of severe pneumonitis. PMID:20334527

  8. Changes in Nitrergic and Tachykininergic Pathways in Rat Proximal Colon In Response to Chronic Treatment With Otilonium Bromide

    PubMed Central

    Cipriani, Gianluca; Gibbons, Simon J.; Arumugam, Saravanaperumal Siva; Malysz, John; Sha, Lei; Szurszewski, Joseph H.; Linden, David R.; Evangelista, Stefano; Faussone-Pellegrini, Maria Simonetta; Vannucchi, Maria Giuliana; Farrugia, Gianrico

    2015-01-01

    Background Otilonium bromide (OB) is used as a spasmolytic in the treatment of the functional bowel disorder irritable bowel syndrome. Although its acute effects on colonic relaxation are well-characterized, little is known about the effects of chronic administration of OB on enteric neurons, neuromuscular transmission, and interstitial cells of Cajal (ICC), key regulators of the gut function. Methods Adult Sprague-Dawley rats were treated with OB in drinking water at a dose of 2 mg/kg for 30 days. The colons of OB-treated and age-matched control rats were studied by confocal immunohistochemistry to detect immunoreactivity (IR) in myenteric plexus neurons for nitrergic and tachykininergic markers, and also by microelectrode electrophysiology. Results Using immunohistochemistry, chronic OB administration did not change total neuron number, assessed by anti-Hu IR, but resulted in a significant increase in NK1 receptor positive neurons, a decrease in neuronal nitric oxide synthase (nNOS) expressing neurons, and a reduction in volume of substance P in nerve fibers in the myenteric plexus. Chronic OB administration potentiated inhibitory and excitatory junction potentials evoked by repetitive electrical field stimulation. The various types of colonic ICC, detected by Kit IR, were not altered nor were slow waves or smooth muscle membrane potential. Conclusions and Inferences Chronic treatment with OB caused significant changes in the nitrergic and tachykinergic components of the myenteric plexus and in both inhibitory and excitatory neurotransmission in the rat colon. PMID:25930994

  9. Relations between contractile responses and. beta. -adrenoceptors in gastric fundus of diabetic rats

    SciTech Connect

    Sakai, Yasushi; Inazu, Masato; Aihara, Kazuo; Inoue, Kazuaki; Homma, Ikuo )

    1991-01-01

    Contractile responses to norepinephrine (NE), and the population of {beta}-adrenoceptors, were determined in gastric fundus smooth muscle from rats with diabetes induced by streptozotocin(STZ), and age-matched controls. Relaxation and/or contraction of fundus strips of controls and diabetics were induced by 10{sup {minus}5}M NE. Responses to NE were mainly relaxation in gastric fundus isolated from controls, and contraction in fundus isolated from diabetics. Contraction was blocked by 10{sup {minus}8}M prazosin and relaxation was blocked by 10{sup {minus}6}M propranolol. Relaxation by isoproterenol of contraction induced by 10{sup {minus}6}M acetylcholine was significantly less in fundus from diabetics than in that from controls. The number of {beta}-adrenoceptors, measured with ({sup 125}I)iodocyanopindorol as a ligand, was significantly less in gastic fundus membrane isolated from diabetics than in that from controls, but affinity was no different. The level of plasma catecholamine was higher in diabetics than in controls. Results suggest that depression of gastric fundus relaxation and increase of contraction by NE in diabetics could be due to fewer {beta}-adrenoceptor binding sites caused by down-regulation by higher catecholamine level in diabetic rats.

  10. Temporal Evaluation of Cardiac Myocyte Hypertrophy and Hyperplasia in Male Rats Secondary to Chronic Volume Overload

    PubMed Central

    Du, Yan; Plante, Eric; Janicki, Joseph S.; Brower, Gregory L.

    2010-01-01

    The temporal myocardial remodeling induced by chronic ventricular volume overload in male rats was examined. Specifically, left ventricular (LV) cardiomyocyte length and width, sarcomere length, and number of nuclei were measured in male rats (n = 8 to 17) at 1, 3, 5, 7, 21, 35, and 56 days after creation of an infrarenal aortocaval fistula. In contrast to previously published reports of progressive increases in cardiomyocyte length and cross-sectional area at 5 days post-fistula and beyond in female hearts, cardiomyocyte length and width did not increase significantly in males during the first 35 days of volume overload. Furthermore, a significant decrease in cardiomyocyte length relative to age-matched controls, together with a reduced number of sarcomeres per cell, was noted in male hearts at 5 days post-fistula. There was a concurrent increase in the percentage of mononucleated cardiomyocytes from 11.6% to 18% at 5 days post-fistula. These initial differences could not be attributed to cardiomyocyte proliferation, and treatment with a microtubule stabilizing agent prevented them from occurring. The subsequent significant increase in LV weight without corresponding increases in cardiomyocyte dimensions is indicative of hyperplasia. Thus, these findings indicate hyperplasia resulting from cytokinesis of cardiomyocytes is a key mechanism, independent of hypertrophy, that contributes to the significant increase in LV mass in male hearts subjected to chronic volume overload. PMID:20651227

  11. Intracranial electrode implantation produces regional neuroinflammation and memory deficits in rats

    SciTech Connect

    Kuttner-Hirshler, Y.; Biegon, A.; Kuttner-Hirshler, Y.; Polat, U.; Biegon, A.

    2009-12-21

    Deep brain stimulation (DBS) is an established treatment for advanced Parkinson's disease (PD). The procedure entails intracranial implantation of an electrode in a specific brain structure followed by chronic stimulation. Although the beneficial effects of DBS on motor symptoms in PD are well known, it is often accompanied by cognitive impairments, the origin of which is not fully understood. To explore the possible contribution of the surgical procedure itself, we studied the effect of electrode implantation in the subthalamic nucleus (STN) on regional neuroinflammation and memory function in rats implanted bilaterally with stainless steel electrodes. Age-matched sham and intact rats were used as controls. Brains were removed 1 or 8 weeks post-implantation and processed for in vitro autoradiography with [(3)H]PK11195, an established marker of microglial activation. Memory function was assessed by the novel object recognition test (ORT) before surgery and 2 and 8 weeks after surgery. Electrode implantation produced region-dependent changes in ligand binding density in the implanted brains at 1 as well as 8 weeks post-implantation. Cortical regions showed more intense and widespread neuroinflammation than striatal or thalamic structures. Furthermore, implanted animals showed deficits in ORT performance 2 and 8 weeks post-implantation. Thus, electrode implantation resulted in a widespread and persistent neuroinflammation and sustained memory impairment. These results suggest that the insertion and continued presence of electrodes in the brain, even without stimulation, may lead to inflammation-mediated cognitive deficits in susceptible individuals, as observed in patients treated with DBS.

  12. Stem cell therapy restores viscoelastic properties of myocardium in rat model of hypertension.

    PubMed

    Rubiano, Andres; Qi, Yanfei; Guzzo, Dominic; Rowe, Kyle; Pepine, Carl; Simmons, Chelsey

    2016-06-01

    Extensive remodeling of the myocardium is seen in a variety of cardiovascular diseases, including systemic hypertension. Stem cell therapy has been proposed to improve the clinical outcomes of hypertension, and we hypothesized that changes in mechanical properties of the myocardium would accompany the progression of disease and the results of treatment conditions. Using spontaneously hypertensive rats (SHR) as a model of hypertension, we treated 13-week-old hypertensive rats with a single injection of adipose-derived stem cells (ADSC) isolated from a normotensive control. We indented the isolated ventricles of control, untreated sham-injected SHR, and ADSC-treated SHR hearts with a custom cantilever-based system and fit the resulting data to a standard linear solid model. SHR animals had higher blood pressure (198.4±25.9mmHg) and lower ejection fraction (69.9±4.2%) than age-matched control animals (109.0±1.6mmHg, 88.2±1.3%), and increased viscoelastic properties accompanied these clinical changes (right ventricle effective stiffness, SHR: 21.97±5.10kPa, Control: 13.14±3.48kPa). ADSC-treated animals saw improvement in clinical parameters compared to the untreated SHR group, which was also accompanied by a significant restoration of viscoelastic properties of the myocardium (ACSD-treated SHR: 9.77±6.96kPa). PMID:26748260

  13. Beneficial effects of ethanol extracts of Red Liriope platyphylla on vascular dysfunction in the aorta of spontaneously hypertensive rats

    PubMed Central

    Lee, Young-Ju; Koh, Eun-Kyoung; Kim, Ji-Eun; Go, Jun; Song, Sung-Hwa; Seong, Ji-Eun; Son, Hong-Joo; Kang, Byeong-Cheol

    2015-01-01

    Some biological effects of Red Liriope platyphylla (RLP) on various chronic diseases including Alzheimer's disease, diabetes and obesity were suggested after a report of the production from Liriope platyphylla (L. platyphylla, LP) roots using a steaming process. To examine the beneficial effects of ethanol extracts RLP (EEtRLP) on the vascular dysfunction of hypertension, alterations in key factors related to vascular regulation and antioxidant conditions were investigated in spontaneously hypertensive rats (SHR) after EEtRLP treatment for 2 weeks. High levels of 2,2-diphenyl-1-picrylhydrazyl (DPPH) scavenging activity were detected in 500 or 1,000 mg/mL EEtRLP. Although no significant improvement of systolic blood pressure or aortic wall thickness were observed in the EEtRLP treated group, the expression level of angiotensin converting enzyme (ACE) and ACE2 increased significantly after EEtRLP treatment. Moreover, the concentration of aldosterone and K ion in serum rapidly recovered in the EEtRLP treated group relative to the vehicle treated group. Furthermore, the endothelial nitric oxide synthase (eNOS) expression and superoxide dismutase (SOD) activity were significantly increased in the EEtRLP treated group relative to the vehicle treated group, while the level of malondialdehyde (MDA) and NOx in the serum of the same group were recovered to the level of Wistar Kyoto (WKY) rats. Overall, the results presented herein provide novel evidence that EEtRLP treatment may improve vascular dysfunction in the aorta of the SHR through up regulation of the antioxidant state and down regulation of aldosterone and K ion concentration. These results also suggest that EEtRLP may be a potential candidate for treatment of various chronic diseases showing vascular dysfunction. PMID:25806079

  14. Role of PKCδ in Enhanced Expression of Gqα/PLCβ1 Proteins and VSMC Hypertrophy in Spontaneously Hypertensive Rats

    PubMed Central

    Atef, Mohammed Emehdi; Anand-Srivastava, Madhu B.

    2016-01-01

    Gqα signaling has been implicated in cardiac hypertrophy. In addition, angiotensin II (Ang II) was also shown to induce its hypertrophic effect through Gqα and PKCδ activation. We recently showed the role of enhanced expression of Gqα/PLCβ1 proteins in vascular smooth muscle cell (VSMC) hypertrophy, however, the role of PKCδ in VSMC hypertrophy in animal model is still lacking. The present study was therefore undertaken to examine the role of PKCδ and the associated signaling mechanisms in VSMC hypertrophy using 16-week-old spontaneously hypertensive rats (SHR). VSMC from 16-week-old SHR exhibited enhanced phosphorylation of PKCδ-Tyr311 and increased protein synthesis, marker of hypertrophy, as compared to WKY rats which was attenuated by rottlerin, an inhibitor of PKCδ. In addition, knocking down of PKCδ by PKCδ-siRNA also attenuated enhanced protein synthesis in VSMC from SHR. Furthermore, rottlerin attenuated the increased production of superoxide anion, NAD(P)H oxidase activity, increased expression of Gqα, phospholipase C (PLC)β1, insulin like growth factor-1 receptor (IGF-1R) and epidermal growth factor receptor (EGFR) proteins in VSMC from SHR. In addition, the enhanced phosphorylation of c-Src, PKCδ-Tyr311, IGF-1R, EGFR and ERK1/2 exhibited by VSMC from SHR was also attenuated by rottlerin. These results suggest that VSMC from SHR exhibit enhanced activity of PKCδ and that PKCδ is the upstream molecule of reactive oxygen species (ROS) and contributes to the enhanced expression of Gqα and PLCβ1 proteins and resultant VSMC hypertrophy involving c-Src, growth factor receptor transactivation and MAP kinase signaling. PMID:27379421

  15. Cadmium intake and systemic exposure in postmenopausal women and age-matched men who smoke cigarettes.

    PubMed

    Ebert-McNeill, Andrea; Clark, Sara P; Miller, James J; Birdsall, Paige; Chandar, Manisha; Wu, Lucia; Cerny, Elizabeth A; Hall, Patricia H; Johnson, Maribeth H; Isales, Carlos; Chutkan, Norman; Bhattacharyya, Maryka H

    2012-11-01

    Mean blood cadmium (B-Cd) concentrations are two- to threefold higher in smokers than in nonsmokers. The basis for this phenomenon is not well understood. We conducted a detailed, multifaceted study of cadmium exposure in smokers. Groups were older smokers (62±4 years, n = 25, 20% male) and nonsmokers (62±3 years, n = 16, 31% male). Each subject's cigarettes were machine smoked, generating individually paired measures of inhaled cadmium (I-Cd) versus B-Cd; I-Cd and B-Cd were each evaluated three times, at monthly intervals. Urine cadmium (U-Cd) was analyzed for comparison. In four smokers, a duplicate-diet study was conducted, along with a kinetic study of plasma cadmium versus B-Cd. Female smokers had a mean B-Cd of 1.21ng Cd/ml, with a nearly 10-fold range (0.29-2.74ng Cd/ml); nonsmokers had a lower mean B-Cd, 0.35ng Cd/ml (p < 0.05), and narrower range (0.20-0.61ng Cd/ml). Means and ranges for males were similar. Estimates of cadmium amounts inhaled daily for our subjects smoking ≥ 20 cigarettes/day were far less than the 15 µg Cd reported to be ingested daily via diet. This I-Cd amount was too low to alone explain the 3.5-fold elevation of B-Cd in our smokers, even assuming greater cadmium absorption via lungs than gastrointestinal tract; cadmium accumulated in smokers' lungs may provide the added cadmium. Finally, B-Cd appeared to be linearly related to I-Cd values in 75% of smokers, whereas 25% had far higher B-Cd, implying a possible heterogeneity among smokers regarding circulating cadmium concentrations and potentially cadmium toxicity. PMID:22831969

  16. Neural Mechanisms of Verb Argument Structure Processing in Agrammatic Aphasic and Healthy Age-Matched Listeners

    ERIC Educational Resources Information Center

    Thompson, Cynthia K.; Bonakdarpour, Borna; Fix, Stephen F.

    2010-01-01

    Processing of lexical verbs involves automatic access to argument structure entries entailed within the verb's representation. Recent neuroimaging studies with young normal listeners suggest that this involves bilateral posterior peri-sylvian tissue, with graded activation in these regions on the basis of argument structure complexity. The aim of…

  17. Cadmium affects the episodic luteinizing hormone secretion in male rats: possible age-dependent effects.

    PubMed

    Lafuente, A; Márquez, N; Piquero, S; Esquifino, A I

    1999-01-11

    Cadmium affects luteinizing hormone (LH) secretion through unknown mechanisms. The present study was undertaken to assess whether chronic exposure to low concentrations of cadmium may affect the episodic secretion of LH and if these effects are age-dependent. Male rats were given cadmium at a dose of 50 ppm in the drinking water, from day 30 to 60 or from day 60 to 90 of life. Age-matched rats with access to cadmium-free water were used as controls. At the end of the treatment, blood samples were collected every 7 min for 3 h, from 10:30 to 13.30 in conscious, freely moving rats. In control animals, mean serum LH levels and pulse duration increased with age (P < or = 0.001), and pulse frequency and the relative amplitude of LH pulses decreased (P < or = 0.001). Cadmium administration, from day 30 to 60 of life, decreased the pulse frequency and mean half-life of the hormone (P < or = 0.05, P < or = 0.01, respectively). However, no changes in any other parameters studied were observed as compared to the control group. When cadmium was administered from day 60 to 90, mean serum LH levels and the duration of LH pulses decreased (P < or = 0.05), whereas the pulse frequency increased (P < or = 0.05). The absolute and relative amplitude of the LH peaks and the mean half-life of the hormone were not changed after cadmium administration from day 60 to 90. These results indicate that low doses of cadmium change the pulsatile secretion of LH in male rats and that the effect of cadmium on episodic LH release was age-dependent. PMID:10048746

  18. Imaging radiation pneumonitis in a rat model of a radiological terrorism incident

    NASA Astrophysics Data System (ADS)

    Molthen, Robert; Wu, QingPing; Krenz, Gary; Medhora, Meetha; Jacobs, Elizabeth; Moulder, John E.

    2009-02-01

    We have developed a rat model of single, sub-lethal thoracic irradiation. Our irradiation protocol is considered representative of exposures near the detonation site of a dirty bomb or small nuclear device. The model is being used to investigate techniques for identifying, triaging and treating possible victims. In addition to physiological markers of right ventricular hypertrophy, pulmonary vascular resistance, and arterial distensibility, we present two methods for quantifying microvascular density. We used methods including microfocal X-ray imaging to investigate changes in lung structure/function resulting from radiation exposure. Radiation pneumonitis is a complication in subjects receiving thoracic irradiation. A radiographic hallmark of acute radiation pneumonitis is a diffuse infiltrate corresponding to the radiation treatment field. We describe two methods for quantifying small artery dropout that occurs in the model at the same time-period. Rats were examined 3-days, 2-weeks, 1-month (m), 2-m, 5-m, and 12-m post-irradiation and compared with aged-matched controls. Right ventricular hypertrophy and increases in pulmonary vascular resistance were present during the pneumonitis phase. Vascular injury was dependent on dose and post-irradiation duration. Rats irradiated with 5 Gy had few detectable changes, whereas 10 Gy resulted in a significant decrease in both microvascular density and arterial distensibility around 2- m, the decrease in each lessening, but extending through 12-m. In conclusion, rats irradiated with a 10 Gy dose had changes in vascular structure concurrent with the onset of radiation pneumonitis that were detectable with our imaging techniques and these structural changes persist after resolution of the pneumonitis.

  19. Increased activity of tyrosine hydroxylase in the cerebellum of the x-irradiated dystonic rat

    SciTech Connect

    Dopico, A.M.; Rios, H.; Mayo, J.; Zieher, L.M. )

    1990-08-01

    The exposure of the cephalic end of rats to repeated doses of x-irradiation (150 rad) immediately after birth induces a long-term increase in the noradrenaline (NA) content of cerebellum (CE) (+ 37.8%), and a decrease in cerebellar weight (65.2% of controls), which results in an increased NA concentration (+ 109%). This increase in the neurotransmitter level is accompanied by a dystonic syndrome and histological abnormalities: Purkinje cells (the target cells for NA afferents to CE) fail to arrange in a characteristic monolayer, and their primary dendritic tree appears randomly oriented. The injection of reserpine 0.9 and 1.2 mg/kg ip to adult rats for 18 h depletes cerebellar NA content in both controls (15.7 {plus minus} 4 ng/CE and 2.8 {plus minus} 1.5 ng/CE, respectively) and x-irradiated rats (17.1 {plus minus} 1 ng/CE and 8.3 {plus minus} 2 ng/CE, respectively). The activity of tyrosine hydroxylase (TH) in CE of adult rats, measured by an in vitro assay, is significantly increased in neonatally x-irradiated animals when compared to age-matched controls (16.4 {plus minus} 1.4 vs 6.32 {plus minus} 0.6 nmol CO2/h/mg prot., p less than 0.01). As observed for NA levels, a net increase in TH activity induced by the ionizing radiation is also measured: 308.9 {plus minus} 23.8 vs 408.2 {plus minus} 21.5 nmol CO2/h/CE, p less than 0.01 (controls and x-treated, respectively). These results suggest that x-irradiation at birth may induce an abnormal sprouting of noradrenergic afferents to CE. The possibility that these changes represent a response of the NA system to the dystonic syndrome is discussed.

  20. Differential Effects of Radiation and Age on Diffusion Tensor Imaging in Rats

    PubMed Central

    Peiffer, Ann M; Shi, Lei; Olson, John; Brunso-Bechtold, Judy K

    2010-01-01

    Greater than 50% of adults and ∼100% of children who survive >6 months after fractionated partial or whole-brain radiotherapy develop cognitive impairments. Noninvasive methods are needed for detecting and tracking the radiation-induced brain injury associated with these impairments. Using magnetic resonance imaging, we sought to detect structural changes associated with brain injury in our rodent model of fractionated whole-brain irradiation (fWBI) induced cognitive impairment and to compare those changes with alterations that occur during the aging process. Middle aged rats were given a clinically relevant dose of fWBI (40 Gy: two 5 Gy fractions/wk for 4 wk) and scanned approximately one year post-irradiation to obtain whole-brain T2 and diffusion tensor images (DTI); control groups of sham-irradiated age-matched and young rats were also scanned. No gross structural changes were evident in the T2 structural images, and no detectable fWBI-induced DTI changes in fractional anisotropy (FA) were found in heavily myelinated white matter (corpus callosum, cingulum, and deep cortical white matter). However, significant fWBI-induced variability in FA distribution was present in the superficial parietal cortex due to an fWBI-induced decline in FA in the more anterior slices through parietal cortex. Young rats had significantly lower FA values relative to both groups of older rats, but only within the corpus callosum. These findings suggest that targets of the fWBI-induced change in this model may be the less myelinated or unmyelinated axons, extracellular matrix, or synaptic fields rather than heavily myelinated tracts. PMID:20599817

  1. Marine omega-3 polyunsaturated fatty acids induce sex-specific changes in reinforcer-controlled behaviour and neurotransmitter metabolism in a spontaneously hypertensive rat model of ADHD

    PubMed Central

    2012-01-01

    Background Previous reports suggest that omega-3 (n-3) polyunsaturated fatty acids (PUFA) supplements may reduce ADHD-like behaviour. Our aim was to investigate potential effects of n-3 PUFA supplementation in an animal model of ADHD. Methods We used spontaneously hypertensive rats (SHR). SHR dams were given n-3 PUFA (EPA and DHA)-enriched feed (n-6/n-3 of 1:2.7) during pregnancy, with their offspring continuing on this diet until sacrificed. The SHR controls and Wistar Kyoto (WKY) control rats were given control-feed (n-6/n-3 of 7:1). During postnatal days (PND) 25–50, offspring were tested for reinforcement-dependent attention, impulsivity and hyperactivity as well as spontaneous locomotion. The animals were then sacrificed at PND 55–60 and their neostriata were analysed for monoamine and amino acid neurotransmitters with high performance liquid chromatography. Results n-3 PUFA supplementation significantly enhanced reinforcement-controlled attention and reduced lever-directed hyperactivity and impulsiveness in SHR males whereas the opposite or no effects were observed in females. Analysis of neostriata from the same animals showed significantly enhanced dopamine and serotonin turnover ratios in the male SHRs, whereas female SHRs showed no change, except for an intermediate increase in serotonin catabolism. In contrast, both male and female SHRs showed n-3 PUFA-induced reduction in non-reinforced spontaneous locomotion, and sex-independent changes in glycine levels and glutamate turnover. Conclusions Feeding n-3 PUFAs to the ADHD model rats induced sex-specific changes in reinforcement-motivated behaviour and a sex-independent change in non-reinforcement-associated behaviour, which correlated with changes in presynaptic striatal monoamine and amino acid signalling, respectively. Thus, dietary n-3 PUFAs may partly ameliorate ADHD-like behaviour by reinforcement-induced mechanisms in males and partly via reinforcement-insensitive mechanisms in both sexes. PMID

  2. Striatal adenosine-cannabinoid receptor interactions in rats over-expressing adenosine A2A receptors.

    PubMed

    Chiodi, Valentina; Ferrante, Antonella; Ferraro, Luca; Potenza, Rosa Luisa; Armida, Monica; Beggiato, Sarah; Pèzzola, Antonella; Bader, Michael; Fuxe, Kjell; Popoli, Patrizia; Domenici, Maria Rosaria

    2016-03-01

    Adenosine A2A receptors (A2 A Rs) and cannabinoid CB1 receptors (CB1 Rs) are highly expressed in the striatum, where they functionally interact and form A2A /CB1 heteroreceptor complexes. We investigated the effects of CB1 R stimulation in a transgenic rat strain over-expressing A2 A Rs under the control of the neural-specific enolase promoter (NSEA2A rats) and in age-matched wild-type (WT) animals. The effects of the CB1 R agonist WIN 55,212-2 (WIN) were significantly lower in NSEA2A rats than in WT animals, as demonstrated by i) electrophysiological recordings of synaptic transmission in corticostriatal slices; ii) the measurement of glutamate outflow from striatal synaptosomes and iii) in vivo experiments on locomotor activity. Moreover, while the effects of WIN were modulated by both A2 A R agonist (CGS 21680) and antagonists (ZM 241385, KW-6002 and SCH-442416) in WT animals, the A2 A R antagonists failed to influence WIN-mediated effects in NSEA2A rats. The present results demonstrate that in rats with genetic neuronal over-expression of A2 A Rs, the effects mediated by CB1 R activation in the striatum are significantly reduced, suggesting a change in the stoichiometry of A2A and CB1 receptors and providing a strategy to dissect the involvement of A2 A R forming or not forming heteromers in the modulation of striatal functions. These findings add additional evidence for the existence of an interaction between striatal A2 A Rs and CB1 Rs, playing a fundamental role in the regulation of striatal functions. We studied A2A -CB1 receptor interaction in transgenic rats over-expressing adenosine A2A receptors under the control of the neuron-specific enolase promoter (NSEA2A ). In these rats, we demonstrated a reduced effect of the CB1 receptor agonist WIN 55,212-2 in the modulation of corticostriatal synaptic transmission and locomotor activity, while CB1 receptor expression level did not change with respect to WT rats. A reduction in the expression of A2A -CB1

  3. Motor System Development Depends on Experience: A Microgravity Study of Rats

    NASA Technical Reports Server (NTRS)

    Walton, Kerry D.; Llinas, Rodolfo R.; Kalb, Robert; Hillman, Dean; DeFelipe, Javier; Garcia-Segura, Luis Miguel

    2003-01-01

    Animals move about their environment by sensing their surroundings and making adjustments according to need. All animals take the force of gravity into account when the brain and spinal cord undertake the planning and execution of movements. To what extent must animals learn to factor in the force of gravity when making neural calculations about movement? Are animals born knowing how to respond to gravity, or must the young nervous system learn to enter gravity into the equation? To study this issue, young rats were reared in two different gravitational environments (the one-G of Earth and the microgravity of low Earth orbit) that necessitated two different types of motor operations (movements) for optimal behavior. We inquired whether those portions of the young nervous system involved in movement, the motor system, can adapt to different gravitational levels and, if so, the cellular basis for this phenomenon. We studied two groups of rats that had been raised for 16 days in microgravity (eight or 14 days old at launch) and compared their walking and righting (ability to go from upside down to upright) and brain structure to those of control rats that developed on Earth. Flight rats were easily distinguished from the age-matched ground control rats in terms of both motor function and central nervous system structure. Mature surface righting predominated in control rats on the day of landing (R+O), while immature righting predominated in the flight rats on landing day and 30 days after landing. Some of these changes appear to be permanent. Several conclusions can be drawn from these studies: (1) Many aspects of motor behavior are preprogrammed into the young nervous system. In addition, several aspects of motor behavior are acquired as a function of the interaction of the developing organism and the rearing environment; (2) Widespread neuroanatomical differences between one-G- and microgravity-reared rats indicate that there is a structural basis for the adaptation

  4. High Blood Pressure Effects on the Blood to Cerebrospinal Fluid Barrier and Cerebrospinal Fluid Protein Composition: A Two-Dimensional Electrophoresis Study in Spontaneously Hypertensive Rats

    PubMed Central

    González-Marrero, Ibrahim; Castañeyra-Ruiz, Leandro; González-Toledo, Juan M.; Castañeyra-Ruiz, Agustín; de Paz-Carmona, Hector; Castro, Rafael; Hernandez-Fernaud, Juan R.; Castañeyra-Perdomo, Agustín; Carmona-Calero, Emilia M.

    2013-01-01

    The aim of the present work is to analyze the cerebrospinal fluid proteomic profile, trying to find possible biomarkers of the effects of hypertension of the blood to CSF barrier disruption in the brain and their participation in the cholesterol and β-amyloid metabolism and inflammatory processes. Cerebrospinal fluid (CSF) is a system linked to the brain and its composition can be altered not only by encephalic disorder, but also by systemic diseases such as arterial hypertension, which produces alterations in the choroid plexus and cerebrospinal fluid protein composition. 2D gel electrophoresis in cerebrospinal fluid extracted from the cistern magna before sacrifice of hypertensive and control rats was performed. The results showed different proteomic profiles between SHR and WKY, that α-1-antitrypsin, apolipoprotein A1, albumin, immunoglobulin G, vitamin D binding protein, haptoglobin and α-1-macroglobulin were found to be up-regulated in SHR, and apolipoprotein E, transthyretin, α-2-HS-glycoprotein, transferrin, α-1β-glycoprotein, kininogen and carbonic anhidrase II were down-regulated in SHR. The conclusion made here is that hypertension in SHR produces important variations in cerebrospinal fluid proteins that could be due to a choroid plexus dysfunction and this fact supports the close connection between hypertension and blood to cerebrospinal fluid barrier disruption. PMID:23401751

  5. Comparison of effects of chronic and acute administration of NG-nitro-L-arginine methyl ester to the rat on inhibition of nitric oxide-mediated responses.

    PubMed Central

    Bryant, C E; Allcock, G H; Warner, T D

    1995-01-01

    1. Vascular responses to acetylcholine and sodium nitroprusside in vivo and in vitro, in the isolated perfused kidney and in rings of rat thoracic aorta, were measured in rats treated chronically with NG-nitro-L-arginine methyl ester (L-NAME; approx, 70 mg kg-1) and compared to responses in age-matched control animals, and age-matched animals after the acute administration of L-NAME (3-100 mumol kg-1). Parallel experiments examined alterations in responsiveness in rings of trachea and anococcygeus muscles taken from the same animals. 2. Chronic oral administration of L-NAME elevated the blood pressure in anaesthetized animals from 114 +/- 5 mmHg to 153 +/- 11 mmHg (n = 5). The hypotensive responses to both acetylcholine (1 nmol kg-1) and sodium nitroprusside (10 nmol kg-1) were enhanced by chronic L-NAME treatment (n = 5-7) whereas acute L-NAME administration enhanced only the response to sodium nitroprusside (n = 5). 3. After chronic treatment with L-NAME, the basal perfusion pressure in the isolated perfused kidney was elevated. However, vasodilator responses to either acetylcholine (1 nmol) or sodium nitroprusside (3 nmol) were unaltered (n = 5-7). The vasodilatation induced by acetylcholine was inhibited in a concentration-dependent manner by the administration of acute L-NAME (0.1 - 100 microM; n = 5), such that significant inhibition was seen at 10 microM L-NAME. The response to sodium nitroprusside was unaffected by L-NAME.(ABSTRACT TRUNCATED AT 250 WORDS) Images Figure 1 Figure 3 PMID:7541283

  6. A computational procedure for identifying master regulator candidates: a case study on diabetes progression in Goto-Kakizaki rats

    PubMed Central

    2012-01-01

    Background We have recently identified a number of active regulatory networks involved in diabetes progression in Goto-Kakizaki (GK) rats by network screening. The networks were quite consistent with the previous knowledge of the regulatory relationships between transcription factors (TFs) and their regulated genes. To study the underlying molecular mechanisms directly related to phenotype changes, such as diseases, we also previously developed a computational procedure for identifying transcriptional master regulators (MRs) in conjunction with network screening and network inference, by effectively perturbing the phenotype states. Results In this work, we further improved our previous method for identifying MR candidates, by listing them in a more reliable manner, and applied the method to reveal the MR candidates for diabetes progression in GK rats from the active networks. Specifically, the active TF-gene pairs for different time periods in GK rats were first extracted from the networks by network screening. Another set of active TF-gene pairs was selected by network inference, by considering the gene expression signatures for those periods between GK and Wistar-Kyoto (WKY) rats. The TF-gene pairs extracted by the two methods were then further selected, from the viewpoints of the emergence specificity of TF in GK rats and the regulated-gene coverage of TF in the expression signature. Finally, we narrowed all of the genes down to only 5 TFs (Etv4, Fus, Nr2f1, Sp2, and Tcfap2b) as the candidates of MRs, with 54 regulated genes, by merging the selected TF-gene pairs. Conclusions The present method has successfully identified biologically plausible MR candidates, including the TFs related to diabetes in previous reports. Although the experimental verifications of the candidates and the present procedure are beyond the scope of this study, we narrowed down the candidates to 5 TFs, which can be used to perform the verification experiments relatively easily. The

  7. The Dynamics of Cortical Neuronal Activity in the First Minutes after Spontaneous Awakening in Rats and Mice

    PubMed Central

    Vyazovskiy, Vladyslav V.; Cui, Nanyi; Rodriguez, Alexander V.; Funk, Chadd; Cirelli, Chiara; Tononi, Giulio

    2014-01-01

    Study Objective: Upon awakening from sleep, a fully awake brain state is not reestablished immediately, but the origin and physiological properties of the distinct brain state during the first min after awakening are unclear. To investigate whether neuronal firing immediately upon arousal is different from the remaining part of the waking episode, we recorded and analyzed the dynamics of cortical neuronal activity in the first 15 min after spontaneous awakenings in freely moving rats and mice. Design: Intracortical recordings of the local field potential and neuronal activity in freely-moving mice and rats. Setting: Basic sleep research laboratory. Patients or Participants: WKY adult male rats, C57BL/6 adult male mice. Interventions: N/A. Measurements and Results: In both species the average population spiking activity upon arousal was initially low, though substantial variability in the dynamics of firing activity was apparent between individual neurons. A distinct population of neurons was found that was virtually silent in the first min upon awakening. The overall lower population spiking initially after awakening was associated with the occurrence of brief periods of generalized neuronal silence (OFF periods), whose frequency peaked immediately after awakening and then progressively declined. OFF periods incidence upon awakening was independent of ongoing locomotor activity but was sensitive to immediate preceding sleep/wake history. Notably, in both rats and mice if sleep before a waking episode was enriched in rapid eye movement sleep, the incidence of OFF periods was initially higher as compared to those waking episodes preceded mainly by nonrapid eye movement sleep. Conclusion: We speculate that an intrusion of sleep-like patterns of cortical neuronal activity into the wake state immediately after awakening may account for some of the changes in the behavior and cognitive function typical of what is referred to as sleep inertia. Citation: Vyazovskiy VV, Cui

  8. Potentiation of mGlu5 receptors with the novel enhancer, VU0360172, reduces spontaneous absence seizures in WAG/Rij rats

    PubMed Central

    D’Amore, V.; Santolini, I.; van Rijn, C.M.; Biagioni, F.; Molinaro, G.; Prete, A.; Conn, P.J.; Lindsley, C.W.; Zhou, Y.; Vinson, P.N.; Rodriguez, A.L.; Jones, C.K.; Stauffer, S.R.; Nicoletti, F.; van Luijtelaar, G.; Ngomba, R.T.

    2013-01-01

    Absence epilepsy is generated by the cortico-thalamo-cortical network, which undergoes a finely tuned regulation by metabotropic glutamate (mGlu) receptors. We have shown previously that potentiation of mGlu1 receptors reduces spontaneous occurring spike and wave discharges (SWDs) in the WAG/Rij rat model of absence epilepsy, whereas activation of mGlu2/3 and mGlu4 receptors produces the opposite effect. Here, we have extended the study to mGlu5 receptors, which are known to be highly expressed within the cortico-thalamo-cortical network. We used presymptomatic and symptomatic WAG/Rij rats and aged-matched ACI rats. WAG/Rij rats showed a reduction in the mGlu5 receptor protein levels and in the mGlu5-receptor mediated stimulation of polyphosphoinositide hydrolysis in the ventrobasal thalamus, whereas the expression of mGlu5 receptors was increased in the somatosensory cortex. Interestingly, these changes preceded the onset of the epileptic phenotype, being already visible in pre-symptomatic WAG/Rij rats. SWDs in symptomatic WAG/Rij rats were not influenced by pharmacological blockade of mGlu5 receptors with MTEP (10 or 30 mg/kg, i.p.), but were significantly decreased by mGlu5 receptor potentiation with the novel enhancer, VU0360172 (3 or 10 mg/kg, s.c.), without affecting motor behaviour. The effect of VU0360172 was prevented by co-treatment with MTEP. These findings suggest that changes in mGlu5 receptors might lie at the core of the absence-seizure prone phenotype of WAG/Rij rats, and that mGlu5 receptor enhancers are potential candidates to the treatment of absence epilepsy. PMID:22705340

  9. Potentiation of mGlu5 receptors with the novel enhancer, VU0360172, reduces spontaneous absence seizures in WAG/Rij rats.

    PubMed

    D'Amore, V; Santolini, I; van Rijn, C M; Biagioni, F; Molinaro, G; Prete, A; Conn, P J; Lindsley, C W; Zhou, Y; Vinson, P N; Rodriguez, A L; Jones, C K; Stauffer, S R; Nicoletti, F; van Luijtelaar, G; Ngomba, R T

    2013-03-01

    Absence epilepsy is generated by the cortico-thalamo-cortical network, which undergoes a finely tuned regulation by metabotropic glutamate (mGlu) receptors. We have shown previously that potentiation of mGlu1 receptors reduces spontaneous occurring spike and wave discharges (SWDs) in the WAG/Rij rat model of absence epilepsy, whereas activation of mGlu2/3 and mGlu4 receptors produces the opposite effect. Here, we have extended the study to mGlu5 receptors, which are known to be highly expressed within the cortico-thalamo-cortical network. We used presymptomatic and symptomatic WAG/Rij rats and aged-matched ACI rats. WAG/Rij rats showed a reduction in the mGlu5 receptor protein levels and in the mGlu5-receptor mediated stimulation of polyphosphoinositide hydrolysis in the ventrobasal thalamus, whereas the expression of mGlu5 receptors was increased in the somatosensory cortex. Interestingly, these changes preceded the onset of the epileptic phenotype, being already visible in pre-symptomatic WAG/Rij rats. SWDs in symptomatic WAG/Rij rats were not influenced by pharmacological blockade of mGlu5 receptors with MTEP (10 or 30 mg/kg, i.p.), but were significantly decreased by mGlu5 receptor potentiation with the novel enhancer, VU0360172 (3 or 10 mg/kg, s.c.), without affecting motor behaviour. The effect of VU0360172 was prevented by co-treatment with MTEP. These findings suggest that changes in mGlu5 receptors might lie at the core of the absence-seizure prone phenotype of WAG/Rij rats, and that mGlu5 receptor enhancers are potential candidates to the treatment of absence epilepsy. This article is part of a Special Issue entitled 'Metabotropic Glutamate Receptors'. PMID:22705340

  10. Effect of L-NAME-induced hypertension on melatonin receptors and melatonin levels in the pineal gland and the peripheral organs of rats.

    PubMed

    Benova, Miroslava; Herichova, Iveta; Stebelova, Katarina; Paulis, Ludovit; Krajcirovicova, Kristina; Simko, Fedor; Zeman, Michal

    2009-04-01

    Melatonin plays a role in blood pressure (BP) control. The aim of this study was to determine whether melatonin concentrations and melatonin receptor levels are altered in L-NAME-treated, NO-deficient hypertensive rats. Two groups of male adult Wistar rats were investigated: rats (n=36) treated with NO-synthase inhibitor L-NAME (40 mg kg(-1)) and age-matched controls (n=36). BP was measured weekly by tail-cuff plethysmography. After 4 weeks, L-NAME administration increased BP (178+/-1 vs. control 118+/-1 mm Hg). At the end of treatment, rats were killed in regular 4 h intervals over a 24-h period. Melatonin concentrations in the plasma, pineal gland, heart and kidney and melatonin receptor (MT(1)) density in the aorta were determined. A significant daily rhythm of melatonin concentrations was found in the blood, pineal gland, kidney and heart of both control and hypertensive rats. Peak nighttime pineal melatonin concentrations were higher in L-NAME-treated rats than in controls (3.38+/-0.48 vs. 1.75+/-0.33 ng per pineal gland). No differences between both groups were found in melatonin concentrations in blood, kidney and heart or in the MT(1) receptor density in the aorta. Our results suggest that L-NAME treatment enhances melatonin production in the pineal gland, potentially by decreasing an inhibitory effect of NO on melatonin production in the pineal gland. However, the enhanced pineal melatonin formation was insufficient to increase melatonin concentrations in circulation, heart and kidney of L-NAME-treated rats, indicating an increased use of melatonin in hypertensive animals. PMID:19262491

  11. Fibulin-3 may improve vascular health through inhibition of MMP-2/9 and oxidative stress in spontaneously hypertensive rats

    PubMed Central

    LIN, ZHONGWEI; WANG, ZHUO; LI, GUOBIAO; LI, BOWEI; XIE, WENLIN; XIANG, DINGCHENG

    2016-01-01

    Fibulin-3 has been suggested to function in the remodeling of the extracellular matrix, however its role remains unclear in hypertensive vascular remodeling. In the current study, 10 Wistar-Kyoto (WKY) rats (control group) and 30 spontaneously hypertensive rats (SHRs) were used. SHRs were randomized into three groups: The placebo group, intravenous (I.V.) physiological saline; the FBLN-1 group, low-dose fibulin-3 protein (I.V.; 120 ng/kg); and the FBLN-2 group, high-dose fibulin-3 protein (I.V.; 240 ng/kg). Histological analysis was used to analyze vascular remodeling. The expression of fibulin-3, matrix metalloproteinase (MMP)-2, MMP-9 and tissue inhibitor of metalloproteinase (TIMP)-3 were detected by immunohistochemistry, western blotting and reverse transcription-quantitative polymerase chain reaction. Oxidative stress was detected by dihydroethidium staining. The systolic blood pressure (SBP) of SHRs was observed to be significantly greater than that of WKY rats (P<0.05). SBP in the FBLN-2 group was significantly reduced compared with the placebo group (182±12 mmHg vs. 224±14 mmHg; P<0.05). The thoracic aortic wall thickness in the SHR groups (placebo group, FBLN-1 group and FBLN-2 group) was observed to tbe significantly thicker than in the control group (P<0.01). The wall thickness of the FBLN-2 group was significantly greater than that of the placebo and FBLN-1 groups (124.2±11.8 μm vs. 106.9±9.5 μm and 96.8±10.2 μm; P<0.05). The wall-to-lumen ratios of the placebo, FBLN-1 and FBLN-2 groups were significantly greater than that of the control group (P<0.05). In addition, the expression levels of fibulin-3 and MMP-2/9 at protein and mRNA levels were significantly increased in the thoracic aorta of the placebo group compared with the control group (P<0.05). The levels of MMP-2/9 were significantly reduced in the FBLN-2 group compared with the placebo group (P<0.05). Levels of TIMP-3 however, exhibited no significant differences in the four groups (P>0

  12. Attenuation of nitric oxide- and prostaglandin-independent vasodilation of retinal arterioles induced by acetylcholine in streptozotocin-treated rats.

    PubMed

    Nakazawa, Taisuke; Kaneko, Yoshiko; Mori, Asami; Saito, Maki; Sakamoto, Kenji; Nakahara, Tsutomu; Ishii, Kunio

    2007-03-01

    Diabetes alters retinal hemodynamics, but little is known about the impact of diabetes on the role of endothelium-derived hyperpolarizing factor (EDHF) in the regulation of retinal circulation. Therefore, we examined how diabetes affects the nitric oxide- and prostaglandin-independent vasodilation of retinal arterioles induced by acetylcholine. Male Wistar rats were treated with streptozotocin (80 mg/kg, i.p.) and experiments were performed 6-8 weeks later. Under artificial ventilation, rats were treated with tetrodotoxin (100 microg/kg, i.v.) to eliminate any nerve activity and prevent movement of the eye. Methoxamine was used to maintain adequate systemic circulation. Fundus images were captured by a digital camera that was equipped with a special objective lens. The vasodilator responses of retinal arterioles were assessed by measuring changes in diameters of the vessels. In streptozotocin-induced diabetic rats and the age-matched controls, acetylcholine increased diameters of retinal arterioles in a dose-dependent manner. The vasodilator responses to acetylcholine in diabetic rats were smaller than those in control rats. The nitric oxide- and prostaglandin-independent vasodilation of retinal arterioles observed under treatment with combination of N(G)-nitro-l-arginine methyl ester (30 mg/kg, i.v.) and indomethacin (5 mg/kg, i.v.) were also attenuated by diabetes. Diabetes did not alter the dilator responses of retinal arterioles to sodium nitroprusside and forskolin. These results suggest that diabetes impairs EDHF-mediated vasodilation of retinal arterioles induced by acetylcholine. The impaired EDHF-mediated vasodilation may contribute to alteration of retinal hemodynamics in diabetes. PMID:17079193

  13. Measurement of Retinal Blood Flow Rate in Diabetic Rats: Disparity Between Techniques Due to Redistribution of Flow

    PubMed Central

    Leskova, Wendy; Watts, Megan N.; Carter, Patsy R.; Eshaq, Randa S.; Harris, Norman R.

    2013-01-01

    Purpose. Reports of altered retinal blood flow in experimental models of type I diabetes have provided contrasting results, which leads to some confusion as to whether flow is increased or decreased. The purpose of our study was to evaluate early diabetes-induced changes in retinal blood flow in diabetic rats, using two distinctly different methods. Methods. Diabetes was induced by injection of streptozotocin (STZ), and retinal blood flow rate was measured under anesthesia by a microsphere infusion technique, or by an index of flow based on the mean circulation time between arterioles and venules. Measurements in STZ rats were compared to age-matched nondiabetic controls. In addition, the retinal distribution of fluorescently-labeled red blood cells (RBCs) was viewed by confocal microscopy in excised flat mounts. Results. Retinal blood flow rate was found to decrease by approximately 33% in the STZ rats compared to controls (P < 0.001) as assessed by the microsphere technique. However, in striking contrast, the mean circulation time through the retina was found to be almost 3× faster in the STZ rats (P < 0.01). This contradiction could be explained by flow redistribution through the superficial vessels of the diabetic retina, with this possibility supported by our observation of significantly fewer RBCs flowing through the deeper capillaries. Conclusions. We conclude that retinal blood flow rate is reduced significantly in the diabetic rat, with a substantial decrease of flow through the capillaries due to shunting of blood through the superficial layer, allowing rapid transit from arterioles to venules. PMID:23572104

  14. Anti-hypertensive property of a nickel-piperazine/NO donor in spontaneously hypertensive rats.

    PubMed

    Monti, Martina; Ciccone, Valerio; Pacini, Aurora; Roggeri, Riccardo; Monzani, Enrico; Casella, Luigi; Morbidelli, Lucia

    2016-05-01

    The nickel-piperazine/NO donor compound, Ni(PipNONO)Cl, belonging to the family of compounds labelled as "metal-nonoates", due to its promising vasodilating activity, has been considered as a potential drug candidate in anti-hypertensive therapy. Drug efficacy has been evaluated in spontaneously hypertensive rats (SHR) in comparison with normotensive animals (C57BL/6 mice and WKY rats). In normotensive animals the metal-nonoate maintained blood pressure at basal level both following acute administration and after 30 days of treatment. In SHR, Ni(PipNONO)Cl reduced blood pressure in the dose range of 3-10mg/kg. When compared with a commercial NONOate, DETA/NO, used at the same doses, Ni(PipNONO)Cl was more active in reducing blood pressure in SHR than DETA/NO in the first two weeks, while the effect of the two molecules was similar in the third and fourth week. The degradation and control compound Ni(Pip)Cl2 had no effect on blood pressure and heart rate in same animal models. Remarkably, the blood pressure reduction induced by the new NO-donor Ni(PipNONO)Cl does not evoke changes in the heart rate and tolerance. Considering the mechanisms of vascular protection, 30 days of administration of Ni(PipNONO)Cl improved endothelial function in SHR by upregulating endothelial NO synthase (eNOS) through increased eNOS protein levels and downregulated Caveolin-1 (Cav-1), and by increasing superoxide dismutase 1 (SOD1) protein level in aortae. In cultured endothelial cells Ni(PipNONO)Cl restored the cell functions (cytoskeletal protein expression, migration and proliferation) altered by the inflammatory mediator interleukin-1β (IL-1β), impairing the endothelial to mesenchimal transition. In conclusion, Ni(PipNONO)Cl maintained unaltered blood pressure in normotensive mice and rats, and it exerted anti-hypertensive effect in SHR through the restoration of vascular endothelial protective functions. PMID:27063892

  15. Roles of Zinc and Iron on Bone Health in a Rat Model of Osteoporosis

    NASA Astrophysics Data System (ADS)

    Yan, Danhua

    Bone is one of the most vital organs in animals, serving as both structural and protective functions. Remodeling of bone is an important indicator of bone health, and disorders in bone remodeling may lead to bone diseases such as osteoporosis. Osteoporosis increases risk of bone fracture and even death, and much more preferable to be happened in postmenopausal women due to great changes in hormones. Micronutrients, such as Zinc (Zn) and Iron (Fe), would as well influence bone health in different manners. That Zn would promote bone health is widely accepted, for the reasons Zn increases osteoblast cell proliferation and differentiation, inhibits osteoclast cell activities, and forms alkaline phosphatase that does help to maintain bone metabolism. Diseases caused by Fe overload is usually related to osteoporosis. Ferric ion could facilitate osteoclast differentiation, inhibit osteoblast and alkaline phosphatase activities, and interfere with hydroxyapatite crystal growth and depositions. However, changes of concentrations and distributions for Zn and Fe in osteoporotic bones are seldom studied. In this thesis, ovariectomized rat femur bones are used as a model of postmenopausal osteoporosis. Rats from different ages and health conditions are categorized as 6 AM (6-month age matched control), 6 OVX (6-month ovariectomized control), 12 AM (12-month age matched control), 12 OVX (12-month ovariectomized control). The trace elements Zn and Fe is studied through Synchrotron Radiation X-Ray Fluorescence (SRXRF). Elemental maps are used to observe changes in distribution, and further quantitative analysis is used to discover changes in concentration among different animal groups. Both the decrease of Zn and the increase of Fe are significant from healthy to osteoporotic bones (p<0.05). In the meanwhile, accumulation of Zn (p<0.05) and Fe (p>0.1) is also observed over age in healthy groups. Both elements show changes in distribution, that healthy animals present a more even

  16. Restoring and maintaining bone in osteopenic female rat skeleton: I. Changes in bone mass and structure

    NASA Technical Reports Server (NTRS)

    Tang, L. Y.; Jee, W. S.; Ke, H. Z.; Kimmel, D. B.

    1992-01-01

    This experiment contains the crucial data for the lose, restore, and maintain (LRM) concept, a practical approach for reversing existing osteoporosis. The LRM concept uses anabolic agents to restore bone mass and architecture (+ phase) and then switches to an agent with the established ability to maintain bone mass, to keep the new bone (+/- phase). The purpose of this study was to learn whether switching to an agent known chiefly for its ability to maintain existing bone mass preserves new bone induced by PGE2 in osteopenic, estrogen-depleted rats. The current study had three phases, the bone loss (-), restore (+), and maintain (+/-) phases. We ovariectomized (OX) or sham ovariectomized (sham-OX) 5.5-month-old female rats (- phase). The OX rats were treated 5 months postovariectomy with 1-6 mg PGE2 per kg/day for 75 days to restore lost cancellous bone mass (+ phase), and then PGE2 treatment was stopped and treatment began with 1 or 5 micrograms/kg of risedronate, a bisphosphonate, twice a week for 60 days (+/- phase). During the loss (-) phase, the cancellous bone volume of the proximal tibial metaphysis in the OX rat fell to 19% of initial and 30% of age-matched control levels. During the restore (+) phase, the cancellous bone volume in OX rats doubled. When PGE2 treatment was stopped, however, and no special maintenance efforts were made during the maintain (+/-) phase, the PGE2-induced cancellous bone disappeared. In contrast, the PGE2-induced cancellous bone persisted when the PGE2 treatment was followed by either a 1 or 5 micrograms treatment of risedronate per kg given twice a week for 60 days during the maintain (+/-) phase. The tibial shaft demonstrated very little cortical bone loss during the loss (-) phase in OX rats. The tibial shaft cortical bone fell some 8%. During the restore (+) phase, new cortical bone in OX rats increased by 22%. When PGE2 treatment was stopped and nothing was given during the maintain (+/-) phase, however, all but the PGE2

  17. Acute intermittent hypoxia induced phrenic long-term facilitation despite increased SOD1 expression in a rat model of ALS.

    PubMed

    Nichols, Nicole L; Satriotomo, Irawan; Harrigan, Daniel J; Mitchell, Gordon S

    2015-11-01

    Amyotrophic lateral sclerosis (ALS) is a progressive and fatal neurodegenerative disease characterized by motor neuron death. Since most ALS patients succumb to ventilatory failure from loss of respiratory motor neurons, any effective ALS treatment must preserve and/or restore breathing capacity. In rats over-expressing mutated super-oxide dismutase-1 (SOD1(G93A)), the capacity to increase phrenic motor output is decreased at disease end-stage, suggesting imminent ventilatory failure. Acute intermittent hypoxia (AIH) induces phrenic long-term facilitation (pLTF), a form of spinal respiratory motor plasticity with potential to restore phrenic motor output in clinical disorders that compromise breathing. Since pLTF requires NADPH oxidase activity and reactive oxygen species (ROS) formation, it is blocked by NADPH oxidase inhibition and SOD mimetics in normal rats. Thus, we hypothesized that SOD1(G93A) (mutant; MT) rats do not express AIH-induced pLTF due to over-expression of active mutant superoxide dismutase-1. AIH-induced pLTF and hypoglossal (XII) LTF were assessed in young, pre-symptomatic and end-stage anesthetized MT rats and age-matched wild-type littermates. Contrary to predictions, pLTF and XII LTF were observed in MT rats at all ages; at end-stage, pLTF was actually enhanced. SOD1 levels were elevated in young and pre-symptomatic MT rats, yet superoxide accumulation in putative phrenic motor neurons (assessed with dihydroethidium) was unchanged; however, superoxide accumulation significantly decreased at end-stage. Thus, compensatory mechanisms appear to maintain ROS homoeostasis until late in disease progression, preserving AIH-induced respiratory plasticity. Following intrathecal injections of an NADPH oxidase inhibitor (apocynin; 600 μM; 12 μL), pLTF was abolished in pre-symptomatic, but not end-stage MT rats, demonstrating that pLTF is NADPH oxidase dependent in pre-symptomatic, but NADPH oxidase independent in end-stage MT rats. Mechanisms

  18. Effect of vitamin K2 on cortical and cancellous bone mass and hepatic lipids in rats with combined methionine-choline deficiency.

    PubMed

    Iwamoto, Jun; Seki, Azusa; Sato, Yoshihiro; Matsumoto, Hideo; Takeda, Tsuyoshi; Yeh, James K

    2011-05-01

    The present study examined changes of cancellous and cortical bone in rats with combined methionine-choline deficiency (MCD). In addition, the effects of vitamin K2 on cortical and cancellous bone mass and hepatic lipids were investigated in rats with MCD. Six-week-old male Sprague-Dawley rats were randomized into three groups of ten, including an age-matched control (standard diet) group, an MCD diet group, and an MCD diet+vitamin K2 (menatetrenone at 30mg/kg/d orally, 5 times a week) group. After the one-month experimental period, histomorphometric analysis was performed on cortical and cancellous bone from the tibial diaphysis and proximal metaphysis, respectively, while histological examination of the liver was performed after staining with hematoxylin and eosin and Oil Red O. MCD rats displayed weight loss, diffuse and centrilobular fatty changes of the liver, and a decrease of the cancellous bone volume per tissue volume (BV/TV) and percent cortical area (Ct Ar) as a result of decreased trabecular, periosteal, and endocortical bone formation along with increased trabecular and endocortical bone resorption. Administration of vitamin K2 to rats with MCD attenuated weight loss, accelerated the decrease of cancellous BV/TV due to an increase of bone remodeling, and ameliorated the decrease of percent Ct Ar by increasing periosteal and endocortical bone formation. Vitamin K2 administration also prevented MCD-induced diffuse fatty change of the liver. These findings suggest a beneficial effect of vitamin K2 on cortical bone mass and hepatic lipid metabolism in rats with MCD. The loss of cancellous bone mass could possibly have been due to re-distribution of minerals to cortical bone. PMID:21352961

  19. Biosynthesis of collagen crosslinks. III. In vivo labeling and stability of lung collagen in rats with bleomycin-induced pulmonary fibrosis

    SciTech Connect

    Last, J.A.; Reiser, K.M. )

    1989-08-01

    Rats were injected intraperitoneally with 1 mCi (each) of (3H)lysine at Day 11 of neonatal life to label their lung collagen. Five weeks later, half of the animals were given an intratracheal injection of 1.5 U of bleomycin sulfate via a tracheostomy; control animals received saline intratracheally by the same technique. Age-matched groups of control and bleomycin-treated rats were killed, and their lung collagen was analyzed at zero (control animals only), 1, 2, 4, 6, and 10 wk after bleomycin administration, a time course appropriate for development of pulmonary fibrosis in this animal model. We measured radioactivity in hydroxylysine and in the difunctional collagen crosslinks hydroxylysinonorleucine and dihydroxylysinonorleucine at each time point. No evidence of breakdown of this pool of mature, preformed collagen was observed in lungs of either the control or the bleomycin-treated rats. We also measured the total lung content of hydroxypyridinium, a trifunctional collagen crosslink, by its intrinsic fluorescence. There was no evidence of collagen degradation in lungs of either group of rats by this criterion either. We conclude that there is no biochemically detectable turnover of mature lung collagen, defined as that pool of lung collagen that is obligatorily extracellular (i.e., crosslinked and containing labeled hydroxylysine from an injection of precursor 5 to 15 wk earlier), in either normal rat lungs or lungs of rats made fibrotic with bleomycin. Statistical analysis of the data suggests that our methodology was sensitive and precise enough to have detected turnover of less than 0.5% of lung collagen per day, some 20-fold less than estimates of lung collagen turnover that have been suggested to be occurring in vivo by others using different techniques and presumably studying different pools of lung collagen.

  20. Protective effects of tocotrienols against lipid-induced nephropathy in experimental type-2 diabetic rats by modulation in TGF-β expression.

    PubMed

    Siddiqui, Shabeena; Ahsan, Haseeb; Khan, Mohammad Rashid; Siddiqui, Waseem A

    2013-12-01

    Dyslipidemia is common in patients with diabetes mellitus (DM) and is considered a risk factor for the progression of diabetic nephropathy (DN). Hyperlipidemia and hyperglycemia act synergistically to induce renal injury. The present study was designed to investigate the protective effects of tocotrienols as tocotrienol-rich fraction (TRF) extracted from palm (PO) and rice bran oils (RBO) against lipid induced nephropathy in type-2 diabetic rats and its probable molecular mechanism. Male Wistar rats (175-200 g) were divided into four groups. The first group served as diabetic control, while the second and third groups received PO-TRF and RBO-TRF, respectively by gavage over a period of sixteen weeks post-induction of diabetes. The fourth group comprised of age-matched rats that served as normal control. The effects of TRF on serum lipid profile, oxidative stress markers, expression of TGF-β, fibronectin and collagen type IV were analyzed in the kidney of diabetic rats. Treatment with PO-TRF and RBO-TRF significantly improved glycemic status, serum lipid profile and renal function in type-2 diabetic rats. In addition, TRF supplementation down-regulated the expression of TGF-β, fibronectin and collagen type IV in the kidney of diabetic rats. Transforming growth factor-β (TGF-β) plays a critical role in progression of DN, but its modulation by tocotrienols in DN remains unexplored. TRF ameliorated lipid induced nephropathy in type-2 diabetes by its hypoglycemic, hypolipidemic and antioxidant activities as well as by modulation of TGF-β to prevent increased expression of collagen type IV and fibrinogen. We finally propose a mechanism for the expression of molecular markers that are significant in the events leading to diabetic nephropathy and its modulation by tocotrienols/TRF. PMID:24041758

  1. Androgen-mediated development of irradiation-induced thyroid tumors in rats: dependence on animal age during interval of androgen replacement in castrated males

    SciTech Connect

    Hofmann, C.; Oslapas, R.; Nayyar, R.; Paloyan, E.

    1986-07-01

    When male Long-Evans rats at age 8 weeks were radiation treated (40 microCi Na131I), thyroid follicular adenomas and carcinomas were observed at age 24 months with a high incidence of 94%. Castration of males prior to irradiation significantly reduced this tumor incidence to 60%. When testosterone (T) was replaced in castrated, irradiated male rats, differentially increased