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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. Strain Differences in the Expression of Dopamine D1 Receptors in Wistar-Kyoto (WKY) and Wistar Rats

    PubMed Central

    Novick, Andrew; Yaroslavsky, Irene; Tejani-Butt, Shanaz

    2008-01-01

    The Wistar-Kyoto (WKY) rat is a stress-sensitive strain that is prone to depressive-like behavior in various experimental paradigms. While recent work has highlighted a role for dopamine (DA) in the pathology of depression, research on the WKY rat has also suggested that dysfunction of DA pathways may be an important component of the behavior in this strain. Previous work has demonstrated differential patterns of dopamine transporter sites, dopamine D2 and D3 receptors in the WKY rats compared to control strains. To further this work, the present study utilized autoradiographic analysis of [3H]-SCH23390 binding to DA D1 receptors in various brain regions of naïve male WKY and Wistar (WIS) rats. The results revealed a significant strain difference, with WKY rats demonstrating lower D1 binding in the caudate putamen and regions of the nucleus accumbens (p<0.05). An opposite pattern was found in the substantia nigra pars reticulata where D1 binding was higher in WKY rats compared to WIS rats (p<0.05). Because the D1 receptor represents a critical site where DA acts to modify behavior related to depression, the altered expression of this receptor in the WKY rat found in the present study may be reflective of the depressive susceptibility noted in this strain. PMID:18558411

  4. Acute and chronic psychostimulant treatment modulates the diurnal rhythm activity pattern of WKY female adolescent rats.

    PubMed

    Jones, Cathleen G; Yang, Pamela B; Wilcox, Victor T; Burau, Keith D; Dafny, Nachum

    2014-05-01

    The psychostimulants considered the gold standard in the treatment of attention deficit hyperactivity disorder, one of the most common childhood disorders, are also finding their way into the hands of healthy young adults as brain augmentation to improve cognitive performance. The possible long-term effects of psychostimulant exposure in adolescence are considered controversial, and thus, the objective of this study was to investigate whether the chronic exposure to the psychostimulant amphetamine affects the behavioral diurnal rhythm activity patterns of female adolescent Wistar-Kyoto (WKY) rat. The hypothesis of this study is that change in diurnal rhythm activity pattern is an indicator for the long-term effect of the treatment. Twenty-four rats were divided into two groups, control (N = 12) and experimental (N = 12), and kept in a 12:12-h light/dark cycle in an open-field cage. After 5-7 days of acclimation, 11 days of consecutive non-stop behavioral recordings began. On experimental day 1 (ED1), all groups were given an injection of saline. On ED2 to ED7, the experimental group was injected with 0.6 mg/kg amphetamine followed by 3 days of washout from ED8 to ED10, and amphetamine re-challenge on ED11 similar to ED2. The locomotor movements were counted by the computerized animal activity monitoring system, and the cosinor statistical test analysis was used to fit a 24-h curve of the control recording to the activity pattern after treatment. The horizontal activity, total distance, number of stereotypy, vertical activity, and stereotypical movements were analyzed to find out whether the diurnal rhythm activity patterns were altered. Data obtained using these locomotor indices of diurnal rhythm activity pattern suggest that amphetamine treatment significantly modulates the locomotor diurnal rhythm activity pattern of female WKY adolescent rats.

  5. Oxytocin differently regulates pressor responses to stress in WKY and SHR rats: the role of central oxytocin and V1a receptors.

    PubMed

    Wsol, A; Szczepanska-Sadowska, E; Kowalewski, S; Puchalska, L; Cudnoch-Jedrzejewska, A

    2014-01-01

    The role of central oxytocin in the regulation of cardiovascular parameters under resting conditions and during acute stress was investigated in male normotensive Wistar-Kyoto (WKY; n = 40) and spontaneously hypertensive rats (SHR; n = 28). In Experiment 1, mean arterial blood pressure (MABP) and heart rate (HR) were recorded in WKY and SHR rats at rest and after an air-jet stressor during intracerebroventricular (ICV) infusions of vehicle, oxytocin or oxytocin receptor (OTR) antagonist. In Experiment 2, the effects of vehicle, oxytocin and OTR antagonist were determined in WKY rats after prior administration of a V1a vasopressin receptor (V1aR) antagonist. Resting MABP and HR were not affected by any of the ICV infusions either in WKY or in SHR rats. In control experiments (vehicle), the pressor response to stress was significantly higher in SHR. Oxytocin enhanced the pressor response to stress in the WKY rats but reduced it in SHR. During V1aR blockade, oxytocin infusion entirely abolished the pressor response to stress in WKY rats. Combined blockade of V1aR and OTR elicited a significantly greater MABP response to stress than infusion of V1a antagonist and vehicle. This study reveals significant differences in the regulation of blood pressure in WKY and SHR rats during alarming stress. Specifically, the augmentation of the pressor response to stress by exogenous oxytocin in WKY rats is caused by its interaction with V1aR, and endogenous oxytocin regulates the magnitude of the pressor response to stress in WKY rats by simultaneous interaction with OTR and V1aR.

  6. Prematurely delivered rats show improved motor coordination during sensory-evoked motor responses compared to age-matched controls.

    PubMed

    Roberto, Megan E; Brumley, Michele R

    2014-05-10

    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.

  7. Ozone Induced Impairment of Systemic Metabolic Processes: Influence of Prior Ozone Exposure and Metformin Pre-treatment on Aged Wistar Kyoto (WKY) Rats.

    EPA Science Inventory

    SOT2014 Abstract for presentation: March 23-27, 2014; Phoenix, AZ Ozone Induced Impairment of Systemic Metabolic Processes: Influence of Prior Ozone Exposure and Metformin Pre-treatment on Aged Wistar Kyoto (WKY) Rats. V. Bass, D. Andrews, J. Richards, M. Schladweiler, A. Ledb...

  8. Electrophysiological properties and augmented catecholamine release from chromaffin cells of WKY and SHR rats contributing to the hypertension development elicited by chronic EtOH consumption.

    PubMed

    Bomfim, Guilherme Henrique Souza; Méndez-López, Iago; Fernández-Morales, José Carlos; Padín, Juan Fernando; Jurkiewicz, Aron; Jurkiewicz, Neide Hyppolito; García, Antonio García

    2017-03-16

    It is known that chronic ethanol (EtOH) consumption leads to hypertension development and has been associated with deleterious effects on the cardiovascular system. Whether this condition alters calcium (Ca(2+)) signaling and exocytosis in adrenal chromaffin cells (CCs) as the case is for genetic hypertension, is unknown. We explored this question in four randomized experimental groups, male Wistar Kyoto (WKY/EtOH) and Spontaneously Hypertensive (SHR/EtOH) rats were subjected to the intake of increasing EtOH concentrations (5-20%, for 30 days) and their respective controls (WKY/Control and SHR/Control) received water. WKY/EtOH developed hypertension and cardiac hypertrophy; blood aldehyde dehydrogenase (ALDH) and H2O2 were also augmented. In comparison with WKY/Control, CCs from WKY/EtOH had the following features: (i) depolarization and higher frequency of spontaneous action potentials; (ii) decreased Ca(2+) currents with slower inactivation; (iii) decreased K(+) currents; (iv) augmented K(+)-elicited cytosolic Ca(2+) transients ([Ca(2+)]c); (v) enhanced K(+)-elicited catecholamine release. These cardiovascular, blood and CCs changes were qualitatively similar to those undergone by SHR/Control and SHR/EtOH. The results suggest that the hypertension elicited by chronic EtOH has pathogenic features common to genetic hypertension namely, augmented [Ca(2+)]c transients and catecholamine release from their CCs.

  9. 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...

  10. 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

  11. 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.

  12. 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

  13. 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...

  14. 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.

  15. Differential gene expression in liver and small intestine from lactating rats compared to age-matched virgin controls detects increased mRNA of cholesterol biosynthetic genes

    PubMed Central

    2011-01-01

    Background Lactation increases energy demands four- to five-fold, leading to a two- to three-fold increase in food consumption, requiring a proportional adjustment in the ability of the lactating dam to absorb nutrients and to synthesize critical biomolecules, such as cholesterol, to meet the dietary needs of both the offspring and the dam. The size and hydrophobicity of the bile acid pool increases during lactation, implying an increased absorption and disposition of lipids, sterols, nutrients, and xenobiotics. In order to investigate changes at the transcriptomics level, we utilized an exon array and calculated expression levels to investigate changes in gene expression in the liver, duodenum, jejunum, and ileum of lactating dams when compared against age-matched virgin controls. Results A two-way mixed models ANOVA was applied to detect differentially expressed genes. Significance calls were defined as a p < 0.05 for the overall physiologic state effect (lactation vs. control), and a within tissue pairwise comparison of p < 0.01. The proportion of false positives, an estimate of the ratio of false positives in the list of differentially expressed genes, was calculated for each tissue. The number of differentially expressed genes was 420 in the liver, 337 in the duodenum, 402 in the jejunum, and 523 in the ileum. The list of differentially expressed genes was in turn analyzed by Ingenuity Pathways Analysis (IPA) to detect biological pathways that were overrepresented. In all tissues, sterol regulatory element binding protein (Srebp)-regulated genes involved in cholesterol synthesis showed increased mRNA expression, with the fewest changes detected in the jejunum. We detected increased Scap mRNA in the liver only, suggesting an explanation for the difference in response to lactation between the liver and small intestine. Expression of Cyp7a1, which catalyzes the rate limiting step in the bile acid biosynthetic pathway, was also significantly increased in liver. In

  16. Decreased angiotensin II binding affinity and binding capacity in the anterior pituitary gland of adult spontaneously hypertensive rats

    SciTech Connect

    Gutkind, J.S.; Castren, E.; Saavedra, J.M.

    1988-01-01

    Angiotensin II (ANG) binding sites were quantified in single pituitary glands from 4-week-old and 14-week-old male spontaneously hypertensive rats (SHR) and age-matched male normotensive Wistar-Kyoto (WKY) control rats after incubation with /sup 125/I-(Sar/sup 1/)-ANG, autoradiography with computerized densitometry, and comparison to /sup 125/I-standards. The maximum binding capacity (B/sub max/) decreased while the dissociation constant (K/sub d/) for ANG increased in 14-week-old SHR when compared to age-matched WKY control rats. Conversely, no difference between rat strains was found in 4-week-old animals. Our results suggest that pituitary ANG binding sites may play a role in the pathophysiology of established genetic hypertension.

  17. 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.

  18. 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.

  19. Platelet serotonin content and uptake in spontaneously hypertensive rats

    SciTech Connect

    Guicheney, P.; Legros, M.; Marcel, D.; Kamal, L.; Meyer, P.

    1985-02-18

    Platelet serotonin (5-HT) content and uptake were studied in male SHR and WKY at various ages. Blood was withdrawn from the carotid artery under anesthesia and 5-HT levels determined from platelet rich plasma (PRP) using a HPLC technique coupled with an electrochemical detection method. Platelet 5-HT uptake was studied by incubating PRP at 37/sup 0/C for 10 sec with increasing concentrations of /sup 3/H-5HT. Lineweaver-Burk plots of /sup 3/H-5HT uptake were linear suggesting simple Michaelis-Menten uptake kinetics. The SHR had more platelets than age-matched controls and consequently a higher blood circulating pool of 5-HT. Nevertheless, the 5-HT platelet levels were similar to those of their age-matched rats. The 5 week-old SHR and WKY had greater numbers of platelets and higher 5-HT platelet levels than the older rats of both strains. The affinity constants (Km) and the maximal velocities (Vmax) of platelet 5-HT uptake did not differ significantly between the 12 week- and the 6 month-old SHR and WKY. These data suggest that the SHR do not show the same impairment in platelet 5-HT metabolism as observed in essential hypertension in man.

  20. Beta-adrenoceptors in kidney tubules of spontaneously hypertensive and normotensive rats

    SciTech Connect

    Struyker-Boudier, H.A.J.; Vervoort-Peters, L.H.T.M.; Rousch, M.J.M.; Smits, J.F.M.; Thijssen, H.H.W.

    1986-01-13

    Beta-adrenoceptor binding characteristics were determined in different fractions of rat kidney tubules using a (/sup 125/Iodo)-(-)-cyanopindolol (ICYP) binding assay. The highest amount of binding sites was found in a fraction containing predominantly distal tubular fragments. In a separate series of experiments the ICYP binding characteristics were compared in whole tubular fractions from spontaneously hypertensive (SHR) and normotensive Wistar Kyoto rats (WKY) of different ages. The maximum number of binding sites was significantly higher both in young (3 weeks) and adult (14 weeks) SHR when compared to age-matched WKY. These studies showed the presence of beta-adrenoceptor binding sites in rat kidney tubules and support the potential importance of tubular beta-adrenoceptors in the development of spontaneous hypertension and in the mechanism of antihypertensive action of beta-blockers. 35 references, 1 figure, 3 tables.

  1. Alterations in substance P binding in brain nuclei of spontaneously hypertensive rats

    SciTech Connect

    Shigematsu, K.; Niwa, M.; Kurihara, M.; Castren, E.; Saavedra, J.M.

    1987-02-01

    Substance P binding sites were characterized in brain nuclei of young (4-wk-old) and adult (16-wk-old) spontaneously hypertensive rats (SHR) and age-matched normotensive Wistar-Kyoto (WKY) control rats by quantitative autoradiography. Young SHR presented higher affinity constants (K/sub A/) than young WKY. The changes were restricted to locus coeruleus, the area postrema, the dorsal motor nucleus of the vagus, and to discrete areas located in lobes 9 and 10 of the vermis cerebelli of SHR. There were no differences in the maximal binding capacity (B/sub max/) except in the nucleus ambiguus where the B/sub max/ was lower than WKY. Conversely, the number of substance P binding sites was higher in the locus coeruleus, the nucleus tegmentalis dorsalis, the nucleus ambiguus, the dorsal motor nucleus of the vagus, the hypoglossal nucleus, the inferior olivary nucleus, and lobes 9 and 10 of the vermis cerebelli of adult SHR when compared with adult WKY. The results support the hypothesis of a role for brain substance P in blood pressure regulation and in genetic hypertension in rats.

  2. Influence of age on the relaxation induced by nifedipine in aorta from spontaneously hypertensive and Wistar Kyoto rats.

    PubMed

    Hernández, M C; Salaices, M; Arribas, S; Sánchez-Ferrer, C F; Marín, J

    1995-10-01

    1. Nifedipine induces relaxation in aortic segments from Wistar-Kyoto (WKY) and spontaneously hypertensive rats (SHR) of 5-week-, 3-month-, 6-month- and 1.5-year-old precontracted with 50 mM K+ or 0.1 microM noradrenaline (NA). 2. In WKY rat segments precontracted with K+, nifedipine relaxation was reduced at 1.5 years. However, in SHR segments, the greatest relaxation was observed at 1.5 years. The relaxation elicited by nifedipine in segments from WKY of 6-month and 1.5-year-old precontracted with NA was higher than that reached at 5-week- and 3-month-old. However, the relaxation induced in SHR of 6-month and 1.5-year-old was only higher than that obtained at 5-week-old. 3. Relaxations elicited by nifedipine in segments from WKY precontracted with K+ were smaller than those observed in age-matched SHR segments. 4. The endothelium positively and negatively modulates the relaxation to nifedipine in segments from SHR and WKY rats of different ages precontracted with K+, respectively. However, in segments of both strain precontracted with NA, endothelium removal did not alter the relaxations obtained at different ages. 5. These results suggest that the relaxation elicited by nifedipine: (1) depends on the strain, with a tendency to be greater in the hypertensive strain; (2) is negatively and positively modulated by endothelium in WKY and SHR, respectively, and (3) is influenced by age, and this influence depends on both the contractile agent and the strain.

  3. The hippocampus in spontaneously hypertensive rats: an animal model of vascular dementia?

    PubMed

    Sabbatini, Maurizio; Catalani, Assia; Consoli, Claudia; Marletta, Nunzio; Tomassoni, Daniele; Avola, Roberto

    2002-03-15

    Hypertension is a main risk factor for cerebrovascular disease, including vascular dementia. The present study was designed to evaluate if hypertension-dependent changes of the hippocampus of spontaneously hypertensive rats (SHR) of different ages were related with those occurring in vascular dementia. The hippocampus was chosen as the brain area involved in learning and memory. Systolic pressure was slightly increased in 2-month-old SHR in comparison with age-matched normotensive Wistar-Kyoto (WKY) rats and augmented progressively with age in SHR. No microanatomical changes were observed in the hippocampus of SHR of 2 months in comparison with age-matched WKY rats. A limited decrease of white matter volume was observed in 4-month-old SHR. In SHR of 6 months, a reduction of grey matter volume both in the CA1 subfield and in the dentate gyrus occurred. Evaluation of phosphorylated 200-kDa neurofilament immunoreactivity revealed a decreased immune reaction area in the CA1 subfield of 6-month-old SHR compared to age-matched WKY rats and no changes in the expression and localization of the dendritic marker microtubule associated protein (MAP)-2. In 6-month-old SHR, an increase of glial fibrillary acidic protein (GFAP)-expression was found by Western blot analysis. Immunohistochemistry revealed an increase in number (hyperplasia), but not in size of astrocytes. These findings indicate the occurrence of cytoskeletal breakdown and astroglial changes primarily in the CA1 subfield of the hippocampus of SHR of 6 months. The occurrence in the hippocampus of SHR of regressive changes and astroglial reaction similar to those occurring in neurodegenerative disorders with cognitive impairment suggests that they represent an animal model of vascular dementia.

  4. Attenuation of angiotensin type 2 receptor function in the rostral ventrolateral medullary pressor area of the spontaneously hypertensive rat

    PubMed Central

    Kawabe, Tetsuya; Iwasa, Masamitsu; Kawabe, Kazumi; Sapru, Hreday N.

    2016-01-01

    We hypothesized that blockade of angiotensin II type 2 receptors (AT2Rs) in the rostral ventrolateral medullary pressor area (RVLM) may elicit sympathoexcitatory responses which are smaller in hypertensive rats compared to normotensive rats. This hypothesis was tested in urethane-anesthetized, artificially ventilated male 14-week-old spontaneously hypertensive rats (SHR). Age-matched male Wistar-Kyoto rats (WKY) and Wistar rats were used as controls. PD123319 (AT2R antagonist) was microinjected into the RVLM and mean arterial pressure (MAP), heart rate (HR) and greater splanchnic nerve activity (GSNA) were recorded. Increases in MAP, HR and GSNA elicited by unilateral microinjections of PD123319 into the RVLM were significantly smaller in SHR when compared to those in WKY and Wistar rats. Unilateral microinjections of L-glutamate (L-Glu) into the RVLM elicited greater increases in MAP and GSNA in SHR compared to those in WKY. AT2R immunoreactivity was demonstrated in the RVLM neurons which were retrogradely labeled from the intermediolateral cell column (IML) of the spinal cord. These results indicate that AT2Rs are present on the RVLM neurons projecting to the IML and their blockade results in sympathoexcitatory responses. Activation of AT2Rs has an inhibitory influence in the RVLM and these receptors are tonically active. Attenuation of the function of AT2Rs in the RVLM may play a role in genesis and/or maintenance of hypertension in SHR. PMID:26818039

  5. 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.

  6. Altered turnover of polyphosphoinositides in the erythrocyte membrane of the spontaneously hypertensive rat

    SciTech Connect

    Koutouzov, S.; Marche, P.; Girard, A.; Meyer, P.

    1983-07-01

    The metabolism of inositol phospholipids of the erythrocyte membrane was compared in normotensive Wistar-Kyoto (WKY), spontaneously hypertensive (SHR), and stroke-prone SHR (SHR-SP) rats. This was performed on isolated ghost membranes by measuring the incorporation of /sup 32/P from ( gamma-/sup 32/P ) adenosine triphosphate (ATP) into the diphosphoinositides (DPI) and the triphosphoinositides (TPI) which were the only /sup 32/P-labeled phospholipids. /sup 32/P-labeling of TPI was altered in adult and 3-week-old SHR as well as in SHR-SP compared to WKY controls; the radioactivity associated with TPI in hypertensive rats was about 30% lower than that associated with TPI in age-matched normotensive controls. By contrast, the radioactivity associated with DPI was similar in both hypertensive and normotensive rats. Measurement of the phosphoinositide distribution in both SHR and WKY indicates that the change observed in /sup 32/P-TPI could not be accounted for by a reduced phosphatidylinositol content in SHR membrane. Measurement of the Mg/sup 2 +/-activated TPI-phosphomonoesterase and of the Ca/sup 2 +/-activated polyphosphoinositide phosphodiesterase activities did not show any significant difference between SHR and WKY. It thus appears that the altered phosphoinositide metabolism observed in hypertensive rats was a consequence of some alteration in the activity of kinases which are responsible for the conversion of phosphatidylinositol into DPI and TPI. These results also suggest that the defect in phosphoinositide metabolism observed in genetically hypertensive rats was not a consequence of the blood pressure elevation and could be related to the pathogenesis of hypertension.

  7. Alterations in the gut microbiota can elicit hypertension in rats.

    PubMed

    Adnan, Sareema; Nelson, James W; Ajami, Nadim J; Venna, Venugopal R; Petrosino, Joseph F; Bryan, Robert M; Durgan, David J

    2017-02-01

    Gut dysbiosis has been linked to cardiovascular diseases including hypertension. We tested the hypothesis that hypertension could be induced in a normotensive strain of rats or attenuated in a hypertensive strain of rats by exchanging the gut microbiota between the two strains. Cecal contents from spontaneously hypertensive stroke prone rats (SHRSP) were pooled. Similarly, cecal contents from normotensive WKY rats were pooled. Four-week-old recipient WKY and SHR rats, previously treated with antibiotics to reduce the native microbiota, were gavaged with WKY or SHRSP microbiota, resulting in four groups; WKY with WKY microbiota (WKY g-WKY), WKY with SHRSP microbiota (WKY g-SHRSP), SHR with SHRSP microbiota (SHR g-SHRSP), and SHR with WKY microbiota (SHR g-WKY). Systolic blood pressure (SBP) was measured weekly using tail-cuff plethysmography. At 11.5 wk of age systolic blood pressure increased 26 mmHg in WKY g-SHRSP compared with that in WKY g-WKY (182 ± 8 vs. 156 ± 8 mmHg, P = 0.02). Although the SBP in SHR g-WKY tended to decrease compared with SHR g-SHRSP, the differences were not statistically significant. Fecal pellets were collected at 11.5 wk of age for identification of the microbiota by sequencing the 16S ribosomal RNA gene. We observed a significant increase in the Firmicutes:Bacteroidetes ratio in the hypertensive WKY g-SHRSP, as compared with the normotensive WKY g-WKY (P = 0.042). Relative abundance of multiple taxa correlated with SBP. We conclude that gut dysbiosis can directly affect SBP. Manipulation of the gut microbiota may represent an innovative treatment for hypertension.

  8. Proper measurement of blood pressure and heart rate in SHRSP and WKY by an indirect volume-oscillometric method.

    PubMed

    Higashino, H; Simeonova, K; Lambev, I; Markov, M; Suzuki, A

    1995-12-01

    1. The effect of environmental temperature on the indirect measurement of rat blood pressure and heart rate was investigated with special reference to the tail arterial blood flow in both strains of SHRSP and WKY. 2. Very good correlations (r > 0.82, P < 0.05; t-test, 10 d.f.) were observed between the two values of systolic blood pressure or heart rate measured by a direct and an indirect method at environmental temperatures between 26 and 38 degrees C in SHRSP, and 34 and 38 degrees C in WKY, respectively. 3. When the temperature was elevated by 10 degrees C from 25 degrees C to 35 degrees C, the regional blood flow in the tail artery increased by 52-69%, sufficient to detect a blood flow increase by the indirect method. 4. These data showed that the best way to measure the accurate blood pressure and heart rate in both strains of SHRSP and WKY by the indirect volume-oscillometric method was to hold the rats at 34-36 degrees C for 5 min.

  9. Decreased norepinephrine content in the medulla oblongata in severely hypertensive rats.

    PubMed

    Takami, T; Ito, H; Suzuki, T

    1993-03-01

    1. To clarify possible abnormalities in catecholamines in the medulla oblongata in relation to severe hypertension, the authors measured changes in catecholamine levels in the medulla oblongata of malignant stroke-prone spontaneously hypertensive rats (M-SHRSP). Effects of the adrenal medullae and peripheral nerves were ruled out by adrenal demedullation and chemical sympathectomy. 2. The level of norepinephrine in the medulla oblongata was significantly lower in untreated M-SHRSP than in untreated WKY (control) rats at 10 weeks of age. Further, it was significantly lower in treated M-SHRSP than in the treated WKY group at both 6 and 10 weeks of age. The level of epinephrine in 6 week old treated M-SHRSP was significantly higher than that in age-matched treated WKY, but no other differences were observed in terms of epinephrine content. There were no age- or treatment-related differences in dopamine levels in the medullar oblongata. 3. Since norepinephrine has an inhibitory effect on blood pressure elevation in the nucleus tractus solitarii (NTS) in the medulla oblongata, the suppression of negative feedback due to a decrease in the activity of inhibitory neurons in the medulla oblongata appears to be involved in the development and progression of severe hypertension in M-SHRSP.

  10. Anxiety- and depressive-like profiles during early- and mid-adolescence in the female Wistar Kyoto rat.

    PubMed

    D'Souza, Deepthi; Sadananda, Monika

    2017-02-01

    Approaches for the development of preclinical models of depression extensively use adult and male animals owing to the discrepancies arising out of the hormonal flux in adult females and adolescents during attainment of puberty. Thus the increased vulnerability of females towards clinical depression and anxiety-related disorders remains incompletely understood. Development of clinical models of depression in adolescent females is essential in order to evolve effective treatment strategies for adolescent depression. In the present study, we have examined the anxiety and depressive-like profiles in a putative animal model of childhood depression, the Wistar Kyoto (WKY) rat, during early adolescence (∼postnatal day 30) and mid-adolescence (∼postnatal day 40). Female adolescent WKY rats, tested on a series of behavioural tests modelling anxiety- and depressive-like behaviours with age-matched Wistars as controls, demonstrated marked differences during early adolescence in a strain- and age-specific manner. Anxiety indices were obtained from exposure to the elevated plus maze, where social communication vide 50-kHz ultrasonic vocalizations was also assessed, while immobility and other parameters in the forced swim test were screened for depressive-like profiles. Sucrose preference, used as a measure of anhedonia in animals, was lower in WKYs at both ages tested and decreased with age. Anxiety-related behaviours were prominent in WKY rats only during early adolescence. WKY female rats are anxious during early adolescence and exhibit anhedonia as a core symptom of depression during early- and mid-adolescence, thus indicating that inclusion of female animals in preclinical trials is essential and will contribute to gender-based approaches to diagnosis and treatment of adolescent depression in females.

  11. Effect of melatonin on blood pressure and nitric oxide generation in rats with metabolic syndrome.

    PubMed

    Klimentova, J; Cebova, M; Barta, A; Matuskova, Z; Vrankova, S; Rehakova, R; Kovacsova, M; Pechanova, O

    2016-10-24

    Melatonin, a multitasking indolamine, seems to be involved in a variety of physiological and metabolic processes via both receptor-mediated and receptor-independent mechanisms. The aim of our study was to find out whether melatonin can affect blood pressure (BP), nitric oxide synthase (NOS) activity, eNOS and nNOS protein expressions in rats with metabolic syndrome (SHR/cp). Rats were divided into four groups: 6-week-old male WKY andSHR/cp and age-matched WKY and SHR/cp treated with melatonin (10 mg/kg/day) for 3 weeks. BP was measured by tail-cuff plethysmography. NOS activity, eNOS and nNOS protein expressions were determined in the heart, aorta, brain cortex and cerebellum. MT(1) receptors were analyzed in the brain cortex and cerebellum. In SHR/cp rats, BP was decreased after melatonin treatment. In the same group, melatonin did not affect NOS activity and eNOS protein expression in the heart and aorta, while it increased both parameters in the brain cortex and cerebellum. Interestingly, melatonin elevated MT1 protein expression in the cerebellum. Neuronal NOS protein expression was not changed within the groups. In conclusion, increased NOS activity/eNOS upregulation in particular brain regions may contribute partially to BP decrease in SHR/cp rats after melatonin treatment. Participation of MT(1) receptors in this melatonin action may be supposed.

  12. Effects of aglycone genistein in a rat experimental model of postmenopausal metabolic syndrome.

    PubMed

    Bitto, Alessandra; Altavilla, Domenica; Bonaiuto, Antonio; Polito, Francesca; Minutoli, Letteria; Di Stefano, Vincenzo; Giuliani, Daniela; Guarini, Salvatore; Arcoraci, Vincenzo; Squadrito, Francesco

    2009-03-01

    Genistein aglycone, a soy derived isoflavone, has been demonstrated to be effective in reducing cardiovascular risk in postmenopausal women. We therefore investigated its effects in an experimental model of postmenopausal metabolic syndrome. Female spontaneously hypertensive obese rats (SHROB, n=40), a genetic model of syndrome X, and age-matched Wistar Kyoto (WKY, n=40) rats were used. A group of SHROB (n=20) and WKY (n=20) animals were ovariectomized (OVX). Four weeks after surgery all animals were randomized to receive either genistein (54 mg/human equivalent dose/day for 4 weeks), or vehicle. Body weight, food intake, systolic blood pressure (SBP), heart rate, plasma glucose, insulin resistance (HOMA-IR), total plasma cholesterol and triglycerides, and uterine weights were studied. Furthermore, we investigated acetylcholine- and sodium nitroprusside-induced relaxation of aortic rings as well as NG-L-arginine (L-NMA: 10-100 mM) induced vasoconstriction in phenylephrine-precontracted aortic segments. Liver expression of the peroxisome proliferator-activated receptor alpha (PPARA and gamma (PPARG was also assessed. OVX animals had a slight increase in SBP, body weight, insulin resistance, and plasma cholesterol. OVX-SHROB rats showed also impaired endothelial responses, blunted L-NMA induced contraction (L-NMA 100 mM, WKY=2.2+/-0.3 g/mg tissue; OVX-SHROB=1.1+/-0.4 g/mg tissue). Genistein treatment decreased SBP and plasma lipids, ameliorated endothelial dysfunction and insulin resistance, increased HDL cholesterol, and enhanced liver expression of PPARA and PPARG. Our data suggest that genistein is effective in ameliorating cardiovascular profiles in an experimental model of postmenopausal metabolic syndrome, attenuating the features of this disease. The effects of genistein are likely mediated by PPARA and PPARG receptors. This evidence would support the rationale for some pilot clinical trials using genistein in postmenopausal women affected by metabolic

  13. 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

  14. Beneficial effects of losartan on vascular injury induced by advanced glycosylation end products and their receptors in spontaneous hypertension rats.

    PubMed

    Zhu, Wei-Wei; Liu, Xue-Ping; Wu, Nan; Zhao, Ting-Ting; Zhao, Yong; Zhang, Jie; Shao, Jian-Hua

    2007-10-01

    This study was designed to explore the role of losartan, an angiotensin II receptor blocker, in hypertensive injuries of blood vessels and the potential mechanisms related to the vascular advanced glycosylation end product (AGE)/receptor (RAGE) system, oxidative stress and endothelial proinflammatory factors. Spontaneously hypertensive rats (SHR) were employed for our study, and age-matched Wistar-Kyoto rats (WKY) were used for control experiments. After losartan treatment for 12 weeks, we observed by immunofluorescence that the vascular AGE level in the losartan group was significantly lower than that of the SHR group and that the vascular mRNA expression of RAGE, NF-kappaB, NADPH oxidase p47phox and ET-1, as detected by RT-PCR, was significantly lower in losartan group than in the SHR group. Meanwhile, we found that the expression of RAGE and NF-kappaB proteins in the losartan group and the WKY group was remarkably lower than that of the SHR group. Compared with the SHR group, the activities of plasma superoxide dismutase (SOD) and glutathione peroxidase (GSH-PX) and the NO level were robustly increased, while the plasma malondialdehyde (MDA) and ET-1 were substantially reduced. These findings suggest that losartan decreases the vascular AGE level, suppresses RAGE and NF-kappaB activation, and enhances the antioxidant capacity thereby improving the endothelial function, which induce hypertensive vascular remodeling.

  15. Effects of treppe and calcium on intracellular calcium and function in the failing heart from the spontaneously hypertensive rat.

    PubMed

    Brooks, W W; Bing, O H; Litwin, S E; Conrad, C H; Morgan, J P

    1994-09-01

    We studied functional and intracellular calcium responses to treppe and extracellular calcium in spontaneously hypertensive rat (SHR) hearts during the transition from compensated pressure overload to failure. Intracellular calcium was measured using aequorin, a bioluminescent Ca2+ indicator. Experiments were performed with intact, isovolumically contracting, buffer-perfused hearts from three rat groups: (1) aging SHR with evidence of heart failure (SHR-F), (2) age-matched SHR with no evidence of heart failure (SHR-NF), and (3) age-matched normotensive Wistar-Kyoto (WKY) rats. In each experiment, left ventricular pressure and intracellular calcium transients were simultaneously recorded. Hearts were studied at 30 degrees C and paced at a rate of 1.6 Hz while being perfused with oxygenated Krebs-Henseleit solution (95% O2/5% CO2) at 100 mm Hg. At the baseline state, peak systolic pressure was greatest in the SHR-NF group and lowest in the SHR-F group. Peak and resting [Ca2+]i were not significantly different among groups; however, the calcium transient was prolonged in the SHR-NF and SHR-F groups. With increasing perfusate [Ca2+]o from 0.5 to 3.0 mmol/L, the relative increases in peak [Ca2+]i and peak systolic pressure were similar among groups. When stimulation rate was increased from 1.6 to 2.0, 2.4, 2.8, and 3.2 Hz, peak [Ca2+]i, peak systolic pressure, and +/- dP/dt fell in SHR-F hearts. Peak systolic pressure decreased in the SHR-NF group at rates above 2.4 Hz but did not decline in the WKY group. Peak [Ca2+]i increased in the WKY and SHR-NF groups with increasing heart rates. Peak systolic pressure did not fall significantly in the WKY group at any heart rate. Elevation of diastolic [Ca2+]i and/or calcium transient and pressure alternans were present in 8 of 13 SHR-F hearts at the highest stimulation rate, findings that were absent in both the WKY and SHR-NF hearts. We conclude the following: (1) Under baseline conditions, depressed contractile function of

  16. Effects of d-amphetamine on short- and long-term memory in spontaneously hypertensive, Wistar-Kyoto and Sprague-Dawley rats.

    PubMed

    Meneses, A; Ponce-Lopez, T; Tellez, R; Gonzalez, R; Castillo, C; Gasbarri, A

    2011-01-01

    Diverse studies indicate that the attention deficit hyperactivity disorder (ADHD) is associated with alterations in encoding processes, including working or short-term memory. Some ADHD dysfunctional domains are reflected in the spontaneously hypertensive rat (SHR). Here SHR-saline group showed significantly poor STM and LTM relative to SD and WKY saline rats. SD and WKY rats treated with d-amphetamine displayed better STM and LTM, compared to SD-vehicle, WKY-vehicle or SHR-d-amphetamine groups.

  17. Postural finger tremor exhibited by Parkinson patients and age-matched subjects.

    PubMed

    Palmer, S S; Hutton, J T

    1995-09-01

    Physiological correlates of postural tremor of the finger seen in Parkinson's disease patients are different from those seen in age-matched control subjects. A significant correlation between the spectral peak of acceleration and the spectral peak of rectified electromyographic activity from the muscle responsible for finger extension was found in Parkinson's disease patients. This correlation was not seen in age-matched control subjects. Any neural drive imposed on the motoneuron pool from supraspinal levels would enhance the electromyographic activity. Likewise, any feedback effects via spinal stretch reflexes or supraspinal stretch responses would be mediated through the motoneuron pool and electromyographic activity. The results of this research support the theory that Parkinson tremor is a centrally driven rhythm that may be influenced by feedback effects, whereas physiological tremor is due to a complex interaction of central, feedback, and mechanical effects.

  18. Genetic architecture of Wistar-Kyoto rat and spontaneously hypertensive rat substrains from different sources.

    PubMed

    Zhang-James, Yanli; Middleton, Frank A; Faraone, Stephen V

    2013-07-02

    The spontaneously hypertensive rat (SHR) has been widely used as a model for studies of hypertension and attention deficit/hyperactivity disorder. The inbred Wistar-Kyoto (WKY) rat, derived from the same ancestral outbred Wistar rat as the SHR, are normotensive and have been used as the closest genetic control for the SHR, although the WKY has also been used as a model for depression. Notably, however, substantial behavioral and genetic differences among the WKY substrains, usually from the different vendors and breeders, have been observed. These differences have often been overlooked in prior studies, leading to inconsistent and even contradictory findings. The complicated breeding history of the SHR and WKY rats and the lack of a comprehensive understanding of the genetic background of different commercial substrains make the selection of control rats a daunting task, even for researchers who are mindful of their genetic heterogeneity. In this study, we examined the genetic relationship of 16 commonly used WKY and SHR rat substrains using genome-wide SNP genotyping data. Our results confirmed a large genetic divergence and complex relationships among the SHR and WKY substrains. This understanding, although incomplete without the genome sequence, provides useful guidance in selecting substrains and helps to interpret previous reports when the source of the animals was known. Moreover, we found two closely related, yet distinct WKY substrains that may provide novel opportunities in modeling psychiatric disorders.

  19. Classical and instrumental conditioning of eyeblink responses in Wistar-Kyoto and Sprague-Dawley rats.

    PubMed

    Ricart, Thomas M; Jiao, Xilu; Pang, Kevin C H; Beck, Kevin D; Servatius, Richard J

    2011-01-01

    Wistar-Kyoto (WKY) rats, an animal model of anxiety vulnerability, acquire lever-press avoidance faster than outbred Sprague-Dawley (SD) rats. Faster avoidance acquisition may reflect an inherent ability to acquire cue-outcome associations, response-outcome associations or both. To evaluate cue-outcome learning, acquisition of classically conditioned eyeblink response was compared in SD and WKY rats using a delay-type paradigm (500-ms conditioned stimulus (CS) coterminating with a 10-ms unconditional stimulus (US)). WKY rats demonstrated enhanced classical conditioning, with both faster acquisition and greater asymptotic performance in delay-type training than SD rats. To evaluate response-outcome learning, separate SD and WKY rats were given control over US delivery through imposition of an omission contingency into delay-type training (emitting a conditioned response (CR) prevented delivery of the US). The schedule of US delivery derived by these rats became the training regimen for a separate group of SD and WKY rats, yoked within strain. In SD rats, no differences in acquisition were detected between those given control over US delivery and those trained with the same partial reinforcement schedule. Acquisition rates of those WKY rats with control exceeded those trained with a yoked-schedule of US presentation. Collectively, WKY rats exhibit enhanced classical conditioning and sensitivity to schedules of reinforcement compared to outbred SD rats. Anxiety vulnerability, in particular inhibited temperament, may be traced to active processes in the prediction and control of aversive events.

  20. 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.

  1. 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.

  2. A proteomic study of protein variation between osteopenic and age-matched control bone tissue.

    PubMed

    Chaput, Christopher D; Dangott, Lawrence J; Rahm, Mark D; Hitt, Kirby D; Stewart, Donald S; Wayne Sampson, H

    2012-05-01

    The focus of this study was to identify changes in protein expression within the bone tissue environment between osteopenic and control bone tissue of human femoral neck patients with osteoarthritis. Femoral necks were compared from osteopenic patients and age-matched controls. A new method of bone protein extraction was developed to provide a swift, clear view of the bone proteome. Relative changes in protein expression between control and osteopenic samples were quantified using difference gel electrophoresis (DIGE) technology after affinity chromatographic depletion of albumin and IgG. The proteins that were determined to be differentially expressed were identified using standard liquid chromatography mass spectrometry (LC/MS/MS) and database searching techniques. In order to rule out blood contamination, blood from age-matched osteoporotic, osteopenic and controls were analyzed in a similar manner. Image analysis of the DIGE gels indicated that 145 spots in the osteopenic bone samples changed at least ± 1.5-fold from the control samples (P < 0.05). Three of the proteins were identified by LC/MS/MS. Of the proteins that increased in the osteopenic femurs, two were especially significant: carbonic anhydrase I and phosphoglycerate kinase 1. Apolipoprotein A-I was the most prominent protein that significantly decreased in the osteopenic femurs. The blood samples revealed no significant differences between groups for any of these proteins. In conclusion, carbonic anhydrase I, phosphoglycerate kinase 1 and apolipoprotein A-I appeared to be the most significant variations of proteins in patients with osteopenia and osteoarthritis.

  3. Autism-related behavioral phenotypes in an inbred rat substrain.

    PubMed

    Zhang-James, Yanli; Yang, Li; Middleton, Frank A; Yang, Lina; Patak, Jameson; Faraone, Stephen V

    2014-08-01

    Behavioral and genetic differences among Wistar-Kyoto (WKY) rats from different vendors and different breeders have long been observed, but generally overlooked. In our prior work, we found that two closely related WKY substrains, the WKY/NCrl and WKY/NHsd rats, differ in a small percentage of their genome which appeared to be highly enriched for autism risk genes. Although both substrains have been used widely in studies of hypertension, attention deficit/hyperactivity disorder (ADHD) and depression, they have not been tested for any autism-related behavioral phenotypes. Furthermore, these two substrains have often been used interchangeably in previous studies; no study has systematically examined the phenotypic differences that could be attributed by their small yet potentially meaningful genetic differences. In this paper we compared these two substrains on a battery of neurobehavioral tests. Although two substrains were similar in locomotor activity, WKY/NCrl rats were significantly different from WKY/NHsd rats in the elevated plus maze test, as well as measures of social interaction and ultrasonic vocalization. These strains were also compared with Sprague Dawley (SD) rats, a common outbred strain, and spontaneous hypertensive rats (SHR), an inbred rat model for ADHD and hypertension, which were derived from the same ancestor strain as the WKY strains. Our behavioral findings suggest that WKY/NCrl rats may be useful as a model autism spectrum disorders due to their lower social interest, lower ultrasonic vocalization and higher anxiety levels when WKY/NHsd rats are used as the control strain. Given the small genetic difference between the two inbred substrains, future studies to identify the exact gene and sequence variants that differ between the two may be useful for identifying the genetic mechanisms underlying these behaviors.

  4. Effects of aging and hypertension on the participation of endothelium-derived constricting factor (EDCF) in norepinephrine-induced contraction of rat femoral artery.

    PubMed

    Líšková, Silvia; Silvia, Líšková; Petrová, Miriam; Miriam, Petrová; Karen, Petr; Petr, Karen; Kuneš, Jaroslav; Jaroslav, Kuneš; Zicha, Josef; Josef, Zicha

    2011-09-30

    Endothelium-dependent contraction elicited by high concentrations of acetylcholine was described in hypertensive as well as in aged normotensive rats. The contribution of endothelium-derived constricting factor (EDCF) to norepinephrine-induced contraction is still unknown. We aimed to compare EDCF participation to norepinephrine-induced arterial contraction in spontaneously hypertensive rats (SHR) and aged normotensive Wistar-Kyoto (WKY) rats. Femoral arteries from either adult (7-months-old) or aged (14-months-old) animals were placed in myograph and norepinephrine-induced concentration-response curves were recorded under control conditions and in the presence of indomethacin (cyclooxygenase inhibitor, 10(-5) mol/l) or L-NNA (NO synthase inhibitor, 10(-4) mol/l) or both. Norepinephrine-induced concentration-response curve was enhanced in SHR compared to WKY rats, but concentration-response curve of aged WKY rats was similar to those of adult SHR. Cyclooxygenase inhibition largely attenuated concentration-response curves in all groups. However, this effect was greater in aged WKY rats and adult SHR compared to adult WKY rats. NO synthase inhibition augmented norepinephrine-induced contraction in arteries of adult WKY rats, but not in arteries from aged WKY rats or adult SHR. The combined administration of L-NNA and indomethacin had no additive effects on concentration-response curves. EDCF contribution to norepinephrine-induced contractions of arteries was considerably greater in adult SHR (80±3%) and aged WKY rats (86±2%) compared to adult WKY rats (35±10%). The inhibition of NO synthase augmented EDCF contribution to norepinephrine-induced contraction only in arteries from adult WKY rats (76±9%). We conclude that EDCF contribution to norepinephrine-induced contraction of conduit arteries is similarly enhanced in adult hypertensive and aged normotensive rats.

  5. Comparison of Brachial Artery Vasoreactivity in Elite Power Athletes and Age-Matched Controls

    PubMed Central

    Welsch, Michael A.; Blalock, Paul; Credeur, Daniel P.; Parish, Tracie R.

    2013-01-01

    Elite endurance athletes typically have larger arteries contributing to greater skeletal muscle blood flow, oxygen and nutrient delivery and improved physical performance. Few studies have examined structural and functional properties of arteries in power athletes. Purpose To compare the size and vasoreactivity of the brachial artery of elite power athletes to age-matched controls. It was hypothesized brachial artery diameters of athletes would be larger, have less vasodilation in response to cuff occlusion, but more constriction after a cold pressor test than age-matched controls. Methods Eight elite power athletes (age = 23±2 years) and ten controls (age = 22±1 yrs) were studied. High-resolution ultrasonography was used to assess brachial artery diameters at rest and following 5 minutes of forearm occlusion (Brachial Artery Flow Mediated Dilation = BAFMD) and a cold pressor test (CPT). Basic fitness measures included a handgrip test and 3-minute step test. Results Brachial arteries of athletes were larger (Athletes 5.39±1.51 vs. Controls: 3.73±0.71 mm, p<0.05), had greater vasodilatory (BAFMD%: Athletes: 8.21±1.78 vs. Controls: 5.69±1.56%) and constrictor (CPT %: Athletes: -2.95±1.07 vs. Controls: −1.20±0.48%) responses, compared to controls. Vascular operating range (VOR = Peak dilation+Peak Constriction) was also greater in athletes (VOR: Athletes: 0.55±0.15 vs. Controls: 0.25±0.18 mm, p<0.05). Athletes had superior handgrip strength (Athletes: 55.92±17.06 vs. Controls: 36.77±17.06 kg, p<0.05) but similar heart rate responses at peak (Athletes: 123±16 vs. Controls: 130±25 bpm, p>0.05) and 1 minute recovery (Athletes: 88±21 vs. Controls: 98±26 bpm, p>0.05) following the step test. Conclusion Elite power athletes have larger brachial arteries, and greater vasoreactivity (greater vasodilatory and constrictor responses) than age-matched controls, contributing to a significantly greater VOR. These data extend the existence of an

  6. Down-regulation of endothelin receptors in the ventrolateral medulla of spontaneously hypertensive rats

    SciTech Connect

    Gulati, A.; Rebello, S. )

    1991-01-01

    The binding of ({sup 125}I) sarafotoxin 6b (SRT 6b) and ({sup 125}I) endothelin-1 (ET-1) to endothelin (ET) receptors of neuronal membranes prepared from cerebral cortex and ventrolateral medulla of 8 week old spontaneously hypertensive (SHR) and normotensive Wistar-Kyoto (WKY) rats was determined. ({sup 125}I) SRT 6b bound to the membranes of cerebral cortex and ventrolateral medulla at a single high affinity site. The binding of ({sup 125}I) SRT 6b in the cerebral cortex was found to be similar in SHR and WKY rats. However, in the ventrolateral medulla ({sup 125}I) SRT 6b binding was found to be significantly lower in SHR as compared to WKY rats. The decreased binding was due to decrease (48%) in the B{sub max} values in SHR rats as compared to WKY rats. The K{sub d} values were similar in SHR and WKY rats. ({sup 125}I) ET-1 also bound to the membranes of cerebral cortex and ventrolateral medulla at a single high affinity site. The binding of ({sup 125}I) ET-1 in the cerebral cortex was found to be similar in SHR and WKY rats. However, in the ventrolateral medulla ({sup 125}I) ET-1 binding was found to be significantly lower in SHR as compared to WKY rats. The decreased binding was due to 36% decrease in the B{sub max} values in SHR rats as compared to WKY rats. The K{sub d} values were similar in SHR and WKY rats. It is concluded that the population of ET receptors is less in the ventrolateral medulla of SHR rats and may be contributing to the regulation of blood pressure.

  7. Nimodipine disposition and haemodynamic effects in patients with cirrhosis and age-matched controls.

    PubMed Central

    Gengo, F M; Fagan, S C; Krol, G; Bernhard, H

    1987-01-01

    Six biopsy proven cirrhotics and five age-matched controls (mean 55.3 vs 52.4 years) were randomly given single 60 mg p.o. and 30 mg s.l. doses of nimodipine. Serum concentrations and blood pressure were measured regularly over the subsequent 24 h period. The clearance of nimodipine was reduced in the patients with cirrhosis. Apparent oral clearance of nimodipine in the cirrhotic group was significantly lower than that observed in the normal group (187 +/- 163 l h-1 vs 469.6 +/- 198.4 l h-1, P less than 0.01). There were no significant changes in mean arterial pressure (MAP) in the normal subjects. There were, however, significant reductions in MAP following oral nimodipine in the cirrhotics. These reductions were significantly related to nimodipine concentrations in individual patients (P less than 0.05). PMID:3814462

  8. Rapid avoidance acquisition in Wistar-Kyoto rats.

    PubMed

    Servatius, R J; Jiao, X; Beck, K D; Pang, K C H; Minor, T R

    2008-10-10

    The relationship between trait stress-sensitivity, avoidance acquisition and perseveration of avoidance was examined using male Wistar-Kyoto (WKY) and Sprague-Dawley (SD) rats. Behavior in an open field was measured prior to escape/avoidance (E/A) acquisition and extinction. E/A was assessed in a discrete trial lever-press protocol. The signal-shock interval was 60s with subsequent shocks delivered every 3s until a lever-press occurred. A 3-min flashing light safety signal was delivered contingent upon a lever-press (or failure to respond in 5 min). WKY rats displayed phenotypic low open field activity, but were clearly superior to SD rats in E/A performance. As avoidance responses were acquired and reached asymptotic performance, SD rats exhibited "warm up", that is, SD rats rarely made avoidance responses on the initial trial of a session, even though later trials were consistently accompanied with avoidance responses. In contrast, WKY rats did not show the "warm up" pattern and avoided on nearly all trials of a session including the initial trial. In addition to the superior acquisition of E/A, WKY rats demonstrated several other avoidance features that were different from SD rats. Although the rates of nonreinforced intertrial responses (ITRs) were relatively low and selective to the early safety period, WKY displayed more ITRs than SD rats. With removal of the shocks extinction was delayed in WKY rats, likely reflecting their nearly perfect avoidance performance. Even after extensive extinction, first trial avoidance and ITRs were evident in WKY rats. Thus, WKY rats have a unique combination of trait behavioral inhibition (low open field activity and stress sensitivity) and superior avoidance acquisition and response perseveration making this strain a good model to understand anxiety disorders.

  9. *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 ...

  10. Calcium and vitamin D metabolism in spontaneously hypertensive rats

    SciTech Connect

    Hsu, Chen Hsing; Yang, Chweishiun; Patel, S.R.; Stevens, M.G. )

    1987-10-01

    The authors have studied the effect of dietary vitamin D restriction on serum levels of vitamin D metabolites, measured by radioreceptor assay and radioimmunoassay in spontaneously hypertensive rats (SHR) and normotensive Wistar-Kyoto rats (WKY). Both WKY and SHR were fed a vitamin D-deficient or a vitamin D-supplemented diet beginning at 4 wk of age. In vitamin D-supplemented animals, the serum 1,25-dihydroxycholecalciferol (1,25(OH){sub 2}D{sub 3}) concentration of WKY was similar to the level of SHR. Plasma calcium concentration was not different between WKY and SHR. In animals fed a vitamin D-deficient diet, the serum concentration of 1,25-(OH){sub 2}D{sub 3} of SHR was significantly lower than that of WKY. Plasma 25-hydroxycholecalciferol level was markedly decreased in both WKY and SHR. The SHR, but not the WKY, developed hypocalcemia. Despite hypocalcemia, fasting urinary Ca{sup 2+} excretion of SHR exceeded that of WKY. They conclude that the lower 1,25(OH){sub 2}D{sub 3} level in SHR fed a vitamin D-deficient diet may be due to a defect in the synthesis of 1,25(OH){sub 2}D{sub 3}. The low level of 1,25(OH){sub 2}D{sub 3} is associated with renal wasting of calcium and hypocalcemia in SHR.

  11. 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...

  12. Effect of treatment with choline alphoscerate on hippocampus microanatomy and glial reaction in spontaneously hypertensive rats.

    PubMed

    Tomassoni, Daniele; Avola, Roberto; Mignini, Fiorenzo; Parnetti, Lucilla; Amenta, Francesco

    2006-11-20

    The influence of long term treatment with choline alphoscerate on microanatomy of hippocampus and glial reaction was assessed in spontaneously hypertensive rats (SHR) used as an animal model of cerebrovascular disease. Choline alphoscerate is a cholinergic precursor, which has shown to be effective in countering cognitive symptoms in forms of dementia disorders of degenerative, vascular or combined origin. Male spontaneously hypertensive rats (SHR) aged 6 months and age-matched normotensive Wistar-Kyoto (WKY) rats were treated for 8 weeks with an oral daily dose of 100 mg/kg of choline alphoscerate, 285 mg/kg of phosphatidylcholine (lecithin) or vehicle. On the hippocampus of different animal groups, nerve cell number and GFAP-immunoreactive astrocytes were assessed by neuroanatomical, immunochemical and immunohistochemical techniques associated with quantitative analysis. Treatment with choline alphoscerate countered nerve cell loss and glial reaction primarily in the CA1 subfields and in the dentate gyrus of the hippocampus of SHR. Phosphatidylcholine did not affect hypertension-dependent changes in hippocampal microanatomy. Both compounds did not affect blood pressure values in SHR. These data suggest that choline alphoscerate may play a role in the countering hippocampal changes induced by cerebrovascular involvement. The observation that treatment with choline alphoscerate attenuates the extent of glial reaction in the hippocampus of SHR suggests also that the compound may afford neuroprotection in this animal model of vascular brain damage.

  13. Cardiovascular function is better in veteran football players than age-matched untrained elderly healthy men.

    PubMed

    Schmidt, J F; Andersen, T R; Andersen, L J; Randers, M B; Hornstrup, T; Hansen, P R; Bangsbo, J; Krustrup, P

    2015-02-01

    The aim of the study was to determine whether lifelong football training may improve cardiovascular function, physical fitness, and body composition. Our subjects were 17 male veteran football players (VPG; 68.1 ± 2.1 years) and 26 healthy age-matched untrained men who served as a control group (CG; 68.2 ± 3.2 years). Examinations included measurements of cardiac function, microvascular endothelial function [reactive hyperemic index (RHI)], maximum oxygen uptake (VO2max), and body composition. In VPG, left ventricular (LV) end-diastolic volume was 20% larger (P < 0.01) and LV ejection fraction was higher (P < 0.001). Tissue Doppler imaging revealed an augmented LV longitudinal displacement, i.e., LV shortening of 21% (P < 0.001) and longitudinal 2D strain was 12% higher (P < 0.05), in VPG. In VPG, resting heart rate was lower (6 bpm, P < 0.05), and VO2max was higher (18%, P < 0.05). In addition, RHI was 21% higher (P < 0.05) in VPG. VPG also had lower body mass index (P < 0.05), body fat percentage, total body fat mass, android fat percentage, and gynoid fat percentage (all P < 0.01). Lifelong participation in football training is associated with better LV systolic function, physical fitness, microvascular function, and a healthier body composition. Overall, VPG have better cardiovascular function compared with CG, which may reduce their cardiovascular morbidity and mortality.

  14. Congenic strain differences of renal malformations in ACI/Mna rats by introgression of the chromosomal region of BUF/Mna rats containing Pur1.

    PubMed

    Matsuyama, Mutsushi; Haneda, Chiemi; Kato, Kazuo

    2013-08-01

    The ACI rats developed hereditary renal malformations including agenesis and hydronephrosis at moderate penetrance. During construction of a variety of congenic strains based on ACI/Mna (ACI), BUF/Mna (BUF), and WKY/NCrj (WKY) rats, we found that the renal malformations were significantly suppressed by introgression of a segment of chromosome 13 of BUF rats containing Pur1 locus. It is plausible that this region contain a modifier locus influencing development of renal malformations.

  15. 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...

  16. 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 ...

  17. Developmental Level and Psychopathology: Comparing Children with Developmental Delays to Chronological and Mental Age Matched Controls

    PubMed Central

    Caplan, Barbara; Neece, Cameron L.; Baker, Bruce L.

    2015-01-01

    Children with developmental delays (DD) are at heightened risk for developing clinically significant behavioral and emotional difficulties as compared to children with typical development (TD). However, nearly all studies comparing psychopathology in youth with DD employ TD control groups of the same chronological age (CA). It is unclear, then, whether the heightened symptomology found in age-matched children with DD is beyond what would be expected given their developmental level. The present study assessed rates of behavior problems and mental disorder in 35 children with DD at age 9 years. These were compared with rates from 35 children with TD matched for CA at age 9 and also earlier rates for these same children at age 6, when matched for mental age (MA). Children with DD had significantly more behavior problems in 7 of the 17 scales of the CBCL when compared to TD children matched for CA, and 6 of 17 scales when compared to the MA-matched group. Rates of meeting DSM-IV criteria for a psychiatric disorder were significantly higher in the DD group than both the CA- and MA-matched TD groups for three and four, respectively, of the seven diagnoses examined. Descriptively, the mean ratings for all variables assessed were higher for the DD group than both TD comparison groups, with the exception of the Anxious/Depressed scale of the CBCL. These findings validate the heightened risk for clinically significant behavior problems and mental disorders in youth with DD above and beyond their developmental functioning. PMID:25498740

  18. ABCB1 genotypes and haplotypes in patients with dementia and age-matched non-demented control patients

    PubMed Central

    Frankfort, Suzanne V; Doodeman, Valerie D; Bakker, Remco; Tulner, Linda R; van Campen, Jos PCM; Smits, Paul HM; Beijnen, Jos H

    2006-01-01

    Amyloid β is an in vitro substrate for P-glycoprotein (P-gp), an efflux pump at the blood brain barrier (BBB). The Multi Drug Resistance (ABCB1) gene, encoding for P-gp, is highly polymorphic and this may result in a changed function of P-gp and may possibly interfere with the pathogenesis of Alzheimer's disease. This study investigates to what extent ABCB1 Single Nucleotide Polymorphisms (SNPs; C1236T in exon 12, G2677T/A in exon 21 and C3435T in exon 26) and inferred haplotypes exist in an elderly population and if these SNPs and haplotypes differ between patients with dementia and age-matched non-demented control patients. ABCB1 genotype, allele and haplotype frequencies were neither significantly different between patients with dementia and age-matched controls, nor between subgroups of different types of dementia nor age-matched controls. This study shows ABCB1 genotype frequencies to be comparable with described younger populations. To our knowledge this is the first study on ABCB1 genotypes in dementia. ABCB1 genotypes are presently not useful as a biomarker for dementia, as they were not significantly different between demented patients and age-matched control subjects. PMID:16999857

  19. 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…

  20. Redox-Sensitive Oxidation and Phosphorylation of PTEN Contribute to Enhanced Activation of PI3K/Akt Signaling in Rostral Ventrolateral Medulla and Neurogenic Hypertension in Spontaneously Hypertensive Rats

    PubMed Central

    Wu, Kay L.H.; Wu, Chiung-Ai; Wu, Chih-Wei; Chan, Samuel H.H.; Chang, Alice Y.W.

    2013-01-01

    Abstract Aims: The activity of phosphoinositide 3-kinase (PI3K)/serine/threonine protein kinase (Akt) is enhanced under hypertension. The phosphatase and tensin homolog deleted on chromosome 10 (PTEN) is a negative regulator of PI3K signaling, and its activity is redox-sensitive. In the rostral ventrolateral medulla (RVLM), which is responsible for the maintenance of blood pressure, oxidative stress plays a pivotal role in neurogenic hypertension. The present study evaluated the hypothesis that redox-sensitive inactivation of PTEN results in enhanced PI3K/Akt signaling in RVLM, leading to neurogenic hypertension. Results: Compared to age-matched normotensive Wistar-Kyoto (WKY) rats, PTEN inactivation in the form of oxidation and phosphorylation were greater in RVLM of spontaneously hypertensive rats (SHR). PTEN inactivation was accompanied by augmented PI3K activity and PI3K/Akt signaling, as reflected by the increase in phosphorylation of Akt and mammalian target of rapamycin. Intracisternal infusion of tempol or microinjection into the bilateral RVLM of adenovirus encoding superoxide dismutase significantly antagonized the PTEN inactivation and blunted the enhanced PI3K/Akt signaling in SHR. Gene transfer of PTEN to RVLM in SHR also abrogated the enhanced Akt activation and promoted antihypertension. Silencing PTEN expression in RVLM with small-interfering RNA, on the other hand, augmented PI3K/Akt signaling and promoted long-term pressor response in normotensive WKY rats. Innovation: The present study demonstrated for the first time that the redox-sensitive check-and-balance process between PTEN and PI3K/Akt signaling is engaged in the pathogenesis of hypertension. Conclusion: We conclude that an aberrant interplay between the redox-sensitive PTEN and PI3k/Akt signaling in RVLM underpins neural mechanism of hypertension. Antioxid. Redox Signal. 18, 36–50. PMID:22746319

  1. 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

  2. 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.

  3. Expression of Calcium Channel Subunit Variants in Small Mesenteric Arteries of WKY and SHR

    PubMed Central

    Fromme, Samantha

    2015-01-01

    BACKGROUND Enhanced function of dihydropyridine-sensitive Ca2+ channels (CaV) in hypertensive arterial myocytes (HAM) is well accepted. Increased protein expression of pore forming α1-subunits contributes to this effect, but cannot explain all of the differences in CaV properties in HAM. We hypothesized that differences in expression of CaV subunits and/or their splice variants also contribute. METHODS RNA, protein, and myocytes were isolated from small mesenteric arteries (SMA) of 20-week-old male WKY and SHR and analyzed by polymerase chain reaction (PCR), sequencing, immunoblotting, and patch clamp methods. RESULTS Cav1.2 α1, β2c, and α2δ1d were the dominant subunits expressed in both WKY and SHR with a smaller amount of β3a. Real-time PCR indicated that the mRNA abundance of β3a and α2δ1 but not total Cav1.2 α1 or β2c were significantly larger in SHR. Analysis of alternative splicing of Cav1.2 α1 showed no differences in abundance of mutually exclusive exons1b, 8, 21 and 32 or alternative exons33 and 45. However, inclusion of exon9* was higher and a 73 nucleotide (nt) deletion in exon15 (exon15Δ73) was lower in SHR. Immunoblot analysis showed higher protein levels of Cav1.2 α1 (1.61±0.05), β3 (1.80±0.32), and α2δ1 (1.80±0.24) but not β2 in SHR. CONCLUSIONS The lower abundance of exon15Δ73 transcripts in SHR results in a larger fraction of total Cav1.2 mRNA coding for full-length CaV protein, and the higher abundance of exon9* transcripts and CaVβ3a protein likely contribute to differences in gating and kinetics of CaV currents in SHR. Functional studies of Ca2+ currents in native SMA myocytes and HEK cells transiently transfected with CaV subunits support these conclusions. PMID:25820242

  4. 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.

  5. Avoidance perseveration during extinction training in Wistar-Kyoto rats: an interaction of innate vulnerability and stressor intensity.

    PubMed

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

    2011-08-01

    Given that avoidance is a core feature of anxiety disorders, Wistar-Kyoto (WKY) rats may be a good model of anxiety vulnerability for their hypersensitivity to stress and trait behavioral inhibition. Here, we examined the influence of strain and shock intensity on avoidance acquisition and extinction. Accordingly, we trained WKY and Sprague-Dawley (SD) rats in lever-press avoidance using either 1.0-mA or 2.0-mA foot-shock. After extinction, neuronal activation was visualized by c-Fos for overall activity and parvalbumin immunoreactivity for gamma-aminobutyric acid (GABA) neuron in brain areas linked to anxiety (medial prefrontal cortex and amygdala). Consistent with earlier work, WKY rats acquired lever-press avoidance faster and to a greater extent than SD rats. However, the intensity of foot shock did not differentially affect acquisition. Although there were no differences during extinction in SD rats, avoidance responses of WKY rats trained with the higher foot shock perseverated during extinction compared to those WKY rats trained with lower foot shock intensity or SD rats. WKY rats trained with 2.0-mA shock exhibited less GABAergic activation in the basolateral amygdala after extinction. These findings suggest that inhibitory modulation in amygdala is important to ensure successful extinction learning. Deficits in avoidance extinction secondary to lower GABAergic activation in baslolateral amygdala may contribute to anxiety vulnerability in this animal model of inhibited temperament.

  6. Improvement of Acetylcholine-Induced Vasodilation by Acute Exercise in Ovariectomized Hypertensive Rats.

    PubMed

    Cheng, Tsung-Lin; Lin, Yi-Yuan; Su, Chia-Ting; Hu, Chun-Che; Yang, Ai-Lun

    2016-06-30

    Postmenopause is associated with the development of cardiovascular disease, such as hypertension. However, limited information is available regarding effects of exercise on cardiovascular responses and its underlying mechanisms in the simultaneous postmenopausal and hypertensive status. We aimed to investigate whether acute exercise could enhance vasodilation mediated by acetylcholine (ACh) and sodium nitroprusside (SNP) in ovariectomized hypertensive rats. The fifteen-week-old female spontaneously hypertensive rats (SHR) were bilaterally ovariectomized, at the age of twenty-four weeks, and randomly divided into sedentary (SHR-O) and acute exercise (SHR-OE) groups. Age-matched WKY rats were used as the normotensive control group. The SHR-OE group ran on a motor-driven treadmill at a speed of 24 m/min for one hour in a moderate-intensity program. Following a single bout of exercise, rat aortas were isolated for the evaluation of the endothelium-dependent (ACh-induced) and endothelium-independent (SNP-induced) vasodilation by the organ bath system. Also, the serum levels of oxidative stress and antioxidant activities, including malondialdehyde (MDA), superoxide dismutase (SOD), and catalase, were measured after acute exercise among the three groups. We found that acute exercise significantly enhanced the ACh-induced vasodilation, but not the SNP-induced vasodilation, in ovariectomized hypertensive rats. This increased vasodilation was eliminated after the inhibition of nitric oxide synthase (NOS). Also, the activities of SOD and catalase were significantly increased after acute exercise, whereas the level of MDA was comparable among the three groups. These results indicated that acute exercise improved the endothelium-dependent vasodilating response to ACh through the NOS-related pathway in ovariectomized hypertensive rats, which might be associated with increased serum antioxidant activities.

  7. The effects of captopril on cardiac regression, blood pressure and bradykinin components in diabetic Wistar Kyoto rats.

    PubMed

    Sharma, J N; Kesavarao, U

    2011-01-01

    The present study examined the left ventricular wall thickness (LVWT), total urinary kallikrein, total plasma kininogen and mean arterial blood pressure (MABP) in diabetic and non-diabetic Wistar Kyoto (WKY) rats. The MABP was significantly raised (P<0.01) in diabetic WKY rats compared to the respective controls. The LVWT was also significantly (P<0.01) increased in diabetic WKY rats than that of control WKY rats. The mean total urinary kallikrein level and the mean total plasma kininogen level were higher (P<0.01) in diabetic WKY rats, when these rats were treated with captopril (40 mg/kg and 80 mg/kg) against the mean value obtained from control WKY rats. In conclusion, this investigation suggests that diabetes induced in these rats can cause hypertension, increased LVWT and changes in the BK-forming components. Captopril treatment caused reduction in MABP, regression of LVWT and alterations in bradykinin (BK)-forming components. The possible significance of these observations is discussed.

  8. Interaction of nimesulide, a cyclooxygenase-2 inhibitor, with cisplatin in normotensive and spontaneously hypertensive rats.

    PubMed

    Al Suleimani, Yousuf M; Abdelrahman, Aly M; AlMahruqi, Ahmed S; Alhseini, Ishaq S; Tageldin, Mohamed H; Mansour, Mohamed E; Ali, Badreldin H

    2010-01-01

    We investigated the effect of administration of nimesulide, a selective cyclooxygenase-2 (COX-2) inhibitor, on cisplatin (CP)-induced nephrotoxicity in rats. WKY rats and SHRs were divided into four groups, each. The first and second groups received saline and oral nimesulide (20mg/kg/day for 6 days), respectively, whereas the third and fourth groups received a single intraperitoneal (i.p.) injection of CP (5mg/kg) and CP (5mg/kg) and nimesulide (20mg/kg/day for 5 days), respectively. At the end of the experiment, rats were anesthetized and blood pressure and renal blood flow (RBF) were monitored, followed by intravenous (i.v.) injection of norepinephrine (NE). Nephrotoxicity was evaluated histopathologically and biochemically. CP caused a reduction in baseline RBF in both WKY and SHRs. It increased the concentrations of urea and creatinine and kidney relative weight, and decreased body weight in both WKY and SHRs. Histopathologically, CP caused remarkable renal damage in both WKY rats and SHRs. Treatment with nimesulide alone did not produce any significant change in any of the above measurements. However, nimesulide aggravated CP-induced renal tissue damage in SHRs, but not in WKY rats. The results show that administration nimesulide augmented the histopathological indices of nephrotoxicity in SHRs, but not in WKY rats.

  9. Reduced effect of caffeine on twitch contraction of oesophageal striated muscle from stroke-prone spontaneously hypertensive rats.

    PubMed

    Sekiguchi, Fumiko; Kawata, Kyoko; Shimamura, Keiichi; Sunano, Satoru

    2003-04-01

    1. There are known differences in the sensitivity to caffeine between skeletal muscle (soleus) of normotensive Wistar-Kyoto (WKY) rats and spontaneously hypertensive rats (SHR). The present study was performed in order to examine differences in the effects of caffeine on twitch contraction between visceral striated muscle using the outer layer of the oesophagus from WKY rats and stroke-prone SHR (SHRSP). 2. Caffeine, at concentrations ranging from 0.3 to 10 mmol/L, exhibited potentiating effects on twitch contraction in preparations from both WKY rats and SHRSP. The potentiating effect of caffeine was markedly less prominent in preparations from SHRSP compared with preparations from WKY rats. 3. The rate of contraction and relaxation, the time to peak tension and 80% relaxation time were not significantly altered by caffeine at concentrations lower than 3 mmol/L in preparations from either strain. 4. With 10 mmol/L caffeine, the rate of relaxation was markedly reduced and the 80% relaxation time was prolonged, with no significant changes in the rate of contraction, in preparations from WKY rats. These changes were significantly smaller in preparations from SHRSP. 5. The duration of the action potential was greater in preparations from SHRSP than in preparations from WKY rats, although the membrane potential and the amplitude of the action potential were not significantly different between preparations from WKY rats and SHRSP. 6. Caffeine, at 10 mmol/L, prolonged the duration of the action potential in preparations from both strains. The effect of caffeine was not different between preparations from WKY rats and SHRSP. 7. The results of the present study suggest that caffeine augments release of Ca2+ from the sarcoplasmic reticulum (SR) at low concentrations and attenuates Ca2+ re-uptake at 10 mmol/L. Decreased reactivity of SR to caffeine may be a cause of the lesser potentiation of twitch contraction by caffeine in preparations from SHRSP.

  10. 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...

  11. 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

  12. Associations Between Physical Fitness Indices and Working Memory in Breast Cancer Survivors and Age-Matched Controls

    PubMed Central

    Mackenzie, Michael J.; Zuniga, Krystle E.; Raine, Lauren B.; Awick, Elizabeth A.; Hillman, Charles H.; Kramer, Arthur F.

    2016-01-01

    Abstract Background: This study examined the effects of cardiorespiratory fitness, heart rate recovery, and physical activity on working memory in breast cancer survivors and age-matched controls. Method: Using a case-control design, 32 women who had received a breast cancer diagnosis and completed primary treatment within the past 36-months (11 radiation only; 21 chemotherapy) and 30 age-matched women with no previous cancer diagnosis completed a n-back continuous performance task commonly used as an assessment of working memory. In addition, cardiorespiratory fitness and heart rate recovery were measured during a submaximal graded exercise test and physical activity was measured using 7-days of accelerometer monitoring. Results: Breast cancer survivors who had received chemotherapy had poorer heart rate recovery (p = .010) and engaged in less physical activity than women who had received radiation only (p = .004) or non-cancer controls (p = .029). Cancer treatment (radiation; chemotherapy) predicted differences in reaction times on the 1-back working memory task (p = .029). However, more rapid heart rate recovery predicted shorter reaction times on the 1-back task in the age-matched control group (p = .002). All participants with greater cardiorespiratory fitness displayed greater accuracy independent of disease status on the 1-back task (p = .017). No significant group differences in reaction times were observed for 2-back target trials between breast cancer survivors and controls. However, greater total physical activity predicted shorter reaction times in breast cancer survivors (radiation, chemotherapy) on the 2-back task (p = .014). In addition, all participants who exhibited more rapid heart rate recovery demonstrated better greater accuracy regardless of disease status (p = .013). Conclusion: These findings support differences in physical activty participation, heart rate recovery, and 1- and 2-back working memory reaction

  13. EXACERBATED MECHANICAL ALLODYNIA IN RATS WITH DEPRESSION-LIKE BEHAVIOR

    PubMed Central

    Zeng, Qing; Wang, Shuxing; Lim, Grewo; Yang, Liling; Mao, Ji; Sung, Backil; Chang, Yang; Lim, Jeong-Ae; Guo, Gongshe; Mao, Jianren

    2008-01-01

    Although a clinical connection between pain and depression has long been recognized, how these two conditions interact remains unclear. Here we report that both mechanical allodynia and depression-like behavior were significantly exacerbated after peripheral nerve injury in Wistar-Kyoto (WKY) rats, a genetic variation of Wistar rats with demonstrable depression-like behavior. Administration of melatonin into the anterior cingular cortex contralateral to peripheral nerve injury prevented the exacerbation of mechanical allodynia with a concurrent improvement of depression-like behavior in WKY rats. Moreover, there was a lower plasma melatonin concentration and a lower melatonin receptor expression in the anterior cingular cortex in WKY rats than in Wistar rats. These results suggest that there exists a reciprocal relationship between mechanical allodynia and depression-like behavior and the melotoninergic system in the anterior cingular cortex might play an important role in the interaction between pain and depression. PMID:18289511

  14. Are the prevalence and treatment of asthma similar in elite athletes and the aged-matched non-athlete population?

    PubMed

    Locke, S; Marks, G

    2007-12-01

    The objective of this study was to determine the prevalence of asthma and use of asthma medications in elite athletes compared with an age-matched non-athlete population. Data were collected from the respiratory component of annual medical screening of 424 elite athletes from the Queensland Academy of Sport. Measures included the prevalence of current asthma and ever doctor-diagnosed asthma, and the prevalence of use of treatment for asthma including beta-agonists and inhaled corticosteroid medication. The prevalence of current asthma in athletes aged 18-29 years was 14% (95% CI, 9-19%), which did not differ significantly from the prevalence in the non-athlete control population (11%; 95% CI, 9-12%, P=0.3). Of athletes with current asthma, 27% were not taking any medications for asthma, and 25% were treated with short-acting beta-agonist medications alone and were not taking inhaled corticosteroids. These data indicate that the overall cumulative and period prevalence of asthma in Queensland athletes is similar to that in the general age-matched population. Athletes use beta-agonists with a frequency similar to the general population.

  15. Superoxide dismutase reduces the impairment of endothelium-dependent relaxation in the spontaneously hypertensive rat aorta.

    PubMed

    Sekiguchi, Fumiko; Yanamoto, Aiko; Sunano, Satoru

    2004-04-01

    The involvement of the superoxide anion in endothelium-dependent relaxation (EDR) was examined in noradrenaline-contracted aortic smooth muscle preparations isolated from normotensive Wistar Kyoto rats (WKY) and stroke-prone spontaneously hypertensive rats (SHRSP). Acetylcholine (ACh, 10(-9)-10(-5) M) induced EDR in both WKY and SHRSP preparations in a concentration-dependent manner, but with a significantly smaller amplitude in those from SHRSP than in those from WKY. The ACh-induced EDR was inhibited by N(omega)-nitro-L-arginine (L-NOARG), in a concentration-dependent manner, both in WKY and SHRSP. The EDR produced in WKY in the presence of 3 x 10(-6) M L-NOARG was similar in magnitude to that produced in SHRSP in the absence of L-NOARG. Superoxide dismutase (SOD, 300 units/ml) increased the amplitude of EDR in SHRSP but not in WKY, with no alteration of the threshold or of the maximal amplitude. The maximal amplitude of EDR produced in SHRSP in the presence of SOD was still smaller than that in WKY. In WKY, a possible involvement of superoxide in the EDR was examined in aortae whose EDR was partially inhibited by treatment with a subthreshold concentration (3 x 10 (-6) M) of L-NOARG. In the L-NOARG-conditioned aorta, the reduced EDR was partially but significantly recovered by SOD. These results suggest that the impaired EDR in aortae of SHRSP may be causally related to a higher production of superoxide. The L-NOARG-induced inhibition of EDR in WKY may be produced, in part, by the reduction of effective NO due to its destruction by superoxide.

  16. Expression of brain-derived neurotrophic factor immunoreactivity and mRNA in the hippocampal CA1 and cortical areas after chronic ischemia in rats.

    PubMed

    Lee, Tsong-Hai; Yang, Jen-Tsung; Kato, Hiroyuki; Wu, June Hsieh; Chen, Sien-Tsong

    2004-06-01

    We studied the expression of brain-derived neurotrophic factor (BDNF) immunoreactivity and mRNA in the ischemia-vulnerable cerebral hippocampal CA1 and cortical areas after permanent occlusion of bilateral internal carotid arteries. Four groups of rats were studied, including 1) young normotensive Wistar-Kyoto (WKY) rats, 2) aged normotensive WKY rats, 3) young spontaneous hypertensive rats (SHR), and 4) aged SHR. Each group contained rats from sham operation and 1 week, 4 weeks, and 8 weeks after cerebral ischemia (n = 3-5 at each time point). Hematoxylin and eosin staining and in situ apoptosis detection showed no neuronal damage from 1 week to 8 weeks in all the ischemic rats. Immunohistochemistry and Western blot showed that BDNF immunoreactivity increased only at 1 week in the CA1 area of young WKY rats (P < .001) and SHR (P = .002) and decreased only at 8 weeks in the cortical area of aged WKY rats (P = .02). In situ hybridization and TaqMan real-time RT-PCR showed that BDNF mRNA decreased consistently from 1 week to 8 weeks in both CA1 and cortical areas in young SHR (P < .05 and P < .01, respectively) and in aged WKY rats (P < .01 and P < .05, respectively) but was not changed in young WKY rats or aged SHR (P > .05) compared with the sham-operated rats. Our study demonstrates an expression disparity of BDNF immunoreactivity and mRNA in the hippocampal CA1 and cortical areas, especially in the young SHR and aged WKY rats after mild cerebral ischemia. Our study suggests that, under permanent occlusion of bilateral internal carotid arteries, aging and the level of blood pressure may have influence on the expression of BDNF.

  17. 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

  18. Puerarin Attenuates Cerebral Damage by Improving Cerebral Microcirculation in Spontaneously Hypertensive Rats

    PubMed Central

    Wu, Xu-Dong; Wang, Chen; Zhang, Zhen-Ying; Fu, Yan; Liu, Feng-Ying; Liu, Xiu-Hua

    2014-01-01

    Puerariae Lobatae Radix (Gegen in Chinese) is the dried root of Pueraria lobata, a semiwoody, perennial, and leguminous vine native to China. Puerarin is one of the effective components of isoflavones isolated from the root of Pueraria lobata. Previous studies showed that extracts derived from the root of Pueraria lobata possessed antihypertensive effect. Our study is to investigate whether puerarin contributes to prevention of stroke by improving cerebral microcirculation in rats. Materials and Methods. Video microscopy and laser Doppler perfusion imaging on the pia mater were used to measure the diameter of microvessel and blood perfusion in 12-week old spontaneously hypertensive rats (SHRs) and age-matched normotensive WKY rats. Histological alterations were observed by hematoxylin and eosin staining, and microvessel density in cerebral tissue was measured by immunohistochemical analysis with anti-Factor VIII antibody. Cell proliferation was detected by [3H]-TdR incorporation, and activities of p42/44 mitogen activated protein kinases (p42/44 MAPKs) were detected by western blot analysis in cultured cerebral microvascular endothelial cells (MECs). Results. Intravenous injection of puerarin relaxed arterioles and increased the blood flow perfusion in the pia mater in SHRs. Puerarin treatment for 14 days reduced the blood pressure to a normal level in SHRs (P < 0.05) and increased the arteriole diameter in the pia mater significantly as compared with vehicle treatment. Arteriole remodeling, edema, and ischemia in cerebral tissue were attenuated in puerarin-treated SHRs. Microvessel density in cerebral tissue was greater with puerarin than with vehicle treatment. Puerarin-treated MECs showed greater proliferation and p42/44 MAPKs activities than vehicle treatment. Conclusions. Puerarin possesses effects of antihypertension and stroke prevention by improved microcirculation in SHRs, which results from the increase in cerebral blood perfusion both by arteriole

  19. Puerarin attenuates cerebral damage by improving cerebral microcirculation in spontaneously hypertensive rats.

    PubMed

    Wu, Xu-Dong; Wang, Chen; Zhang, Zhen-Ying; Fu, Yan; Liu, Feng-Ying; Liu, Xiu-Hua

    2014-01-01

    Puerariae Lobatae Radix (Gegen in Chinese) is the dried root of Pueraria lobata, a semiwoody, perennial, and leguminous vine native to China. Puerarin is one of the effective components of isoflavones isolated from the root of Pueraria lobata. Previous studies showed that extracts derived from the root of Pueraria lobata possessed antihypertensive effect. Our study is to investigate whether puerarin contributes to prevention of stroke by improving cerebral microcirculation in rats. Materials and Methods. Video microscopy and laser Doppler perfusion imaging on the pia mater were used to measure the diameter of microvessel and blood perfusion in 12-week old spontaneously hypertensive rats (SHRs) and age-matched normotensive WKY rats. Histological alterations were observed by hematoxylin and eosin staining, and microvessel density in cerebral tissue was measured by immunohistochemical analysis with anti-Factor VIII antibody. Cell proliferation was detected by [(3)H]-TdR incorporation, and activities of p42/44 mitogen activated protein kinases (p42/44 MAPKs) were detected by western blot analysis in cultured cerebral microvascular endothelial cells (MECs). Results. Intravenous injection of puerarin relaxed arterioles and increased the blood flow perfusion in the pia mater in SHRs. Puerarin treatment for 14 days reduced the blood pressure to a normal level in SHRs (P < 0.05) and increased the arteriole diameter in the pia mater significantly as compared with vehicle treatment. Arteriole remodeling, edema, and ischemia in cerebral tissue were attenuated in puerarin-treated SHRs. Microvessel density in cerebral tissue was greater with puerarin than with vehicle treatment. Puerarin-treated MECs showed greater proliferation and p42/44 MAPKs activities than vehicle treatment. Conclusions. Puerarin possesses effects of antihypertension and stroke prevention by improved microcirculation in SHRs, which results from the increase in cerebral blood perfusion both by arteriole

  20. Energy Deregulation Precedes Alteration in Heart Energy Balance in Young Spontaneously Hypertensive Rats: A Non Invasive In Vivo 31P-MR Spectroscopy Follow-Up Study

    PubMed Central

    Deschodt-Arsac, Veronique; Arsac, Laurent; Magat, Julie; Naulin, Jerome; Quesson, Bruno; Dos Santos, Pierre

    2016-01-01

    Introduction Gradual alterations in cardiac energy balance, as assessed by the myocardial PCr/ATP-ratio, are frequently associated with the development of cardiac disease. Despite great interest for the follow-up of myocardial PCr and ATP content, cardiac MR-spectroscopy in rat models in vivo is challenged by sensitivity issues and cross-contamination from other organs. Methods Here we combined MR-Imaging and MR-Spectroscopy (Bruker BioSpec 9.4T) to follow-up for the first time in vivo the cardiac energy balance in the SHR, a genetic rat model of cardiac hypertrophy known to develop early disturbances in cytosolic calcium dynamics. Results We obtained consistent 31P-spectra with high signal/noise ratio from the left ventricle in vivo by using a double-tuned (31P/1H) surface coil. Reasonable acquisition time (<3.2min) allowed assessing the PCr/ATP-ratio comparatively in SHR and age-matched control rats (WKY): i) weekly from 12 to 21 weeks of age; ii) in response to a bolus injection of the ß-adrenoreceptor agonist isoproterenol at age 21 weeks. Discussion Along weeks, the cardiac PCr/ATP-ratio was highly reproducible, steady and similar (2.35±0.06) in SHR and WKY, in spite of detectable ventricular hypertrophy in SHR. At the age 21 weeks, PCr/ATP dropped more markedly (-17.1%±0.8% vs. -3,5%±1.4%, P<0.001) after isoproterenol injection in SHR and recovered slowly thereafter (time constant 21.2min vs. 6.6min, P<0.05) despite similar profiles of tachycardia among rats. Conclusion The exacerbated PCr/ATP drop under ß-adrenergic stimulation indicates a defect in cardiac energy regulation possibly due to calcium-mediated abnormalities in the SHR heart. Of note, defects in energy regulation were present before detectable abnormalities in cardiac energy balance at rest. PMID:27622548

  1. Dysfunctional Inhibitory Mechanisms in Locus Coeruleus Neurons of the Wistar Kyoto Rat

    PubMed Central

    Bruzos-Cidón, C; Llamosas, N; Ugedo, L

    2015-01-01

    Background: The noradrenergic nucleus locus coeruleus (LC) has functional relevance in several psychopathologies such as stress, anxiety, and depression. In addition to glutamatergic and GABAergic synaptic inputs, the activation of somatodendritic α2-adrenoceptors is the main responsible for LC activity regulation. The Wistar Kyoto (WKY) rat exhibits depressive- and anxiety-like behaviors and hyperresponse to stressors. Thus, the goal of the present study was to investigate in vitro the sensitivity of α2-adrenoceptors, as well as the glutamatergic and GABAergic synaptic activity on LC neurons of the WKY strain. Methods: For that purpose patch-clamp whole-cell recordings were done in LC slices. Results: The α2-adrenoceptors of LC neurons from WKY rats were less sensitive to the effect induced by the agonist UK 14 304 as compared to that recorded in the Wistar (Wis) control strain. In addition, the GABAergic input to LC neurons of WKY rats was significantly modified compared to that in Wis rats, since the amplitude of spontaneous GABAergic postsynaptic currents was reduced and the half-width increased. On the contrary, no significant alterations were detected regarding glutamatergic input to LC neurons between rat strains. Conclusions: These results point out that in WKY rats the inhibitory control exerted by α2-adrenoceptors and GABAergic input onto LC neurons is dysregulated. Overall, this study supports in this animal model the hypothesis that claims an imbalance between the glutamatergic-GABAergic systems as a key factor in the pathophysiology of depression. PMID:25586927

  2. Role of the genetic background of rats in infection by HTLV-I and HTLV-II and in the development of associated diseases.

    PubMed

    Kazanji, M; Ibrahim, F; Fiette, L; Bomford, R; De Thé, G

    1997-09-26

    Three aspects of the rat model of HTLV-I/II infection were investigated. (i) The efficacy of HTLV-I-transformed rat cell lines in infecting different strains of rats: WKY and Lewis HTLV-I-transformed cell lines were injected into adult WKY, Lewis and Brown Norway rats, representing syngeneic and allogeneic combinations. The HTLV-I provirus was not detected in peripheral-blood mononuclear cells (PBMC) from these rats 18 weeks after inoculation, showing that HTLV-I-transformed rat cells are not suitable for virus challenge in vaccination experiments. Rats inoculated with Lewis HTLV-I-transformed cells produced an antibody response to HTLV-I, which was higher in allogeneic (WKY and Brown Norway) than in syngeneic rats. (ii) The susceptibility of rats to HTLV-II infection: After human HTLV-II-producing cells (MO) were injected into adult WKY rats, the HTLV-II provirus was detected in PBMC 12 weeks later. Sequencing of a portion of this provirus confirmed its identity with the HTLV-II from MO cells. (iii) The role of MHC haplotype in susceptibility to neurological disease in rats inoculated as newborns with HTLV-I: The hypothesis that the RT-Ik haplotype confers susceptibility was tested by inoculating newborn OKA (RT-Ik), WKY (RT-Il), Lewis (RT-Il) and Fischer 344 (RT-I lvl) rats with human HTLV-I-producing cells (MT-2). Eighteen months later, only the WKY rats showed histological abnormality of the spinal cord, without clinical paralysis. Fischer 344 rats developed cutaneous tumors and OKA rats mammary tumors. The HTLV-I provirus was not detected in these tumors.

  3. Nociception and Conditioned Fear in Rats: Strains Matter

    PubMed Central

    Schaap, Manon W. H.; van Oostrom, Hugo; Doornenbal, Arie; van 't Klooster, José; Baars, Annemarie M.; Arndt, Saskia S.; Hellebrekers, Ludo J.

    2013-01-01

    When using rats in pain research, strain-related differences in outcomes of tests for pain and nociception are acknowledged. However, very little is known about the specific characteristics of these strain differences. In this study four phylogenetically distant inbred rat strains, i.e. Wistar Kyoto (WKY), Fawn Hooded (FH), Brown Norway (BN) and Lewis (LE), were investigated in different tests related to pain and nociception. During Pavlovian fear conditioning, the LE and WKY showed a significantly longer duration of freezing behaviour than the FH and BN. Additionally, differences in c-Fos expression in subregions of the prefrontal cortex and amygdala between rat strains during retrieval and expression of conditioned fear were found. For example, the BN did not show recruitment of the basolateral amygdala, whereas the WKY, FH and LE did. During the hot plate test, the WKY and LE showed a lower thermal threshold compared to the BN and FH. In a follow-up experiment, the two most contrasting strains regarding behaviour during the hot plate test and Pavlovian fear conditioning (i.e. FH and WKY) were selected and the hot plate test, Von Frey test and somatosensory-evoked potential (SEP) were investigated. During the Von Frey test, the WKY showed a lower mechanical threshold compared to the FH. When measuring the SEP, the FH appeared to be less reactive to increasing stimulus intensities when considering both peak amplitudes and latencies. Altogether, the combined results indicate various differences between rat strains in Pavlovian fear conditioning, nociception related behaviours and nociceptive processing. These findings demonstrate the necessity of using multiple rat strains when using tests including noxious stimuli and suggest that the choice of rat strains should be considered. When selecting a strain for a particular study it should be considered how this strain behaves during the tests used in that study. PMID:24376690

  4. /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.

  5. 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...

  6. 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...

  7. 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...

  8. 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...

  9. Adrenergic and purinergic components in bisected vas deferens from spontaneously hypertensive rats

    PubMed Central

    Guitart, Mònica; Giraldo, Jesús; Goñalons, Eduard; Vila, Elisabet; Badia, Albert

    1999-01-01

    Purinergic and adrenergic components of the contractile response to electrical field stimulation (EFS) have been investigated in epididymal and prostatic portions of Wystar Kyoto (WKY) and spontaneously hypertensive rat (SHR) vas deferens. In both halves of SHR and WKY vas deferens, EFS (40 V, 0.5 ms for 30 s, 0.5–32 Hz) evoked frequency-related contractions. The neurogenic responses were biphasic, consisting of a rapid non-adrenergic response, dominant in the prostatic portion, followed by a slow tonic adrenergic component, dominant in the epididymal half. Phasic and tonic components of the frequency-response curves evoked by EFS were significantly higher in the epididymal but not in the prostatic portion of vas deferens from SHR compared to WKY rats. The α1-adrenoceptor antagonist prazosin (0.1 μM) was more effective against both components of the contractile response in the epididymal end of SHR than in WKY rats. Inhibition by α,β-methylene adenosine 5′-triphosphate (α,β-meATP 3 and 30 μM) was higher in both components of the contractile responses in WKY preparations than in SHR. Combined α1-adrenoceptor and P2x-purinoceptor antagonism virtually abolished the EFS-evoked contractile response in both strains. The degree of inhibition by prazosin (0.1 μM) after P2x-purinoceptor blockade was higher in SHR than in WKY rats. These results demonstrate a modification in the purinergic and noradrenergic contribution to neurogenic responses in SHR and WKY animals besides a co-participation of ATP and noradrenaline in both contractile components of the response to EFS. PMID:10556921

  10. Preserved Learning during the Symbol–Digit Substitution Test in Patients with Schizophrenia, Age-Matched Controls, and Elderly

    PubMed Central

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

    2015-01-01

    Objective: Speed of processing, one of the main cognitive deficits in schizophrenia is most frequently measured with a digit–symbol-coding test. Performance on this test is additionally affected by writing speed and the rate at which symbol–digit relationships are learned, two factors that may be impaired in schizophrenia. This study aims to investigate the effects of sensorimotor speed, short-term learning, and long-term learning on task performance in schizophrenia. In addition, the study aims to explore differences in learning effects between patients with schizophrenia and elderly individuals. Methods: Patients with schizophrenia (N = 30) were compared with age-matched healthy controls (N = 30) and healthy elderly volunteers (N = 30) during the Symbol–Digit Substitution Test (SDST). The task was administered on a digitizing tablet, allowing precise measurements of the time taken to write each digit (writing time) and the time to decode symbols into their corresponding digits (matching time). The SDST was administered on three separate days (day 1, day 2, day 7). Symbol–digit repetitions during the task represented short-term learning and repeating the task on different days represented long-term learning. Results: The repetition of the same symbol–digit combinations within one test and the repetition of the test over days resulted in significant decreases in matching time. Interestingly, these short-term and long-term learning effects were about equal among the three groups. Individual participants showed a large variation in the rate of short-term learning. In general, patients with schizophrenia had the longest matching time whereas the elderly had the longest writing time. Writing time remained the same over repeated testing. Conclusion: The rate of learning and sensorimotor speed was found to have a substantial influence on the SDST score. However, a large individual variation in learning rate should be taken into account in the

  11. 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

  12. 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.

  13. Long-term effects of chronic oral Ritalin administration on cognitive and neural development in adolescent wistar kyoto rats.

    PubMed

    Pardey, Margery C; Kumar, Natasha N; Goodchild, Ann K; Clemens, Kelly J; Homewood, Judi; Cornish, Jennifer L

    2012-09-12

    The diagnosis of Attention Deficit Hyperactivity Disorder (ADHD) often results in chronic treatment with psychostimulants such as methylphenidate (MPH, Ritalin®). With increases in misdiagnosis of ADHD, children may be inappropriately exposed to chronic psychostimulant treatment during development. The aim of this study was to assess the effect of chronic Ritalin treatment on cognitive and neural development in misdiagnosed "normal" (Wistar Kyoto, WKY) rats and in Spontaneously Hypertensive Rats (SHR), a model of ADHD. Adolescent male animals were treated for four weeks with oral Ritalin® (2 × 2 mg/kg/day) or distilled water (dH2O). The effect of chronic treatment on delayed reinforcement tasks (DRT) and tyrosine hydroxylase immunoreactivity (TH-ir) in the prefrontal cortex was assessed. Two weeks following chronic treatment, WKY rats previously exposed to MPH chose the delayed reinforcer significantly less than the dH2O treated controls in both the DRT and extinction task. MPH treatment did not significantly alter cognitive performance in the SHR. TH-ir in the infralimbic cortex was significantly altered by age and behavioural experience in WKY and SHR, however this effect was not evident in WKY rats treated with MPH. These results suggest that chronic treatment with MPH throughout adolescence in "normal" WKY rats increased impulsive choice and altered catecholamine development when compared to vehicle controls.

  14. Long-Term Effects of Chronic Oral Ritalin Administration on Cognitive and Neural Development in Adolescent Wistar Kyoto Rats

    PubMed Central

    Pardey, Margery C.; Kumar, Natasha N.; Goodchild, Ann K.; Clemens, Kelly J.; Homewood, Judi; Cornish, Jennifer L.

    2012-01-01

    The diagnosis of Attention Deficit Hyperactivity Disorder (ADHD) often results in chronic treatment with psychostimulants such as methylphenidate (MPH, Ritalin®). With increases in misdiagnosis of ADHD, children may be inappropriately exposed to chronic psychostimulant treatment during development. The aim of this study was to assess the effect of chronic Ritalin treatment on cognitive and neural development in misdiagnosed “normal” (Wistar Kyoto, WKY) rats and in Spontaneously Hypertensive Rats (SHR), a model of ADHD. Adolescent male animals were treated for four weeks with oral Ritalin® (2 × 2 mg/kg/day) or distilled water (dH2O). The effect of chronic treatment on delayed reinforcement tasks (DRT) and tyrosine hydroxylase immunoreactivity (TH-ir) in the prefrontal cortex was assessed. Two weeks following chronic treatment, WKY rats previously exposed to MPH chose the delayed reinforcer significantly less than the dH2O treated controls in both the DRT and extinction task. MPH treatment did not significantly alter cognitive performance in the SHR. TH-ir in the infralimbic cortex was significantly altered by age and behavioural experience in WKY and SHR, however this effect was not evident in WKY rats treated with MPH. These results suggest that chronic treatment with MPH throughout adolescence in “normal” WKY rats increased impulsive choice and altered catecholamine development when compared to vehicle controls. PMID:24961199

  15. 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.

  16. 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

  17. 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

  18. Metabolism and hepatorenal toxicity due to repeated exposure to styrene in spontaneously hypertensive rats (SHR)

    SciTech Connect

    Decarie, S.; Chakrabarti, S. )

    1989-01-01

    Groups of adult make rats (5 rats per group), either normotensive (WKY) or spontaneously hypertensive (SHR), were exposed by inhalation to 0, 821, and 3018 ppm styrene, 5h per day for 3 consecutive days. After the exposure, the urines were collected for 24h and the animals were then sacrificed. The various biochemical parameters of henatorenal toxicity due to styrene as well as its urinary metabolites were measured. Hepatotoxicity due to styrene was not further increased at any exposure level due to hypertension. However, repeated exposure of SHR rats to 3018 ppm styrene showed significant increases in the urinary excretion of {gamma}-glutamyl transpeptidase, proteins, and volume of urine, compared to WKY treated rats, whereas no such changes were observed due to repeated exposure to 821 ppm styrene. Studies of in vivo metabolism of styrene at higher exposure level showed significant decrease in the urinary excretion of mandelic, phenylglyoxylic, and hippuric acids in SHR rats compared to WKY-treated rats, suggestion an inhibition of deactivation of styrene reactive intermediate involving the epoxide hydrase pathway due to hypertension. At the same time, a significant increase in the urinary excretion of a potential nephrotoxic metabolite of styrene (e.g., mercapturates or thioethers) was observed in SHR-treated rats when compared to WKY-treated rats. These results demonstrate the spontaneous hpertension has the potential to further increase the nephrotoxicity due to repeated exposure to styrene, and the metabolism of styrene plays an important role in modifying such toxicity in the hypertensive state.

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

    PubMed

    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.

  20. Control of oxidative stress in microcirculation of spontaneously hypertensive rats.

    PubMed

    DeLano, F A; Balete, R; Schmid-Schönbein, G W

    2005-02-01

    One mechanism for organ damage in individuals with arterial hypertension may be due to oxygen free radical production. This study was designed to localize free radicals in a microvascular network of mature spontaneously hypertensive rats (SHRs) and normotensive Wistar-Kyoto (WKY) rats. Because glucocorticoids play a role in pressure elevation of SHRs, we investigated their role in microvascular free radical formation. Oxygen radical production in mesentery was detected by tetranitroblue tetrazolium reduction to formazan aided by digital light-absorption measurements. Formazan deposits were observed in the endothelial cells and lumens of all microvessels and in lymphatic endothelia but were fewer in tissue parenchyma. The formazan distribution in younger (14-16 wk old) WKY rats and SHRs was heterogeneous with low values in capillaries and small arterioles/venules (<30 microm) but enhanced deposits in larger venules. Adrenalectomy served to reduce the formazan density in SHRs to the level of WKY rats, whereas dexamethasone supplementation of the adrenalectomized rats caused elevation in the larger venules of SHRs. In older (40 wk old) SHRs, formazan levels were elevated in all hierarchies of microvessels. After pressure reduction was employed with chronic hydralazine treatment, the formazan deposits were reduced in all locations of the microcirculation in both WKY rats and SHRs. Elevated formazan deposits were also found in lymphatic endothelium. These results suggest that oxygen free radical production is elevated in both high- and low-pressure regions of SHR microcirculation via a process that is controlled by glucocorticoids. Older SHRs have higher formazan levels than younger SHRs in all microvessels. Chronic hydralazine treatment, which serves to reduce arterial blood pressure, attenuates tetranitroblue tetrazolium reduction in WKY rats and SHRs even in venules of the microcirculation, which has no micropressure elevation. Free radical production may be a more

  1. Effects of ovariectomy on indices of insulin resistance, hypertension, and cardiac energy metabolism in middle-aged spontaneously hypertensive rats (SHR).

    PubMed

    Swislocki, A; Burgie, E S; Rodnick, K J

    2002-09-01

    Insulin resistance is a risk factor for coronary heart disease. The protection of young women from coronary events is sharply reduced with menopause. To assess the impact of menopause on glucose tolerance, insulin resistance, body weight gain, heart size, and cardiac energy metabolism, we studied 28-week-old female SHR and Wistar-Kyoto (WKY) rats, who were either ovariectomized (SHR(OVX) and WKY(OVX)) or sham-operated (SHR(SHAM) and WKY(SHAM)). Animals underwent blood-pressure measurement and an oral glucose tolerance test (OGTT). Hearts were weighed and assayed for metabolic enzyme activities. Female SHR were 33 % lighter and hypertensive (+ 36 mmHg), with 33 % larger hearts (when corrected for body weight differences) compared to WKY. Although ovariectomized animals of both strains were heavier overall than their sham-operated counterparts, when heart weights were corrected for body weight, both OVX strains had lighter hearts than both SHAM strains. Glucose and insulin responses during OGTT were similar between the four groups; however, free fatty acid (FFA) responses were approximately 50 % greater in SHR than WKY, although less in SHR(OVX) than SHR(SHAM). WKY(OVX) demonstrated 8 % lower ventricular hexokinase activity than WKY(SHAM), which may reflect reduced cardiac glucose utilization. We also noted 16 % higher citrate synthase activity in WKY hearts. In conclusion, the insulin resistance characteristic of younger SHR is blunted in middle-aged female rats, although FFA responses remain elevated. Ovariectomy did not alter in vivo glucose tolerance in this group; however, sex hormones may be important in maintaining normal heart size and the potential for cardiac glucose metabolism.

  2. 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.

  3. Role of Ca(+)-dependent K-channels in the membrane potential and contractility of aorta from spontaneously hypertensive rats.

    PubMed Central

    Silva, E G; Frediani-Neto, E; Ferreira, A T; Paiva, A C; Paiva, T B

    1994-01-01

    1. Contractile responses to KCl and membrane potentials were determined in aortic rings from spontaneously hypertensive rats (SHR), normotensive Wistar rats (NWR) and Wistar Kyoto rats (WKY) both in the absence and in the presence of the Ca(2+)-dependent K-channel blockers, apamin and tetraethylammonium (TEA). 2. Compared to NWR, aortic rings from WKY and SHR were less reactive and their Ca2+ uptake after stimulation with K+ was decreased. 3. Smooth muscle cell membrane potentials were higher in aortae from SHR and WKY than in NWR aortae, whereas SHR had higher K+ and lower Na+ intracellular activities than WKY and NWR, suggesting overactivity of the Na+/K+ pump in the hypertensive animals. 4. Treatment with apamin caused depolarization of WKY and SHR aortae, and increased their contractile responses to the same level as those of the NWR. Treatment with TEA also caused depolarization of aortae from WKY and SHR, but in the SHR the depolarization induced by TEA was smaller than that produced by apamin and the contractile responses to KCl did not reach the level of those of aortae from NWR. 5. It is concluded that overactivity of Ca(2+)-dependent K-channels in aortae of WKY and SHR contributes to their higher membrane potentials and lower responsiveness to vasoconstrictor stimuli. In SHR, an overactive Na+/K+ pump is also present, and the contribution of apamin-sensitive Ca(2+)-dependent K-channels to the membrane potential and reactivity appears to be more relevant than that of TEA-sensitive channels. PMID:7858844

  4. Enhanced catabolism to acetaldehyde in rostral ventrolateral medullary neurons accounts for the pressor effect of ethanol in spontaneously hypertensive rats.

    PubMed

    El-Mas, Mahmoud M; Abdel-Rahman, Abdel A

    2012-02-01

    We have previously shown that ethanol microinjection into the rostral ventrolateral medulla (RVLM) elicits sympathoexcitation and hypertension in conscious spontaneously hypertensive rats (SHRs) but not in Wistar-Kyoto (WKY) rats. In this study, evidence was sought to implicate the oxidative breakdown of ethanol in this strain-dependent hypertensive action of ethanol. Biochemical experiments revealed significantly higher catalase activity and similar aldehyde dehydrogenase (ALDH) activity in the RVLM of SHRs compared with WKY rats. We also investigated the influence of pharmacological inhibition of catalase (3-aminotriazole) or ALDH (cyanamide) on the cardiovascular effects of intra-RVLM ethanol or its metabolic product acetaldehyde in conscious rats. Compared with vehicle, ethanol (10 μg/rat) elicited a significant increase in blood pressure in SHRs that lasted for the 60-min observation period but had no effect on blood pressure in WKY rats. The first oxidation product, acetaldehyde, played a critical role in ethanol-evoked hypertension because 1) catalase inhibition (3-aminotriazole treatment) virtually abolished the ethanol-evoked pressor response in SHRs, 2) intra-RVLM acetaldehyde (2 μg/rat) reproduced the strain-dependent hypertensive effect of intra-RVLM ethanol, and 3) ALDH inhibition (cyanamide treatment) uncovered a pressor response to intra-RVLM acetaldehyde in WKY rats similar to the response observed in SHRs. These findings support the hypothesis that local production of acetaldehyde, due to enhanced catalase activity, in the RVLM mediates the ethanol-evoked pressor response in SHRs.

  5. Variable reactive hyperemia in normotensive strains of rat.

    PubMed

    Heimlich, J Brett; Pollock, David M

    2014-06-18

    Previous studies from our laboratory report variation in nitric oxide (NO)-dependent arterial pressure within the same strain of normotensive Sprague-Dawley rat dependent upon the commercial vendor supplying the rats. Clinical assessment of endothelial NO activity and endothelial function in general has used postocclusion, flow-mediated dilation (FMD). Therefore, this study was conducted to determine whether the reactive hyperemic response was different between two normotensive strains from two different suppliers, Sprague-Dawley (SD) and Wistar-Kyoto (WKY) rats from Charles River (CR) and Harlan Laboratories (H), respectively. Rats were anesthetized and the femoral artery was occluded for 5 min, with femoral blood flow measured continuously by use of an ultrasonic perivascular flow probe. The average area under the reactive hyperemic response curve (3-min duration) was not different between SD rats from CR (80 ± 23 mL/min∙s; n = 6) and H (94 ± 16 mL/min∙s; n = 6). As previously reported, blood pressures were higher in the SD rats from H versus CR. WKY rats from both suppliers had significantly larger hyperemia; 371 ± 67 versus 281 ± 71 mL/min∙s (n = 5) for the CR and H WKY rats, respectively, but again, were not different between vendors. Blood pressures in WKY rats were similar between vendors. These results suggest that differences in NO bioactivity are not discernable with an adapted FMD protocol in the rat and that normotensive strains of rat can have large differences in reactive hyperemia despite having similar blood pressures.

  6. Variable reactive hyperemia in normotensive strains of rat

    PubMed Central

    Heimlich, J. Brett; Pollock, David M.

    2014-01-01

    Abstract Previous studies from our laboratory report variation in nitric oxide (NO)‐dependent arterial pressure within the same strain of normotensive Sprague–Dawley rat dependent upon the commercial vendor supplying the rats. Clinical assessment of endothelial NO activity and endothelial function in general has used postocclusion, flow‐mediated dilation (FMD). Therefore, this study was conducted to determine whether the reactive hyperemic response was different between two normotensive strains from two different suppliers, Sprague–Dawley (SD) and Wistar–Kyoto (WKY) rats from Charles River (CR) and Harlan Laboratories (H), respectively. Rats were anesthetized and the femoral artery was occluded for 5 min, with femoral blood flow measured continuously by use of an ultrasonic perivascular flow probe. The average area under the reactive hyperemic response curve (3‐min duration) was not different between SD rats from CR (80 ± 23 mL/min∙s; n = 6) and H (94 ± 16 mL/min∙s; n = 6). As previously reported, blood pressures were higher in the SD rats from H versus CR. WKY rats from both suppliers had significantly larger hyperemia; 371 ± 67 versus 281 ± 71 mL/min∙s (n = 5) for the CR and H WKY rats, respectively, but again, were not different between vendors. Blood pressures in WKY rats were similar between vendors. These results suggest that differences in NO bioactivity are not discernable with an adapted FMD protocol in the rat and that normotensive strains of rat can have large differences in reactive hyperemia despite having similar blood pressures. PMID:24944292

  7. 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.

  8. 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.

  9. 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.

  10. 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).

  11. Environmental enrichment prevents anxiety-like behavior induced by progesterone withdrawal in two strains of rats.

    PubMed

    Islas-Preciado, D; López-Rubalcava, C; González-Olvera, J; Gallardo-Tenorio, A; Estrada-Camarena, E

    2016-11-12

    Stress vulnerability could influence the treatment response to anxiety associated with abrupt hormonal suppression. The present study explored the effects of different treatments on experimental anxiety induced by progesterone withdrawal (PW) in a stress-sensitive rat strain, Wistar Kyoto (WKY), in the burying behavior test (BBT). The following experimental series was conducted using independent groups of Wistar (control strain) and WKY ovariectomized rats: Experiment 1: Rats were treated for 5days with oil, a constant dose of progesterone (0.5mg/rat, s.c) or a combination of progesterone (0.5mg/rat, s.c) plus fluoxetine (10 mg/kg, i.p); on day 6, all rats were subjected to BBT. Experiment 2: Rats received corn oil or decreasing doses of progesterone (0.84, 0.67, 0.5, 0.33 and 0.17mg/rat; one dose daily); on day 6, the rats were subjected to BBT. Experiment 3: Rats were divided into two groups that were subjected to 30days of standard conditions or environmental enrichment (EE); from days 25 to 30, all rats received a fixed dose of progesterone (0.5mg/rat, s.c.) or vehicle. On day 31, the rats were tested with BBT. Results showed that PW increased anxiety in both strains, and fluoxetine prevented anxiety in WKY rats. In contrast, a gradual reduction of progesterone prevents the anxiety in Wistar but not in WKY. EE was preventive against the anxiety induced by PW in both strains of rats. Thus, the results suggest that anxiety induced by PW is prevented by EE while the anxiolytic effect of pharmacological treatments depends on stress vulnerability.

  12. 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

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

    PubMed

    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.

  14. Hypertensive rats are susceptible to TLR4-mediated signaling following exposure to combustion source particulate matter.

    PubMed

    Gilmour, Peter S; Schladweiler, Mette C; Richards, Judy H; Ledbetter, Allen D; Kodavanti, Urmila P

    2004-01-01

    Toll-like receptor 4 (TLR4) has been shown to play a role in cell signaling that results in neutrophilic inflammation in response to lipopolysaccharide and respiratory syncytial virus infection. TLR4 also interacts with CD14, which upon complex formation triggers TLR4-associated signaling pathways to produce a proinflammatory response. This mechanism results in the activation of NF-kappa B and subsequent inflammatory gene induction. In order to determine the effect of combustion source particle matter (PM), rich in zinc and nickel but with negligible endotoxin, on a possible activation of TLR4-mediated cell signaling and inflammation, we intratracheally (IT) instilled 3.3 mg/kg of PM into 12-w-old healthy male Wistar Kyoto (WKY) and susceptible spontaneously hypertensive (SH) rats. Inflammation, inflammatory-mediator gene expression, bronchoalveolar lavage fluid (BALF) protein and LDH, TLR4 and CD14 protein, and NF-kappa B activation in the lung were determined after 24 h. Dose-response data (0.0, 0.83, 3.33, and 8.3 mg/kg PM) for BALF LDH were obtained as a marker of lung cell injury in SH rats. BALF neutrophils, but not macrophages, were significantly increased in the PM-exposed WKY and SH rats. SH rats showed a greater PMN increase than WKY rats. Similarly, BALF protein and LDH levels were also increased following PM exposure but to a significantly greater extent in SH rats. Plasma fibrinogen was increased only in SH rats exposed to PM. The increased inflammation seen in PM-exposed SH rats was accompanied by a significant increase in TLR4 protein in the lung tissue, which was primarily localized in alveolar macrophages and epithelial cells. CD14 was also increased by PM exposure in both SH and WKY rats but was significantly greater in the SH rats. These increases were associated with greater translocation of NF-kappa B in the lungs of SH rather than WKY rats. This was accompanied by increased macrophage inhibitory protein (MIP)-2 mRNA expression at 24 h of

  15. 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

  16. 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.

  17. 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

  18. Differences between rat strains in the development of PRL-secreting pituitary tumors with long-term estrogen treatment: In vitro insulin-like growth factor-1-induced lactotroph proliferation and gene expression are affected in Wistar-Kyoto rats with low estrogen-susceptibility.

    PubMed

    Mitsui, Tetsuo; Ishida, Maho; Izawa, Michi; Arita, Jun

    2013-01-01

    There are differences in the susceptibility of rat strains to pituitary growth and lactotroph proliferation caused by long-term treatment with estrogens. To investigate the pituitary mechanism for this strain difference in estrogen-induced lactotroph proliferation, we compared the abilities of 17-β estradiol (E2) and insulin-like growth factor-1 (IGF-1) to modulate lactotroph proliferation and gene expression in vitro in Wistar and Wistar-Kyoto (WKY) rats. These two strains of rats have a high and very low susceptibility to estrogen, respectively. Long-term in vivo treatment with E2 was confirmed to markedly increase pituitary weight and lactotroph proliferation in ovariectomized Wistar, but not in WKY rats. Pituitary lactotrophs in primary cultures showed similar proliferative responsiveness to the culture condition-dependent, stimulatory and inhibitory actions of E2 in both strains. The only difference in lactotroph proliferation in vitro was a lower response to IGF-1 in WKY cells compared with Wistar cells. This difference in proliferation was associated with strain differences in IGF-1-induced gene expression in Wistar and WKY cultured cells. Of the genes tested, IGF-1-induced expression of the Wnt4, Stc1, Mybl1, and Myc genes was attenuated or abolished in WKY cells. These results suggest that the proliferative response to estrogen in lactotrophs in primary culture does not reflect the proliferative response to long-term estrogen treatment observed in vivo in Wistar and WKY rats. The strain difference in proliferation and gene expression to IGF-1 may be implicated in the variable degree of susceptibility for lactotroph proliferation observed in different strains of rats following long-term estrogen treatment.

  19. The Long-Term Effect of Radical Prostatectomy on Erectile Function, Urinary Continence, and Lower Urinary Tract Symptoms: A Comparison to Age-Matched Healthy Controls

    PubMed Central

    Ponholzer, Anton; Augustin, Herbert; Madersbacher, Stephan; Pummer, Karl

    2017-01-01

    Introduction. To analyze the impact of radical prostatectomy (RPE) on erectile function and lower urinary tract function in comparison to age-matched healthy men. Materials and Methods. Patients who underwent radical retropubic prostatectomy completed questionnaires containing the IIEF-5, the Bristol female LUTS questionnaire, and the International Prostate Symptom Score (IPSS). Results. Patients after RPE were included (n = 363). Age-matched healthy men (n = 363) were included. The mean IIEF-5 of patients aged 61–70 yrs after RPE was 10.4 ± 6.6 versus 18.8 ± 5.3 in the control cohort; the respective values for men aged 71–80 yrs after RPE were 7.2 ± 6.5 versus 13.6 ± 7.7 in the control cohort. Urinary incontinence after RPE was reported in 41.9% (61–70 years) and 37.7% (71–80) versus 7.5% and 15.1% in the control cohort. The mean IPSS of patients after RPE aged 61–70 yrs was 5.0 ± 4.4 versus 5.5 ± 4.9 in the control cohort; the respective values for men aged 71–80 yrs were 6.0 ± 4.9 versus 7.5 ± 5.7 in the healthy cohort. Conclusions. The negative effect of radical prostatectomy on erectile and urinary incontinence remains substantial. The physiologically declining erectile and lower urinary tract function with ageing reduces the difference between healthy men and those after surgery. Healthy men have a higher IPSS presumably due to the presence of bladder outlet obstruction. PMID:28261619

  20. Exercise performance and cardiovascular health variables in 70-year-old male soccer players compared to endurance-trained, strength-trained and untrained age-matched men.

    PubMed

    Randers, Morten Bredsgaard; Andersen, Jesper L; Petersen, Jesper; Sundstrup, Emil; Jakobsen, Markus D; Bangsbo, Jens; Saltin, Bengt; Krustrup, Peter

    2014-01-01

    The aim was to investigate performance variables and indicators of cardiovascular health profile in elderly soccer players (SP, n = 11) compared to endurance-trained (ET, n = 8), strength-trained (ST, n = 7) and untrained (UT, n = 7) age-matched men. The 33 men aged 65-85 years underwent a testing protocol including measurements of cycle performance, maximal oxygen uptake (VO2max) and body composition, and muscle fibre types and capillarisation were determined from m. vastus lateralis biopsy. In SP, time to exhaustion was longer (16.3 ± 2.0 min; P < 0.01) than in UT (+48%) and ST (+41%), but similar to ET (+1%). Fat percentage was lower (P < 0.05) in SP (-6.5% points) than UT but not ET and ST. Heart rate reserve was higher (P < 0.05) in SP (104 ± 16 bpm) than UT (+21 bpm) and ST (+24 bpm), but similar to ET (+2 bpm), whereas VO2max was not significantly different in SP (30.2 ± 4.9 ml O2 · min(-1) · kg(-1)) compared to UT (+14%) and ST (+9%), but lower (P < 0.05) than ET (-22%). The number of capillaries per fibre was higher (P < 0.05) in SP than UT (53%) and ST (42%) but similar to ET. SP had less type IIx fibres than UT (-12% points). In conclusion, the exercise performance and cardiovascular health profile are markedly better for lifelong trained SP than for age-matched UT controls. Incremental exercise capacity and muscle aerobic capacity of SP are also superior to lifelong ST athletes and comparable to endurance athletes.

  1. 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 ...

  2. Dietary borage oil alters plasma, hepatic and vascular tissue fatty acid composition in spontaneously hypertensive rats.

    PubMed

    Engler, M M; Engler, M B

    1998-07-01

    Dietary borage oil rich in gamma-linolenic acid (GLA) has been shown to lower blood pressure in Wistar Kyoto (WKY) and spontaneously hypertensive rats (SHR). A potential mechanism for this effect may be attributed to changes in metabolism of GLA to dihomogamma-linolenic (DGLA) and arachidonic acids (AA). We investigated the effects of dietary borage oil on fatty acid composition in the plasma, liver and vascular tissue in WKY and SHR. The diet significantly increased the levels of omega-6 polyunsaturated fatty acids. GLA and DGLA levels in the plasma, liver, aorta and renal artery tissues increased in SHR (P < 0.001) and WKY (P < 0.001). AA levels were also increased in both plasma and liver of SHR (P < 0.05) and WKY (P < 0.05) fed the borage oil enriched diet. The results demonstrate that dietary borage oil produces marked changes in the metabolism of GLA which may contribute to its blood pressure lowering effect in WKY and SHR.

  3. Effects of nimodipine on learning in normotensive and spontaneously hypertensive rats.

    PubMed

    Meneses, A; Terrón, J A; Ibarra, M; Hong, E

    1997-04-01

    It is well known that the calcium channel blocker, nimodipine, has beneficial effects on learning in either aged or hypertensive animals and humans. However, no attempts have been made to investigate if nimodipine can reverse the synergistic deleterious effects of aging and hypertension in the same subject. Therefore, this study investigated the effects of stable infusions of nimodipine in the autoshaping learning task using middle-aged normotensive (WKY) and hypertensive (SHR) rats. WKY and SHR of 12 months of age were implanted with osmotic minipumps releasing either vehicle or nimodipine (0.4 mg/kg/day). After 3 weeks of treatment, the animals received autoshaping training sessions during 4 consecutive days. The WKY animals treated with nimodipine exhibited the highest levels of learning during the last session, the rank order being WKY-nimodipine > SHR-nimodipine > WKY-vehicle > SHR-vehicle. These results confirm that nimodipine can reverse the impairing effects of either aging or hypertension on learning; the presence of both conditions, however, might produce more severe dysfunctional changes that cannot be totally reversed by nimodipine.

  4. 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.

  5. 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.

  6. Mapping of a quantitative trait locus for blood pressure on rat chromosome 2.

    PubMed Central

    Deng, A Y; Dene, H; Rapp, J P

    1994-01-01

    A genetic map for rat chromosome 2 that includes five candidate genes for blood pressure regulation was constructed in a region containing a quantitative trait locus (QTL) for blood pressure. Two F2 populations of male rats raised on high salt (8% NaCI) diet from weaning were studied: F2(WKY x S), derived from a cross of Dahl salt-sensitive rats (S) and Wistar-Kyoto rats (WKY); and F2(MNS x S), derived from a cross of S rats and Milan normotensive strain (MNS). In both populations a blood pressure QTL was localized between Na+,K(+)-ATPase alpha 1 isoform and calmodulin-dependent protein kinase II-delta loci. The LOD score for existence of this blood pressure QTL based on the combined populations (n = 330) was 5.66 and accounted for 9.2% of the total variance and 26% of the genetic variance. PMID:8040284

  7. Soy-derived phytoestrogens as preventive and acute neuroprotectors in experimental ischemic stroke: influence of rat strain.

    PubMed

    Castelló-Ruiz, M; Torregrosa, G; Burguete, M C; Salom, J B; Gil, J V; Miranda, F J; Jover-Mengual, T; Marrachelli, V G; Alborch, E

    2011-04-15

    The ability of a soy-based high-phytoestrogen diet (nutritional intervention) or genistein (pharmacological intervention), to limit ischemic brain damage in Wistar, Wistar-Kyoto (WKY) and spontaneously hypertensive (SHR) rats, has been assessed. As to the nutritional intervention, two groups from each strain received either a phytoestrogen-free (PE-0) or a high-phytoestrogen (PE-600) diet from weaning to adulthood. As to the pharmacological intervention, all animals were fed the standard soy-free AIN-93G diet and subsequently separated into two groups from each strain to receive either pure genistein (aglycone form, 1mg/kg/day intraperitoneal) or vehicle at 30 min reperfusion. After an episode of 90 min ischemia (intraluminal thread procedure) followed by 3 days reperfusion, cerebral infarct volume was measured. Arterial blood pressure (ABP) was significantly higher at the basal stage (just before ischemia) in SHR (140 ± 7 mmHg, n=17, p<0.05) than in Wistar (113 ± 4mmHg, n=23) and WKY (111 ± 6mmHg, n=14) rats. No significant differences were shown among the three stages (basal, ischemia, reperfusion) within each rat strain for both PE-0 and PE-600 diets. Wistar, but not WKY or SHR, rats fed the PE-600 diet showed significantly lower infarct volumes than their counterparts fed the PE-0 diet (30 ± 3% vs. 17 ± 3%, p<0.01). Genistein-treated Wistar, but not WKY or SHR, rats showed significantly lower infarct volumes than their vehicle-treated controls (27 ± 2% vs. 15 ± 2%, p<0.01). Our results demonstrate that: (1) the neuroprotective action of either chronic or acute exposure to soy isoflavones is strain-dependent, since it was shown in Wistar but not WKY or SHR rats; and (2) the soy-based diet does not prevent development of hypertension in SHR rats.

  8. Impact of genetic strain on body fat loss, food consumption, metabolism, ventilation, and motor activity in free running female rats.

    PubMed

    Gordon, C J; Phillips, P M; Johnstone, A F M

    2016-01-01

    Chronic exercise is considered as one of the most effective means of countering symptoms of the metabolic syndrome (MS) such as obesity and hyperglycemia. Rodent models of forced or voluntary exercise are often used to study the mechanisms of MS and type 2 diabetes. However, there is little known on the impact of genetic strain on the metabolic response to exercise. We studied the effects of housing rats with running wheels (RW) for 65 days compared to sedentary (SED) housing in five female rat strains: Sprague-Dawley (SD), Long-Evans (LE), Wistar (WIS), spontaneously hypertensive (SHR), and Wistar-Kyoto (WKY). Key parameters measured were total distance run, body composition, food consumption, motor activity, ventilatory responses by plethysmography, and resting metabolic rate (MR). WKY and SHR ran significantly more than the WIS, LE, and SD strains. Running-induced reduction in body fat was affected by strain but not by distance run. LE's lost 6% fat after 21 d of running whereas WKY's lost 2% fat but ran 40% more than LE's. LE and WIS lost body weight while the SHR and WKY strains gained weight during running. Food intake with RW was markedly increased in SHR, WIS, and WKY while LE and SD showed modest increases. Exploratory motor activity was reduced sharply by RW in all but the SD strain. Ventilatory parameters were primarily altered by RW in the SHR, WKY, and WIS strains. MR was unaffected by RW. In an overall ranking of physiological and behavioral responses to RW, the SD strain was considered the least responsive whereas the WIS was scored as most responsive. In terms of RW-induced fat loss, the LE strain appears to be the most ideal. These results should be useful in the future selection of rat models to study benefits of volitional exercise.

  9. Reduced contraction strength with increased intracellular [Ca2+] in left ventricular trabeculae from failing rat hearts

    PubMed Central

    Ward, Marie-Louise; Pope, Adèle J; Loiselle, Denis S; Cannell, Mark B

    2003-01-01

    Intracellular calcium ([Ca2+]i) and isometric force were measured in left ventricular (LV) trabeculae from spontaneously hypertensive rats (SHR) with failing hearts and normotensive Wistar-Kyoto (WKY) controls. At a physiological stimulation frequency (5 Hz), and at 37 °C, the peak stress of SHR trabeculae was significantly (P ≤; 0.05) reduced compared to WKY (8 ± 1 mN mm−2(n = 8)vs. 21 ± 5 mN mm−2(n = 8), respectively). No differences between strains in either the time-to-peak stress, or the time from peak to 50 % relaxation were detected. Measurements using fura-2 showed that in the SHR both the peak of the Ca2+ transient and the resting [Ca2+]i were increased compared to WKY (peak: 0.69 ± 0.08 vs. 0.51 ± 0.08 μm (P ≤ 0.1) and resting: 0.19 ± 0.02 vs. 0.09 ± 0.02 μm (P ≤ 0.05), SHR vs. WKY, respectively). The decay of the Ca2+ transient was prolonged in SHR, with time constants of: 0.063 ± 0.002 vs. 0.052 ± 0.003 s (SHR vs. WKY, respectively). Similar results were obtained at 1 Hz stimulation, and for[Ca2+]o between 0.5 and 5 mm. The decay of the caffeine-evoked Ca2+ transient was slower in SHR (9.8 ± 0.7 s (n = 8)vs. 7.7 ± 0.2 s (n = 8) in WKY), but this difference was removed by use of the SL Ca2+-ATPase inhibitor carboxyeosin. Histological examination of transverse sections showed that the fractional content of perimysial collagen was increased in SHR compared to WKY (18.0 ± 4.6 % (n = 10)vs. 2.9 ± 0.9 % (n = 11) SHR vs. WKY, respectively). Our results show that differences in the amplitude and the time course of the Ca2+ transient between SHR and WKY do not explain the reduced contractile performance of SHR myocardium per se. Rather, we suggest that, in this animal model of heart failure, contractile function is compromised by increased collagen, and its three-dimensional organisation, and not by reduced availability of intracellular Ca2+. PMID:12527740

  10. Genetic Dissection of a Blood Pressure Quantitative Trait Locus on Rat Chromosome 1 and Gene Expression Analysis Identifies SPON1 as a Novel Candidate Hypertension Gene

    PubMed Central

    Clemitson, Jenny-Rebecca; Dixon, Richard J.; Haines, Steve; Bingham, Andrew J.; Patel, Bhakti R.; Hall, Laurence; Lo, Ming; Sassard, Jean; Charchar, Fadi J.; Samani, Nilesh J.

    2007-01-01

    A region with a major effect on blood pressure is located on rat chromosome 1. We have previously isolated this region in reciprocal congenic strains (WKY.SHR-Sa and SHR.WKY-Sa) derived from a cross of the spontaneously hypertensive rat (SHR) with the Wistar-Kyoto rat (WKY) and shown that there are two distinct BP quantitative trait loci (QTLs), BP1 and BP2, in this region. Sisa1, a congenic sub-strain from the SHR.WKY-Sa animals carrying an introgressed segment of 4.3Mb, contains BP1. Here, we report further dissection of BP1 by the creation of two new mutually exclusive congenic sub-strains (Sisa1a and Sisa1b) and interrogation of candidate genes by expression profiling and targeted transcript sequencing. Only one of the sub-strains (Sisa1a) continued to demonstrate a BP difference but with a reduced introgressed segment of 3Mb. Exonic sequencing of the twenty genes located in the Sisa1a region did not identify any major differences between SHR and WKY. However, microarray expression profiling of whole kidney samples and subsequent quantitative RT-PCR identified a single gene, Spon1 that exhibited significant differential expression between the WKY and SHR genotypes at both 6 and 24 weeks of age. Western blot analysis confirmed an increased level of the Spon1 gene product in SHR kidneys. Spon1 belongs to a family of genes with anti-angiogenic properties. These findings justify further investigation of this novel positional candidate gene in BP control in hypertensive rat models and humans. PMID:17332427

  11. Unique Regulatory Properties of Mesangial Cells Are Genetically Determined in the Rat

    PubMed Central

    Lai, Ping-Chin; Chiu, Ling-Yin; Srivastava, Prashant; Trento, Cristina; Dazzi, Francesco; Petretto, Enrico; Cook, H. Terence; Behmoaras, Jacques

    2014-01-01

    Mesangial cells are glomerular cells of stromal origin. During immune complex mediated crescentic glomerulonephritis (Crgn), infiltrating and proliferating pro-inflammatory macrophages lead to crescent formation. Here we have hypothesised that mesangial cells, given their mesenchymal stromal origin, show similar immunomodulatory properties as mesenchymal stem cells (MSCs), by regulating macrophage function associated with glomerular crescent formation. We show that rat mesangial cells suppress conA-stimulated splenocyte proliferation in vitro, as previously shown for MSCs. We then investigated mesangial cell-macrophage interaction by using mesangial cells isolated from nephrotoxic nephritis (NTN)-susceptible Wistar Kyoto (WKY) and NTN-resistant Lewis (LEW) rats. We first determined the mesangial cell transcriptome in WKY and LEW rats and showed that this is under marked genetic control. Supernatant transfer results show that WKY mesangial cells shift bone marrow derived macrophage (BMDM) phenotype to M1 or M2 according to the genetic background (WKY or LEW) of the BMDMs. Interestingly, these effects were different when compared to those of MSCs suggesting that mesangial cells can have unique immunomodulatory effects in the kidney. These results demonstrate the importance of the genetic background in the immunosuppressive effects of cells of stromal origin and specifically of mesangial cell-macrophage interactions in the pathophysiology of crescentic glomerulonephritis. PMID:25343449

  12. 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

  13. The effects of running exercise on oxidative capacity and PGC-1α mRNA levels in the soleus muscle of rats with metabolic syndrome.

    PubMed

    Nagatomo, Fumiko; Fujino, Hidemi; Kondo, Hiroyo; Kouzaki, Motoki; Gu, Ning; Takeda, Isao; Tsuda, Kinsuke; Ishihara, Akihiko

    2012-03-01

    Skeletal muscles in animals with metabolic syndrome exhibit reduced oxidative capacity. We investigated the effects of running exercise on fiber characteristics, oxidative capacity, and mRNA levels in the soleus muscles of rats with metabolic syndrome [SHR/NDmcr-cp (cp/cp); CP]. We divided 5-week-old CP rats into non-exercise (CP) and exercise (CP-Ex) groups. Wistar-Kyoto rats (WKY) were used as the control group. CP-Ex rats were permitted voluntary exercise on running wheels for 10 weeks. Triglyceride levels were higher and adiponectin levels lower in the CP and CP-Ex groups than in the WKY group. However, triglyceride levels were lower and adiponectin levels higher in the CP-Ex group than in the CP group. The soleus muscles in CP-Ex rats contained only high-oxidative type I fibers, whereas those in WKY and CP rats contained type I, IIA, and IIC fibers. Muscle succinate dehydrogenase (SDH) activity was higher in the CP-Ex group than in the CP group; there was no difference in SDH activity between the WKY and CP-Ex groups. Muscle proliferator-activated receptor γ coactivator-1α (PGC-1α) mRNA levels were higher in the CP-Ex group than in the CP group; there was no difference in PGC-1α mRNA levels between the WKY and CP-Ex groups. In CP-Ex rats, longer running distance was associated with increased muscle SDH activity and PGC-1α mRNA levels. We concluded that running exercise restored decreased muscle oxidative capacity and PGC-1α mRNA levels and improved hypertriglyceridemia in rats with metabolic syndrome.

  14. Brief Social Isolation in the Adolescent Wistar-Kyoto Rat Model of Endogenous Depression Alters Corticosterone and Regional Monoamine Concentrations.

    PubMed

    Shetty, Reshma A; Sadananda, Monika

    2017-02-24

    The Wistar-Kyoto rat (WKY) model has been suggested as a model of adult and adolescent depression though face, predictive and construct validities of the model to depression remain equivocal. The suitability of the WKY as a diathesis model that tests the double-hit hypothesis, particularly during critical periods of brain and behavioural development remains to be established. Here, effects of post-weaning social isolation were assessed during early adolescence (~30pnd) on behavioural despair and learned helplessness in the forced swim test (FST), plasma corticosterone levels and tissue monoamine concentrations in brain areas critically involved in depression, such as prefrontal cortex, nucleus accumbens, striatum and hippocampus. Significantly increased immobility in the FST was observed in socially-isolated, adolescent WKY with a concomitant increase in corticosterone levels over and above the FST-induced stress. WKY also demonstrated a significantly increased release and utilization of dopamine, as manifested by levels of metabolites 3,4-dihydroxyphenylacetic acid and homovanillic acid in nucleus accumbens, indicating that the large dopamine storage pool evident during adolescence induces greater dopamine release when stimulated. The serotonin metabolite 5-hydroxy-indoleacetic acid was also significantly increased in nucleus accumbens, indicating increased utilization of serotonin, along with norepinephrine levels which were also signficantly elevated in socially-isolated adolescent WKY. Differences in neurochemistry suggest that social or environmental stimuli during critical periods of brain and behavioural development can determine the developmental trajectories of implicated pathways.

  15. Norepinephrine-induced relaxations in rat aorta mediated by endothelial beta adrenoceptors. Impairment by ageing and hypertension.

    PubMed

    Arribas, S; Marín, J; Ponte, A; Balfagón, G; Salaices, M

    1994-08-01

    The objective of the present work has been to analyze the influence of endothelium, ageing and hypertension in the norepinephrine (NE)-induced responses. For this purpose we used aortic rings from spontaneously hypertensive (SHR) and Wistar-Kyoto (WKY) rats of different ages. In rings with endothelium from 5-week-old WKY, cumulative addition of NE (0.01 and 0.1 microM) caused concentration-dependent contractions, whereas higher concentrations (1 and 10 microM) induced concentration-dependent relaxations. In 5-week-old SHR and 3-month-old WKY rats, these relaxant responses were observed only at 10 microM NE, and they disappeared in older animals from both strains. In endothelium denuded rings, NE induced only contractions, which were similar in WKY rats of different ages, but significantly increased in 6- and 12-month-old SHR. In both strains, the endothelium-dependent relaxant responses to NE were abolished by NG-nitro-L-arginine methyl ester and propranolol, but not modified by yohimbine or ouabain. Isoproterenol (0.01-10 microM) induced concentration-dependent vasodilation in rings from 5-week-old rats of both strains, precontracted with 1 microM NE. Isoproterenol-elicited responses were reduced by endothelium removal or by 0.1 mM NG-nitro-L-arginine methyl ester and abolished by 1 microM propranolol. These results suggest that: 1) in the aorta from young WKY and prehypertensive SHR rats, NE induces vasodilations mediated by activation of endothelial beta adrenoceptors and release of nitric oxide; 2) these responses are impaired during ageing and hypertension; and 3) there is an important negative endothelial modulation of NE-induced contraction in adult SHR rats.

  16. Confirming the cognition of rising scores: Fox and Mitchum (2013) predicts violations of measurement invariance in series completion between age-matched cohorts.

    PubMed

    Fox, Mark C; Mitchum, Ainsley L

    2014-01-01

    The trend of rising scores on intelligence tests raises important questions about the comparability of variation within and between time periods. Descriptions of the processes that mediate selection of item responses provide meaningful psychological criteria upon which to base such comparisons. In a recent paper, Fox and Mitchum presented and tested a cognitive theory of rising scores on analogical and inductive reasoning tests that is specific enough to make novel predictions about cohort differences in patterns of item responses for tests such as the Raven's Matrices. In this paper we extend the same proposal in two important ways by (1) testing it against a dataset that enables the effects of cohort to be isolated from those of age, and (2) applying it to two other inductive reasoning tests that exhibit large Flynn effects: Letter Series and Word Series. Following specification and testing of a confirmatory item response model, predicted violations of measurement invariance are observed between two age-matched cohorts that are separated by only 20 years, as members of the later cohort are found to map objects at higher levels of abstraction than members of the earlier cohort who possess the same overall level of ability. Results have implications for the Flynn effect and cognitive aging while underscoring the value of establishing psychological criteria for equating members of distinct groups who achieve the same scores.

  17. Influence of BMI on health-related quality of life: comparison between an obese adult cohort and age-matched population norms.

    PubMed

    Anandacoomarasamy, Ananthila; Caterson, Ian D; Leibman, Steven; Smith, Garett S; Sambrook, Phillip N; Fransen, Marlene; March, Lyn M

    2009-11-01

    The aim of this study was to determine health-related quality of life and fatigue measures in obese subjects and to compare scores with age- and gender-matched population norms. A total of 163 obese subjects were recruited from laparoscopic-adjustable gastric banding or exercise and diet weight loss programs between March 2006 and December 2007. All subjects completed the Medical Outcomes Study Short Form 36 (SF-36), Assessment of Quality of Life (AQoL), and Multidimensional Assessment of Fatigue (MAF) questionnaires. One-sample t-tests were used to compare transformed scores with age- and gender-matched population norms and controls. Obese subjects have significantly lower SF-36 physical and emotional component scores, significantly lower AQoL utility scores and significantly higher fatigue scores compared to age-matched population norms. Within the study cohort, the SF-36 physical functioning, role physical and bodily pain scores, and AQoL utility index were even lower in subjects with clinical knee osteoarthritis (OA). However, obese individuals without OA still had significantly lower scores compared to population norms. Obesity is associated with impaired health-related quality of life and disability as measured by the SF-36, AQoL, and fatigue score (MAF) compared to matched population norms.

  18. The fears, phobias and anxieties of children with autism spectrum disorders and Down syndrome: comparisons with developmentally and chronologically age matched children.

    PubMed

    Evans, David W; Canavera, Kristin; Kleinpeter, F Lee; Maccubbin, Elise; Taga, Ken

    2005-01-01

    This study compared the fears and behavior problems of 25 children with an autism spectrum disorder (ASD), 43 children with Down syndrome (DS), 45 mental age (MA) matched children, and 37 chronologically age (CA) matched children. Children's fears, phobias, anxieties and behavioral problems were assessed using parent reports. Significant differences emerged across the diagnostic groups on a variety of fears. Children with ASD were reported to have more situation phobias and medical fears, but fewer fears of harm/injury compared to all other groups. The groups also differed in terms of the pattern of correlations between fears, phobias, anxieties and behavior problems. For children with ASD, fears, phobias and anxieties were closely related to problem behaviors, whereas fears, phobias, and anxieties were less related to behavioral symptoms for the other groups of subjects. Such findings suggest that children with ASD exhibit a distinct profile of fear and anxiety compared to other mental age and chronologically age-matched children, and these fears are related to the symptoms associated with ASD.

  19. Comparison of constitutive gene expression levels of hepatic cholesterol biosynthetic enzymes between Wistar-Kyoto and stroke-prone spontaneously hypertensive rats.

    PubMed

    Nemoto, Kiyomitsu; Ikeda, Ayaka; Ito, Sei; Miyata, Misaki; Yoshida, Chiaki; Degawa, Masakuni

    2013-01-01

    Serum total cholesterol amounts in the stroke-prone hypertensive rat (SHRSP) strain are lower than in the normotensive control strain, Wistar-Kyoto (WKY) rat. To understand the strain difference, constitutive gene expression levels of hepatic cholesterol biosynthetic enzymes in male 8-week-old SHRSP and WKY rats were comparatively examined by DNA microarray and real-time reverse transcription-polymerase chain reaction (RT-PCR) analyses. Of 22 cholesterol biosynthetic enzyme genes, expression levels of 8 genes, Pmvk, Idi1, Fdps, Fdft1, Sqle, Lss, Sc4mol, and Hsd17b7, in SHRSP were less than 50% those of the WKY rats; especially, the expression level of Sqle gene, encoding squalene epoxidase, a rate-limiting enzyme in cholesterol biosynthesis pathway, was about 20%. The gene expression level of sterol regulatory element-binding protein-2 (SREBP-2), which functions as a transcription factor upregulating gene expression of cholesterol biosynthetic enzymes, in SHRSP was about 70% of that in WKY rats. These results demonstrate the possibility that the lower serum total cholesterol level in SHRSP is defined by lower gene expression of most hepatic cholesterol biosynthetic enzymes. In particular, decreased gene expression level of Sqle gene might be the most essential factor. Moreover, the broad range of lowered rates of these genes in SHRSP suggests that the abnormal function and/or expression not only of SREBP-2 but also of one or more other transcription factors for those gene expressions exist in SHRSP.

  20. Heterogeneity of histamine H3 receptor genomic expression in the cerebral cortex of spontaneously hypertensive rat.

    PubMed

    Shaw, J B; Cai, Q; Mtshali, C; Myles, E L; Washington, B

    2007-05-15

    Specific binding of [3H]-N-alpha-methylhistamine to homogenates from cerebral cortex tissue was analyzed in aged Wistar Kyoto (WKY) and Spontaneously Hypertensive rats (SHR). Scatchard plot analysis of [3H]-N-alpha-methylhistamine binding of the H3 receptor in the cerebral cortex from aged (6, 9, 12, and 16 week) SHR animals indicated that Bmax increased, respectively, 38.05 +/- 1.58, 59.63 +/- 2.48, 79.17 +/- 5.02, and 84.41 +/- 3.72 fmol/mg of protein. Binding studies using tissue from WKY rats indicated that maximal binding (Bmax) of the ligand to the receptor was not significantly altered. The analyses also yielded Kd values of 5, 7.2, 6.3 and 3.8 nM in SHR tissue respectively. Primers based on the sequence of the third intracellular loop of the H3 receptor were amplified at 35 cycles yielding several amplicons. These amplicons expressed sizes 875, 485, and 280 bp in 6 and 9 week cortical tissue from WKY animals where as in cortical tissue from 6 and 9 week SHR animals only two amplicons were expressed, 485 and 280 bp, respectively. Differences in gene expression for 12 and 16 week WKY and SHR rats were also compared using identical primers. Five amplicons were expressed in cortical tissue from 12 and 16 week WKY rats with 1000, 900, 821, 485, and 430 bp where as in 12 and 16 week SHR animals only one amplicon was expressed at 485 bp. The present results imply (1) that H3 receptor density in cortical tissue of SHR animals increases with age where as the number of the expressed amplicons of the detected H3 receptor decreases; and (2) even though a decrease in number of expressed amplicons of the H3 receptor were observed, an increase in expression of the larger amplicon (~500 bp) is evident.

  1. Morphine Analgesia Modification in Normotensive and Hypertensive Female Rats after Repeated Fluoxetine Administration.

    PubMed

    Kosiorek-Witek, Anna; Makulska-Nowak, Helena Elżbieta

    2016-01-01

    The purpose of this investigation was to determine through the use of fluoxetine the effect of administering a serotonin reuptake inhibitor over several days on the antinociceptive action of μ-morphine type opioid receptor agonist. Investigations were performed on rats of both sexes, both the WKY normotensive strains as well as on the SHR genetically conditioned hypertensive strains. Results showed that the efficacy of morphine analgesia is higher in the SHR strain compared to normotensive rats (WKY). Surprisingly, repeated administration of fluoxetine reduced morphine analgesia, with the weakening of opioid antinociceptive action comparable to the duration of serotonin reuptake inhibitor administration. It was also concluded that the antinociceptive action of morphine in female rats and the alteration of its efficacy as a result of fluoxetine premedication for several days depend on oestrus cycle phase. The highest sensitivity of female rats to morphine was reported in the dioestrus and oestrus phases; much lower values were reported for the metoestrus phase.

  2. Interaction Between the Effects of Corticotropin-Releasing Factor and Prepulse Parameters on Prepulse Inhibition in Two Inbred Rat Strains and the F1 Generation of a Cross Between Them

    PubMed Central

    Conti, Lisa H.; Sutherland, Jane E.; Muhlhauser, Carey M.

    2009-01-01

    Levels of prepulse inhibition (PPI) depend on the interval between the startling and prepulse stimuli. Brown Norway rats show less PPI of the acoustic startle response than Wistar-Kyoto (WKY) rats when the interval between the prepulse and startling stimulus is 100 msec. Central administration of corticotropin-releasing factor (CRF) decreases PPI at this inter-stimulus interval. Here, the effect of CRF on PPI over a range of inter-stimulus intervals was examined in WKY and BN rats, and in the F1 generation of a cross between them. Rats received an intracerebroventricular infusion of either saline or CRF 30 min prior to testing PPI. Test trials included startle stimulus alone trials, and trials on which a prepulse stimulus of either 6, 12, or 15 dB above background preceded the startling stimulus by either 20, 75, 100, 500 or 2000 msec. CRF decreased PPI in WKY rats at all inter-stimulus intervals and all prepulse intensities, while the effect of CRF on PPI in BN rats only occurred at intermediate intervals. BN and WKY rats showed different levels of PPI only at the intermediate intervals. Baseline PPI in the F1 rats resembled the WKY phenotype. The CRF-induced change in PPI in the F1 generation has some qualities of the effects in each of the progenitor strains. These results suggest that both the effect of rats strain and of CRF on PPI depend on the inter-stimulus interval, and that there is an interaction between prepulse stimulus intensity and the inter-stimulus interval. PMID:19373982

  3. Spatial learning/memory and social and nonsocial behaviors in the spontaneously hypertensive, Wistar-Kyoto and Sprague-Dawley rat strains.

    PubMed

    Ferguson, Sherry A; Cada, Amy M

    2004-03-01

    The Spontaneously Hypertensive rat (SHR) is often described as less behaviorally reactive than its normotensive strain, the Wistar-Kyoto (WKY), although results are somewhat inconsistent across studies. In part, this may be due to the lack of a definitive characterization of "reactivity." Still, results from identical behavioral tests of SHR and WKY across studies are sometimes conflicting. Further, few comparisons with other rodent strains are available and these might provide guidance in outlining the meaning of reactivity. Here, social and nonsocial behaviors and spatial learning and memory were measured in male and female SHR, WKY, and Sprague-Dawley (SD) rats. Systolic blood pressure measurements at adulthood confirmed hypertension in the SHR. Juvenile play behavior indicated that SHRs were more sensitive to the strain of their play partner than were the WKY or SD, playing less with different strain partners than with same strain partners. However, adult dominance behavior (restricted access in a water competition test) indicated no strain differences. The SHR appeared to exhibit attenuated acoustic startle relative to the WKY and SD and their prepulse inhibition was substantially less at higher prepulse decibel intensities; however, this decreased prepulse inhibition was not the result of decreased startle during the test. Anxiety-related behavior in the elevated plus maze was most prominent in the SD strain, possibly as a result of poorer motor coordination as measured by rotarod performance. Elevated plus maze behavior as well as motor coordination did not differ between the SHR and WKY strains. Performance in the NCTR complex maze and the Morris water maze was significantly better in the SHR. These results do not support hypotheses of decreased behavioral reactivity in the SHR strain. Rather, they suggest complex interactions between social and nonsocial environments and the behavioral capabilities and requirements of the rat strain.

  4. Data supporting the cardiac mitochondria calcium handling in female normotensive and spontaneously hypertensive rats

    PubMed Central

    Ciocci Pardo, Alejandro; Rinaldi, Gustavo J.; Mosca, Susana M.

    2016-01-01

    In association with the published article “Mitochondrial calcium handling in normotensive and spontaneously hypertensive rats: correlation with systolic blood pressure levels” [1], this data article contains information about calcium handling of cardiac mitochondria isolated from female of both rats strains (WKY and SHR). Dataset of mitochondrial permeability transition pore (mPTP) resistance to opening Ca2+-mediated, Ca2+ retention capacity (CRC), time constants and mitochondrial membrane potential (ΔΨm) are showed. PMID:26977446

  5. 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

  6. Impaired function of alpha-2 adrenoceptors in smooth muscle of mesenteric arteries from spontaneously hypertensive rats.

    PubMed

    Feres, T; Borges, A C; Silva, E G; Paiva, A C; Paiva, T B

    1998-11-01

    The alpha2-adrenoceptor function in mesenteric arteries of spontaneously hypertensive rats (SHR) was investigated by comparing membrane potential changes in response to adrenergic agonists in preparations from female SHR, Wistar-Kyoto (WKY) and normotensive Wistar rats (NWR). Resting membrane potential was found to be less negative in mesenteric arteries from SHR than in those from NWR and WKY. Apamin induced a decrease in the membrane potential of mesenteric artery rings without endothelium from NWR and WKY, but had no effects in those from SHR. Both UK 14,304 and adrenaline, in the presence of prazosin, induced a hyperpolarization that was significantly lower in de-endothelialized mesenteric rings from SHR than in those from NWR and WKY. In mesenteric rings with endothelium, however, similar hyperpolarization was observed in the three strains. In NWR mesenteric rings with endothelium the hyperpolarization induced by activation of alpha2-adrenoceptors was abolished by apamin, whereas in intact SHR mesenteric rings this hyperpolarization was slightly reduced by apamin and more efficiently reduced by Nomega-nitro-L-arginine. It is concluded that the activity of potassium channels coupled to alpha2-adrenoceptors is altered in the smooth muscle cells of SHR mesenteric arteries, contributing to their less negative membrane potential. On the other hand, the endothelial alpha2-receptors are functioning in mesenteric vessels from SHR and their stimulation induces a hyperpolarization mainly through the release of nitric oxide.

  7. 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

  8. Relevance of maintenance triple-drug immunosuppression to bridle the amplification of rat cytomegalovirus infection after experimental lung transplantation.

    PubMed

    Lehle, K; von Suesskind-Schwendi, M; Diez, C; Michl, M; Geissler, E K; Wottge, H U; Schmid, C; Hirt, S W

    2012-12-01

    Immunosuppressive therapy required to treat rejection after lung transplantation (LTx) contributes significantly to the pathogenesis of cytomegalovirus (CMV) infection and disease. In a weak allogeneic left LTx model in the rat (Fisher 344 [F344] to Wistar Kyoto [WKY] rats) we analyzed the influence of acute CMV infection on postoperative day (POD) 3, with application of standard triple-drug immunosuppression (TD-IS) (cyclosporin A, azathioprine, prednisolone) on late outcome after LTx. Native right lungs and syngeneic grafts (WKY to WKY) served as controls. Rats were sacrificed on POD 15, 30, 60, and 100. TD-IS completely prevented acute and chronic rejection in non-infected rats. Allografts of CMV-infected rats treated with TD-IS showed only mild perivascular infiltrations in 6/10 rats (POD 15 and 30), which persisted up to POD 100 in 4/10 rats. In the long-term course, mild isolated interstitial and alveolar changes were found in 40% of these animals. In conclusion, rat CMV infection partially neutralized the immunosuppressive effect of TD-IS. However, an amplification of CMV infection under TD-IS can be controlled and does not result in fatal outcome.

  9. Activation of mineralocorticoid receptors in the rostral ventrolateral medulla is involved in hypertensive mechanisms in stroke-prone spontaneously hypertensive rats.

    PubMed

    Nakagaki, Toshiaki; Hirooka, Yoshitaka; Matsukawa, Ryuichi; Nishihara, Masaaki; Nakano, Masatsugu; Ito, Koji; Hoka, Sumio; Sunagawa, Kenji

    2012-04-01

    Mineralocorticoid receptor (MR) is recognized as a target for therapeutic intervention in hypertension and heart failure. MRs in the central nervous system are thought to have an important role in blood pressure regulation. Thus, we examined whether activation of the MR pathway in the rostral ventrolateral medulla (RVLM) of the brainstem contributes to the neural mechanism of hypertension in stroke-prone spontaneously hypertensive rats (SHRSPs). We microinjected eplerenone, aldosterone or Na(+)-rich artificial cerebrospinal fluid (aCSF) into the RVLM of anesthetized Wistar-Kyoto (WKY) rats and SHRSPs. Arterial pressure (AP), heart rate (HR) and renal sympathetic nerve activity (RSNA) were recorded. The expressions of the MR protein and the serum- and glucocorticoid-regulated kinase protein (Sgk1), which is a marker of MR activity, in the RVLM were measured by western blot analysis. Bilateral microinjection of eplerenone into the RVLM decreased AP and RSNA in WKY rats and SHRSPs, and the decreases in those variables were significantly greater in SHRSPs than WKY rats. Microinjection of aldosterone or Na(+)-rich aCSF into the RVLM increased AP and RSNA dose-dependently. The increases in those variables were significantly greater in SHRSPs than in WKY rats. The pressor responses of aldosterone or Na(+)-rich aCSF were attenuated by the prior injection of eplerenone in SHRSPs. Sgk1 expression levels in the RVLM were significantly greater in SHRSPs than in WKY rats. These findings suggest that activation of MRs in the RVLM enhances sympathetic activity, thereby contributing to the neural mechanism of hypertension in the SHRSP.

  10. Impromidine-induced changes in the permeability of the blood-brain barrier of normotensive and spontaneously hypertensive rats

    SciTech Connect

    Boertje, S.B.; Le Beau, D.; Ward, S. )

    1990-08-01

    Previous studies suggested histamine receptors mediate changes in the cerebrovascular permeability of rats. To test this, we investigated the effects of impromidine, a specific agonist at the histamine H2-receptor, on blood pressure and permeability of the blood-brain barrier (BBB). Impromidine produced dose-dependent hypotension in Wistar-Kyoto (WKY) and spontaneously hypertensive (SHR) rats. Two higher doses of impromidine increased BBB permeability to 99mTc-sodium pertechnetate in WKY rats; however, two lower doses decreased permeability in SHR rats. All doses of impromidine increased cerebrovascular permeability to 131I-labeled serum albumin in both species. Doses of the drug were 100 times greater than those required to produce similar alterations using histamine.

  11. 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.

  12. 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

    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.

  13. Identification of a nutrient-sensing transcriptional network in monocytes by using inbred rat models on a cafeteria diet

    PubMed Central

    Martínez-Micaelo, Neus; González-Abuín, Noemi; Terra, Ximena; Ardévol, Ana; Pinent, Montserrat; Petretto, Enrico; Blay, Mayte

    2016-01-01

    ABSTRACT Obesity has reached pandemic levels worldwide. The current models of diet-induced obesity in rodents use predominantly high-fat based diets that do not take into account the consumption of variety of highly palatable, energy-dense foods that are prevalent in Western society. We and others have shown that the cafeteria (CAF) diet is a robust and reproducible model of human metabolic syndrome with tissue inflammation in the rat. We have previously shown that inbred rat strains such as Wistar Kyoto (WKY) and Lewis (LEW) show different susceptibilities to CAF diets with distinct metabolic and morphometric profiles. Here, we show a difference in plasma MCP-1 levels and investigate the effect of the CAF diet on peripheral blood monocyte transcriptome, as powerful stress-sensing immune cells, in WKY and LEW rats. We found that 75.5% of the differentially expressed transcripts under the CAF diet were upregulated in WKY rats and were functionally related to the activation of the immune response. Using a gene co-expression network constructed from the genes differentially expressed between CAF diet-fed LEW and WKY rats, we identified acyl-CoA synthetase short-chain family member 2 (Acss2) as a hub gene for a nutrient-sensing cluster of transcripts in monocytes. The Acss2 genomic region is significantly enriched for previously established metabolism quantitative trait loci in the rat. Notably, monocyte expression levels of Acss2 significantly correlated with plasma glucose, triglyceride, leptin and non-esterified fatty acid (NEFA) levels as well as morphometric measurements such as body weight and the total fat following feeding with the CAF diet in the rat. These results show the importance of the genetic background in nutritional genomics and identify inbred rat strains as potential models for CAF-diet-induced obesity. PMID:27483348

  14. Identification of a nutrient-sensing transcriptional network in monocytes by using inbred rat models on a cafeteria diet.

    PubMed

    Martínez-Micaelo, Neus; González-Abuín, Noemi; Terra, Ximena; Ardévol, Ana; Pinent, Montserrat; Petretto, Enrico; Behmoaras, Jacques; Blay, Mayte

    2016-10-01

    Obesity has reached pandemic levels worldwide. The current models of diet-induced obesity in rodents use predominantly high-fat based diets that do not take into account the consumption of variety of highly palatable, energy-dense foods that are prevalent in Western society. We and others have shown that the cafeteria (CAF) diet is a robust and reproducible model of human metabolic syndrome with tissue inflammation in the rat. We have previously shown that inbred rat strains such as Wistar Kyoto (WKY) and Lewis (LEW) show different susceptibilities to CAF diets with distinct metabolic and morphometric profiles. Here, we show a difference in plasma MCP-1 levels and investigate the effect of the CAF diet on peripheral blood monocyte transcriptome, as powerful stress-sensing immune cells, in WKY and LEW rats. We found that 75.5% of the differentially expressed transcripts under the CAF diet were upregulated in WKY rats and were functionally related to the activation of the immune response. Using a gene co-expression network constructed from the genes differentially expressed between CAF diet-fed LEW and WKY rats, we identified acyl-CoA synthetase short-chain family member 2 (Acss2) as a hub gene for a nutrient-sensing cluster of transcripts in monocytes. The Acss2 genomic region is significantly enriched for previously established metabolism quantitative trait loci in the rat. Notably, monocyte expression levels of Acss2 significantly correlated with plasma glucose, triglyceride, leptin and non-esterified fatty acid (NEFA) levels as well as morphometric measurements such as body weight and the total fat following feeding with the CAF diet in the rat. These results show the importance of the genetic background in nutritional genomics and identify inbred rat strains as potential models for CAF-diet-induced obesity.

  15. 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

  16. 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

    2016-01-04

    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.

  17. Helium-induced cardioprotection of healthy and hypertensive rat myocardium in vivo.

    PubMed

    Oei, Gezina T M L; Huhn, Ragnar; Heinen, Andre; Hollmann, Markus W; Schlack, Wolfgang S; Preckel, Benedikt; Weber, Nina C

    2012-06-05

    Helium protects healthy myocardium against ischemia/reperfusion injury by early and late preconditioning (EPC, LPC) and postconditioning (PostC). We investigated helium-induced PostC of the hypertensive heart and enhancement by addition of LPC and EPC. We also investigated involvement of signaling kinases glycogen synthase kinase 3 beta (GSK-3β) and protein kinase C-epsilon (PKC-ε). To assess myocardial cell damage, we performed infarct size measurements in healthy Wistar Kyoto (WKY rats, n=8-9) and Spontaneous Hypertensive rats (SHR, n=8-9) subjected to 25 min ischemia and 120 min reperfusion. Rats inhaled 70% helium for 15 min after index ischemia (PostC), combined with 15 min helium 24h prior to index ischemia (LPC+PostC), a triple intervention with additional 3 short cycles of 5 min helium inhalation shortly before ischemia (EPC+LPC+PostC), or no further treatment. In WKY rats, PostC reduced infarct size from 46 ± 2% (mean ± S.E.M) in the control group to 29 ± 2%. LPC+PostC or EPC+LPC+PostC reduced infarct sizes to a similar extent (30 ± 3% and 32 ± 2% respectively). In SHR, EPC+LPC+PostC reduced infarct size from 53 ± 3% in control to 39 ± 3%, while PostC or LPC+PostC alone were not protective; infarct size 48 ± 4% and 44 ± 4%, respectively. Neither PostC in WKY rats nor EPC+LPC+PostC in SHR was associated with an increase in phosphorylation of GSK-3β and PKC-ε after 15 min of reperfusion. Concluding, a triple intervention of helium conditioning results in cardioprotection in SHR, whereas a single intervention does not. In WKY rats, the triple intervention does not further augment protection. Helium conditioning is not associated with a mechanism involving GSK-3β and PKC-ε.

  18. 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...

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

    PubMed

    Hsu, Hsinjen Julie; Bishop, Dorothy V M

    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 improvement, even

  20. In vivo visualization of characteristics of renal microcirculation in hypertensive and diabetic rats.

    PubMed

    Yamamoto, T; Tomura, Y; Tanaka, H; Kajiya, F

    2001-09-01

    We developed a videomicroscope system with a charge-coupled device camera and evaluated it in the investigation of the glomerular microcirculation in normal [Wistar-Kyoto (WKY)], spontaneously hypertensive (SHR), and streptoyotocin-induced diabetic rats (STZ). In WKY, the diameter of the afferent arterioles (Af) was 11.9 +/- 0.7 microm and that of the efferent arterioles (Ef) was 8.9 +/- 0.7 microm. Af and Ef in each glomerulus could be visualized simultaneously with continuous recording of blood pressure and renal blood flow. In SHR, Af diameter was constricted to approximately 60% of that in WKY. A dose-dependent dilation of Af and Ef was observed after administration of barnidipine (1-10 microg/kg iv), a calcium channel antagonist, in all three groups. No change was seen in the Af-to-Ef diameter ratio (Af/Ef ratio) in WKY. In SHR, the Af/Ef ratio increased significantly because of the marked dilation of Af after barnidipine administration. In contrast, barnidipine dilated Ef in STZ, causing a significant reduction in the Af/Ef ratio. This system can analyze in vivo glomerular microcirculation and systemic macrocirculation simultaneously, allowing more direct investigation of the characteristics of and acute changes in glomerular microcirculation in pathological animals.

  1. Na+/K+-ATPase alpha isoforms expression in stroke-prone spontaneously hypertensive rat heart ventricles: effect of salt loading and lacidipine treatment.

    PubMed

    Quintas, Luis Eduardo M; Noël, François; Wibo, Maurice

    2007-06-22

    Changes in myocardial expression of Na+/K+-ATPase alpha-subunit isoforms have been demonstrated in different models of cardiac hypertrophy and hypertension. Here we studied the expression of these isozymes in stroke-prone spontaneously hypertensive rats (SHRSP) and the influence of high salt diet and treatment with the dihydropyridine lacidipine. Adult SHRSP were offered either 1% NaCl or water as drinking solution for 6 weeks. Salt-loaded SHRSP were treated or not with 1 mg/kg/day lacidipine. Compared to Wistar Kyoto (WKY) rats, non-salt-loaded SHRSP presented significant hypertension and cardiac hypertrophy. Salt intake markedly enhanced cardiac hypertrophy, an effect blunted by lacidipine. [3H]Ouabain binding assays on total particulate fractions from heart ventricles revealed the existence of two high-affinity sites with Kd approximately 25 and approximately 200 nM, ascribed to the alpha3 and alpha2 isoforms, respectively. Bmax of alpha3 was unexpectedly high (40% of total high-affinity binding) in ventricles from WKY rats but very low in all groups of SHRSP. On the other hand, Bmax of alpha2 was similar in WKY and non-salt-loaded SHRSP; however, salt loading of SHRSP resulted in a Bmax reduction of 20% (P<0.05), an effect blocked by lacidipine. These effects were largely confirmed by immunoblotting analysis, which, in addition, demonstrated that the density of the ubiquitous alpha1 isoform was comparable among the experimental groups. In conclusion, WKY rats showed a high myocardial expression of the Na+/K+-ATPase alpha3 subunit, which was not found in SHRSP; the level of the alpha2 isoform was similar in untreated SHRSP and WKY; salt-loading of SHRSP promoted reduction of the alpha2 isoform, and this effect was completely hampered by lacidipine.

  2. A high-potassium diet reduces infarct size and improves vascular structure in hypertensive rats.

    PubMed

    Dorrance, Anne M; Pollock, David M; Romanko, Olga P; Stepp, David W

    2007-01-01

    High-potassium diets can improve vascular function, yet the effects of potassium supplementation on ischemic stroke have not been studied. We hypothesized that dietary potassium supplementation would reduce ischemic cerebral infarct size by reversing cerebral artery hypertrophy. Six-week-old male stroke-prone spontaneously hypertensive rats (SHRSP) were fed diets containing 0.79% potassium (LK) or 2.11% potassium (HK) for 6 wk; Wistar-Kyoto (WKY) rats were fed the LK diet. The HK diet did not reduce blood pressure, as measured by telemetry, in the SHRSP. Cerebral ischemia was induced by middle cerebral artery (MCA) occlusion. The resultant infarct was smaller in the HK-SHRSP than in the LK-SHRSP: 55.1 +/- 6.3 vs. 71.4 +/- 2.4% of the hemisphere infarcted (P < 0.05). Infarcts were smaller in WKY rats (33.5 +/- 4.8%) than in LK-SHRSP or HK-SHRSP. The vessel wall of MCAs from LK-SHRSP was hypertrophied compared with WKY rats; this was reversed in HK-SHRSP. RT-PCR analysis of the cerebral vessels showed that expression of platelet-derived growth factor receptors-alpha and -beta, epidermal growth factor receptor, and collagen I and III was increased in the vessels from LK-SHRSP compared with WKY rats and reduced in HK-SHRSP. These results suggest that potassium supplementation provides neuroprotection in a model of ischemic stroke independent of blood pressure and possibly through changes in vascular structure.

  3. Inhaled environmental combustion particles cause myocardial injury in the Wistar Kyoto rat.

    PubMed

    Kodavanti, Urmila P; Moyer, Carolyn F; Ledbetter, Allen D; Schladweiler, Mette C; Costa, Daniel L; Hauser, Russ; Christiani, David C; Nyska, Abraham

    2003-02-01

    Epidemiologists have associated particulate matter (PM) air pollution with cardiovascular morbidity and premature mortality worldwide. However, experimental evidence demonstrating causality and pathogenesis of particulate matter (PM)-induced cardiovascular damage has been insufficient. We hypothesized that protracted, repeated inhalation by rats of oil combustion-derived, fugitive emission PM (EPM), similar in metal composition to selected sources of urban air PM, causes exposure duration- and dose-dependent myocardial injury in susceptible rat strains. Zinc was the only primary water-leachable/bioavailable element of this EPM. Male Sprague-Dawley (SD), Wistar Kyoto (WKY), and spontaneously hypertensive (SH) rats were exposed nose-only to EPM (2, 5, or 10 mg/m(3), 6 h/day for 4 consecutive days or 10 mg/m(3), 6 h/day, 1 day/week for 4 or 16 consecutive weeks). Two days following the last EPM exposure, cardiac and pulmonary tissues were examined histologically. The results showed that particle-laden alveolar macrophages were the only pulmonary lesions observed in all three rat strains. However, WKY rats exposed to EPM (10 mg/m(3) 6 h/day, 1 day/week for 16 weeks) demonstrated cardiac lesions with inflammation and degeneration. To further characterize the nature of EPM-associated lesions, more rigorous histopathological and histochemical techniques were employed for WKY and SD rats. We examined the hearts for myocardial degeneration, inflammation, fibrosis, calcium deposits, apoptosis, and the presence of mast cells. Decreased numbers of granulated mast cells, and multifocal myocardial degeneration, chronic-active inflammation, and fibrosis were present in 5 of 6 WKY rats exposed to EPM for 16 weeks. None of these lesions were present in WKY exposed to clean air. EPM-related cardiac lesions were indistinguishable from air-exposed controls in SD and SH rats. This study demonstrates that long-term inhalation exposures to environmentally relevant PM containing

  4. Dynamic behavioural changes in the Spontaneously Hyperactive Rat: 1. Control by place, timing, and reinforcement rate.

    PubMed

    Williams, Jonathan; Sagvolden, Geir; Taylor, Eric; Sagvolden, Terje

    2009-03-17

    Several existing theoretical models of Attention Deficit Hyperactivity Disorder (ADHD) predict that a high or low learning rate contributes to some cases of ADHD; and that this is controlled by the dopamine signal. The Spontaneously Hypertensive (Hyperactive) Rat has an abnormal Dopamine Transporter (DAT), which is likely to be hypofunctional, thereby increasing the dopamine concentration and the learning rate. We therefore test the prediction that the SHR learns too fast. Using a variable interval reinforcement schedule, we looked for increased responding within each interval, at around the durations of the last three intervals. At the time predicted by the previous interval, SHR responded significantly (10%) more than their baseline rate, and control WKY rats similarly less than their baseline. At the time predicted by the second (and third) previous intervals, there were minor trends (and no change) in the same direction. In summary, at the times predicted, SHR respond more than control rats. The effect size is insufficient to account for all the differences from control rats, such as their nearly threefold greater operant responding. At the times when SHR increase responding, WKY suppress it. This demonstrates similar learning to the SHR but the opposite response, probably due to anxiety about the bang accompanying reinforcer delivery: WKY are known to have a very negative response to stress. Interval schedules with randomised interval lengths have considerable potential for assessing multiple causes of behaviour, particularly those acting over short timecourses. Alterations in learning rate are not a sufficient explanation for either SHR or ADHD difference from controls.

  5. [MK-801 or DNQX reduces electroconvulsive shock-induced impairment of learning-memory and hyperphosphorylation of Tau in rats].

    PubMed

    Liu, Chao; Min, Su; Wei, Ke; Liu, Dong; Dong, Jun; Luo, Jie; Liu, Xiao-Bin

    2012-08-25

    This study explored the effect of the excitatory amino acid receptor antagonists on the impairment of learning-memory and the hyperphosphorylation of Tau protein induced by electroconvulsive shock (ECT) in depressed rats, in order to provide experimental evidence for the study on neuropsychological mechanisms improving learning and memory impairment and the clinical intervention treatment. The analysis of variance of factorial design set up two intervention factors which were the electroconvulsive shock (two level: no disposition; a course of ECT) and the excitatory amino acid receptor antagonists (three level: iv saline; iv NMDA receptor antagonist MK-801; iv AMPA receptor antagonist DNQX). Forty-eight adult Wistar-Kyoto (WKY) rats (an animal model for depressive behavior) were randomly divided into six experimental groups (n = 8 in each group): saline (iv 2 mL saline through the tail veins of WKY rats ); MK-801 (iv 2 mL 5 mg/kg MK-801 through the tail veins of WKY rats) ; DNQX (iv 2 mL 5 mg/kg DNQX through the tail veins of WKY rats ); saline + ECT (iv 2 mL saline through the tail veins of WKY rats and giving a course of ECT); MK-801 + ECT (iv 2 mL 5 mg/kg MK-801 through the tail veins of WKY rats and giving a course of ECT); DNQX + ECT (iv 2 mL 5 mg/kg DNQX through the tail veins of WKY rats and giving a course of ECT). The Morris water maze test started within 1 day after the finish of the course of ECT to evaluate learning and memory. The hippocampus was removed from rats within 1 day after the finish of Morris water maze test. The content of glutamate in the hippocampus of rats was detected by high performance liquid chromatography. The contents of Tau protein which included Tau5 (total Tau protein), p-PHF1(Ser396/404), p-AT8(Ser199/202) and p-12E8(Ser262) in the hippocampus of rats were detected by immunohistochemistry staining (SP) and Western blot. The results showed that ECT and the glutamate ionic receptor blockers (NMDA receptor antagonist MK-801 and

  6. Pharmacological characterization and autoradiographic localization of dihydropyridine-type calcium channels in the kidney of spontaneously hypertensive rats.

    PubMed

    Amenta, F; Liu, A; Sabbatini, M

    1995-12-01

    1. The pharmacological profile and the microanatomical localization of Ca2+ channels of the L-type were analysed in sections of the kidney of Wistar-Kyoto (WKY) rats and of spontaneously hypertensive rats (SHR) of different ages. 2. [3H]-Nicardipine was used as a ligand. It was bound to sections of rat kidney in a manner consistent with the labelling of Ca2+ channels of the L-type. The density of [3H]-nicardipine binding sites was similar in WKY rats of different ages and in SHR of 2 and 4 months, but was significantly increased in SHR of 6 months. 3. Light microscope autoradiography revealed the highest density of binding sites in the tubular portion of the nephron and to a lesser extent within smooth muscle of renal arteries and renal corpuscles. In SHR of 4 and 6 months the density of [3H]-nicardipine binding sites was increased within the epithelium of proximal tubules and of the loop of Henle and decreased in renal corpuscles in comparison with WKY rats or 2 month old SHR. 4. These results show that the density of Ca2+ channels of the L-type increases with the worsening of hypertension in SHR. The observation of a different sensitivity to hypertension of Ca2+ channels located in the various portions of the nephron indicates the usefulness of light microscope autoradiography for assessing hypertension-related changes of Ca2+ channels in the kidney.

  7. Effects of aging and hypertension on learning, memory, and activity in rats.

    PubMed

    Meneses, A; Castillo, C; Ibarra, M; Hong, E

    1996-08-01

    A comparison between behavioral alterations induced by hypertension and aging was made in spontaneously hypertensive (SHR) and Wistar-Kyoto rats (WKY) of different ages (3-24 months old), trained to perform autoshaping learning and activity tasks. Food-deprived rats received autoshaping training sessions during 6 days; the animals were retrained 1 month later. Two weeks after autoshaping training, the animals were evaluated in the spontaneous activity task during 2 consecutive days. The results show an age-related decrease in learning, memory, and spontaneous activity. Independently of the age group compared, WKY, though showing lower activity, learned and retrieved more than SHR. Accordingly, the reductions in learning and memory were correlated with both aging and hypertension. The combined influence of these two factors had synergistic detrimental effects on cognitive functions.

  8. Reduced L-carnitine transport in aortic endothelial cells from spontaneously hypertensive rats.

    PubMed

    Salsoso, Rocío; Guzmán-Gutiérrez, Enrique; Arroyo, Pablo; Salomón, Carlos; Zambrano, Sonia; Ruiz-Armenta, María Victoria; Blanca, Antonio Jesús; Pardo, Fabián; Leiva, Andrea; Mate, Alfonso; Sobrevia, Luis; Vázquez, Carmen María

    2014-01-01

    Impaired L-carnitine uptake correlates with higher blood pressure in adult men, and L-carnitine restores endothelial function in aortic rings from spontaneously hypertensive rat (SHR). Thus, endothelial dysfunction in hypertension could result from lower L-carnitine transport in this cell type. L-Carnitine transport is mainly mediated by novel organic cation transporters 1 (Octn1, Na(+)-independent) and 2 (Octn2, Na(+)-dependent); however, their kinetic properties and potential consequences in hypertension are unknown. We hypothesize that L-carnitine transport kinetic properties will be altered in aortic endothelium from spontaneously hypertensive rats (SHR). L-Carnitine transport was measured at different extracellular pH (pHo 5.5-8.5) in the absence or presence of sodium in rat aortic endothelial cells (RAECs) from non-hypertensive Wistar-Kyoto (WKY) rats and SHR. Octn1 and Octn2 mRNA relative expression was also determined. Dilation of endothelium-intact or denuded aortic rings in response to calcitonine gene related peptide (CGRP, 0.1-100 nmol/L) was measured (myography) in the absence or presence of L-carnitine. Total L-carnitine transport was lower in cells from SHR compared with WKY rats, an effect due to reduced Na(+)-dependent (Na(+) dep ) compared with Na(+)-independent (Na(+) indep ) transport components. Saturable L-carnitine transport kinetics show maximal velocity (V max), without changes in apparent K m for Na(+) indep transport in SHR compared with WKY rats. Total and Na(+) dep component of transport were increased, but Na(+) indep transport was reduced by extracellular alkalization in WKY rats. However, alkalization reduced total and Na(+) indep transport in cells from SHR. Octn2 mRNA was higher than Octn-1 mRNA expression in cells from both conditions. Dilation of artery rings in response to CGRP was reduced in vessels from SHR compared with WKY rats. CGRP effect was endothelium-dependent and restored by L-carnitine. All together these results

  9. Reduced L-Carnitine Transport in Aortic Endothelial Cells from Spontaneously Hypertensive Rats

    PubMed Central

    Salsoso, Rocío; Guzmán-Gutiérrez, Enrique; Arroyo, Pablo; Salomón, Carlos; Zambrano, Sonia; Ruiz-Armenta, María Victoria; Blanca, Antonio Jesús; Pardo, Fabián; Leiva, Andrea; Mate, Alfonso; Sobrevia, Luis; Vázquez, Carmen María

    2014-01-01

    Impaired L-carnitine uptake correlates with higher blood pressure in adult men, and L-carnitine restores endothelial function in aortic rings from spontaneously hypertensive rat (SHR). Thus, endothelial dysfunction in hypertension could result from lower L-carnitine transport in this cell type. L-Carnitine transport is mainly mediated by novel organic cation transporters 1 (Octn1, Na+-independent) and 2 (Octn2, Na+-dependent); however, their kinetic properties and potential consequences in hypertension are unknown. We hypothesize that L-carnitine transport kinetic properties will be altered in aortic endothelium from spontaneously hypertensive rats (SHR). L-Carnitine transport was measured at different extracellular pH (pHo 5.5–8.5) in the absence or presence of sodium in rat aortic endothelial cells (RAECs) from non-hypertensive Wistar-Kyoto (WKY) rats and SHR. Octn1 and Octn2 mRNA relative expression was also determined. Dilation of endothelium-intact or denuded aortic rings in response to calcitonine gene related peptide (CGRP, 0.1–100 nmol/L) was measured (myography) in the absence or presence of L-carnitine. Total L-carnitine transport was lower in cells from SHR compared with WKY rats, an effect due to reduced Na+-dependent (Na+dep) compared with Na+-independent (Na+indep) transport components. Saturable L-carnitine transport kinetics show maximal velocity (Vmax), without changes in apparent Km for Na+indep transport in SHR compared with WKY rats. Total and Na+dep component of transport were increased, but Na+indep transport was reduced by extracellular alkalization in WKY rats. However, alkalization reduced total and Na+indep transport in cells from SHR. Octn2 mRNA was higher than Octn-1 mRNA expression in cells from both conditions. Dilation of artery rings in response to CGRP was reduced in vessels from SHR compared with WKY rats. CGRP effect was endothelium-dependent and restored by L-carnitine. All together these results suggest that reduced L

  10. IMPACT OF ISOPRENALINE AND CAFFEINE ON DEVELOPMENT OF LEFT VENTRICULAR HYPERTROPHY AND RENAL HEMODYNAMIC IN WISTAR KYOTO RATS.

    PubMed

    Ahmad, Ashfaq; Sattar, Munavvar Z A; Rathore, Hassaan A; Khan, Safia Akhtar; Lazhari, Mohammed A; Hashmi, Fayaz; Abdullah, Nor A; Johns, Edward J

    2015-01-01

    Left ventricular hypertrophy (LVH) is a compensatory mechanism in response to an increased work load on the heart. This study investigated the impact of chronic isoprenaline and caffeine (I/C model) administration on cardiac geometry, systemic hemodynamic and physiological data in rats as LVH develops. LVH was induced by administering isoprenaline (5 mg/kg s.c. every 72 h) and caffeine (62 mg/L) in drinking water for 14 days to Wistar Kyoto (WKY) rats. Mean arterial pressure (MAP), systolic blood pressure (SBP), heart weight, LV weight, LV chamber diameter and thickness of myocardium were observed as LVH indicators. MAP was significantly higher (142 ± 13 vs. 119 ± 2 mmHg, respectively) while heart rate (HR) in LVH was lower (314 ± 9 vs. 264 ± 18 BPM) compared to control WKY. Heart weight, LV weight and kidney weight were 31%, 38% and 7%, respectively, greater in the LVH group as compared to the control WKY (all p < 0.05).The myocardium thickness was 101% greater while LV chamber diameter was 44% smaller in the LVH group as compared to the control WKY (p < 0.05). The superoxide dismutase (SOD), glutathione reductase (GSH) and total antioxidant capacity (T-AOC) levels were significantly reduced while malonodialdehyde (MDA) level increased in LVH as compared to control WKY (all p < 0.05). In conclusion, isoprenaline and caffeine (I/C) induces LVH and cardiac hypertrophy with increases in blood pressure, fluid excretion and reduced renal hemodynamics. Prooxidant mechanism of the body and arterial stiffness are dominant in this disease model. This model of LVH is easily generated and associated with low mortality.

  11. Effect of des-aspartate-angiotensin I on the actions of angiotensin II in the isolated renal and mesenteric vasculature of hypertensive and STZ-induced diabetic rats.

    PubMed

    Dharmani, M; Mustafa, M R; Achike, F I; Sim, M K

    2005-07-15

    The present study investigated the action of des-aspartate-angiotensin I (DAA-I) on the pressor action of angiotensin II in the renal and mesenteric vasculature of WKY, SHR and streptozotocin (STZ)-induced diabetic rats. Angiotensin II-induced a dose-dependent pressor response in the renal vasculature. Compared to the WKY, the pressor response was enhanced in the SHR and reduced in the STZ-induced diabetic rat. DAA-I attenuated the angiotensin II pressor action in renal vasculature of WKY and SHR. The attenuation was observed for DAA-I concentration as low as 10(-18) M and was more prominent in SHR. However, the ability of DAA-I to reduce angiotensin II response was lost in the STZ-induced diabetic kidney. Instead, enhancement of angiotensin II pressor response was seen at the lower doses of the octapeptide. The effect of DAA-I was not inhibited by PD123319, an AT2 receptor antagonist, and indomethacin, a cyclo-oxygenase inhibitor in both WKY and SHR, indicating that its action was not mediated by angiotensin AT2 receptor and prostaglandins. The pressor responses to angiotensin II in mesenteric vascular bed were also dose-dependent but smaller in magnitude compared to the renal vasculature. The responses were significantly smaller in SHR but no significant difference was observed between STZ-induced diabetic and WKY rat. Similarly, PD123319 and indomethacin had no effect on the action of DAA-I. The findings reiterate a regulatory role for DAA-I in vascular bed of the kidney and mesentery. By being active at circulating level, DAA-I subserves a physiological role. This function appears to be present in animals with diseased state of hypertension and diabetes. It is likely that DAA-I functions are modified to accommodate the ongoing vascular remodeling.

  12. Novel mechanism of intra‑renal angiotensin II-induced sodium/proton exchanger 3 expression by losartan in spontaneously hypertensive rats.

    PubMed

    Fan, Xiaoqin; Liu, Kaishan; Cui, Wei; Huang, Jiongmei; Wang, Weina; Gao, Yuan

    2014-11-01

    The present study aimed to investigate the molecular pharmacodynamic mechanisms of losartan used in the treatment of hypertension. A total of 12 spontaneously hypertensive rats (SHR) were divided randomly into an SHR group treated with saline and LOS group treated with losartan. Six Wistar‑kyoto rats (WKY) were enrolled as the WKY group with saline in the study. The LOS group received 30 mg/kg/day losartan by intragastric injection, while the SHR and WKY were fed the same volume of saline. The dosage was modulated according to the weekly weight. Changes in blood pressure were measured by the indirect tail cuff method. Angiotensin (Ang) II production in the plasma and renal tissue was measured by an immunoradiometric method. Na+/H+ exchanger (NHE)3 and serum and glucocorticoid‑inducible kinase (SGK)1 were assessed by quantitative polymerase chain reaction (qPCR) and western blot analysis. When compared with the WKY group, the blood pressure of the SHR and LOS groups were higher prior to treatment with losartan. Following two weeks, blood pressure was reduced and the trend continued to decrease over the following six weeks. The plasma and renal tissue levels of Ang II in the SHR and LOS groups were significantly higher than those in the WKY group. NHE3 and SGK1 were increased at the mRNA and protein level in the SHR group, and losartan reduced the expression of both of them. The results suggested that in hypertensive rats, the circular and tissue renin angiotensin systems were activated, and the increased Ang II stimulated the expression of NHE3 and SGK1, which was reduced by losartan. Therefore, the effects of losartan in hypertension may be associated with the Ang II‑SGK1‑NHE3 of intra‑renal tissue.

  13. Exaggerated sympathetic and cardiovascular responses to stimulation of the mesencephalic locomotor region in spontaneously hypertensive rats

    PubMed Central

    Liang, Nan; Mitchell, Jere H.; Smith, Scott A.

    2015-01-01

    The sympathetic and pressor responses to exercise are exaggerated in hypertension. However, the underlying mechanisms causing this abnormality remain to be fully elucidated. Central command, a neural drive originating in higher brain centers, is known to activate cardiovascular and locomotor control circuits concomitantly. As such, it is a viable candidate for the generation of the augmented vascular response to exercise in this disease. We hypothesized that augmentations in central command function contribute to the heightened cardiovascular response to exercise in hypertension. To test this hypothesis, changes in renal sympathetic nerve activity (RSNA) and mean arterial pressure (MAP) in response to electrical stimulation of mesencephalic locomotor region (MLR; 20–50 μA in 10-μA steps evoking fictive locomotion), a putative component of the central command pathway, were examined in decerebrate, paralyzed normotensive Wistar-Kyoto (WKY) and spontaneously hypertensive rats (SHR). Tibial nerve discharge during MLR stimulation significantly increased in an intensity-dependent manner in both WKY and SHR but was not different between groups. Stimulation of the MLR evoked significantly larger increases in RSNA and MAP with increasing stimulation intensity in both groups. Importantly, the increases in sympathetic and pressor responses to this fictive locomotion were significantly greater in SHR compared with WKY across all stimulation intensities (e.g., at 50 μA, ΔRSNA: WKY 153±31%, SHR 287±42%; ΔMAP: WKY 87±9 mmHg, SHR 139±7 mmHg). These findings provide the first evidence that central command may be a critical contributor to the exaggerated rise in sympathetic activity and blood pressure during exercise in hypertension. PMID:26545711

  14. Exaggerated sympathetic and cardiovascular responses to stimulation of the mesencephalic locomotor region in spontaneously hypertensive rats.

    PubMed

    Liang, Nan; Mitchell, Jere H; Smith, Scott A; Mizuno, Masaki

    2016-01-01

    The sympathetic and pressor responses to exercise are exaggerated in hypertension. However, the underlying mechanisms causing this abnormality remain to be fully elucidated. Central command, a neural drive originating in higher brain centers, is known to activate cardiovascular and locomotor control circuits concomitantly. As such, it is a viable candidate for the generation of the augmented vascular response to exercise in this disease. We hypothesized that augmentations in central command function contribute to the heightened cardiovascular response to exercise in hypertension. To test this hypothesis, changes in renal sympathetic nerve activity (RSNA) and mean arterial pressure (MAP) in response to electrical stimulation of mesencephalic locomotor region (MLR; 20-50 μA in 10-μA steps evoking fictive locomotion), a putative component of the central command pathway, were examined in decerebrate, paralyzed normotensive Wistar-Kyoto (WKY) and spontaneously hypertensive rats (SHR). Tibial nerve discharge during MLR stimulation significantly increased in an intensity-dependent manner in both WKY and SHR but was not different between groups. Stimulation of the MLR evoked significantly larger increases in RSNA and MAP with increasing stimulation intensity in both groups. Importantly, the increases in sympathetic and pressor responses to this fictive locomotion were significantly greater in SHR compared with WKY across all stimulation intensities (e.g., at 50 μA, ΔRSNA: WKY 153 ± 31%, SHR 287 ± 42%; ΔMAP: WKY 87 ± 9 mmHg, SHR 139 ± 7 mmHg). These findings provide the first evidence that central command may be a critical contributor to the exaggerated rise in sympathetic activity and blood pressure during exercise in hypertension.

  15. Porphyromonas gingivalis infection modifies oral microcirculation and aortic vascular function in the stroke-prone spontaneously hypertensive rat (SHRSP).

    PubMed

    Funaki, Seiko; Tokutomi, Fumiaki; Wada-Takahashi, Satoko; Yoshino, Fumihiko; Yoshida, Ayaka; Maehata, Yojiro; Miyamoto, Chihiro; Toyama, Toshizo; Sato, Takenori; Hamada, Nobushiro; Lee, Masaichi Chang-il; Takahashi, Shun-suke

    2016-03-01

    The functional modulation of vascular endothelial cells associated with stroke and periodontal disease has not yet been clarified. The objective of this study is to analyze the vascular endothelial function of periodontitis and stroke animal models. We examined endothelial function and gingival blood flow in oral microcirculation in vivo and measured the isometric tension in vitro of the aorta in animal models for lifestyle-related diseases, such as periodontitis and stroke. Gingival reactive hyperemia (GRH) was measured using laser Doppler flowmetry. Wistar Kyoto rats (WKY) were used as control animals; Porphyromonas gingivalis (P. gingivalis) infected WKY (WKY + Pg) as the periodontitis model; stroke-prone spontaneously hypertensive rat (SHRSP) as the stroke model; and a final group consisting of P. gingivalis infected SHRSP (SHRSP + Pg). Furthermore, for each group, the relaxation of descending aortic ring preparations was measured using a force transducer. The GRH was estimated by maximum response (peak), time taken for the maximum response to fall to one half (T1/2), and increased total amount of blood flow (mass). The relative change in T1/2 and mass increased in SHRSP + Pg compared to WKY. However, mass significantly increased in WKY (758.59 ± 88.21 ml/min/100 g s to 1755.55 ± 226.10 ml/min/100 g s) and SHRSP (1214.87 ± 141.61 ml/min/100 g s to 2674.32 ± 675.48 ml/min/100 g s) after treatment with acetylcholine. In addition, T1/2 and mass significantly increased in WKY + Pg (624.18 ± 96.36 ml/min/100 g s to 2629.90 ± 612.01 ml/min/100 g s) and SHRSP + Pg (1116.36 ± 206.24 ml/min/100 g s to 1952.76 ± 217.39 ml/min/100 g s) after treatment with nitroglycerin. Furthermore, the endothelium-dependent relaxation of ring preparations, evoked by acetylcholine, was attenuated in SHRSP compared with WKY, but not in SHRSP + Pg. This attenuation effect in SHRSP could be prevented by superoxide dismutase pretreatment. Our results suggest altered endothelial

  16. The effect of restraint stress on prepulse inhibition and on corticotropin-releasing factor (CRF) and CRF receptor gene expression in Wistar-Kyoto and Brown Norway rats

    PubMed Central

    Sutherland, Jane E.; Burian, Linda C.; Covault, Jonathan; Conti, Lisa H.

    2010-01-01

    Stress plays a role in many psychiatric disorders that are characterized by deficits in prepulse inhibition (PPI), a form of sensorimotor gating. Corticotropin-releasing factor (CRF) is one of the most important neurotransmitters involved in behavioral components of the stress response, and central infusion of CRF decreases PPI in rodents. We recently demonstrated that restraint stress decreases PPI and attenuates the increase in PPI caused by repeated testing. To broaden our investigation into how restraint affects PPI, we subjected Wistar-Kyoto (WKY) and Brown Norway (BN) rats to 10 consecutive days of 2-hour restraint, or to brief handling, prior to assessing PPI. We next examined the effects of 1 or 10 days of 2-hour restraint on plasma corticosterone levels in order to determine whether the endocrine response to stress parallels the behavioral effect of stress. Finally, we examined the effects of 1 or 10 days of 2-hour restraint on CRF and CRF receptor gene expression in the amygdala, hippocampus, frontal cortex, and hypothalamus in order to determine whether a temporal pattern of gene expression parallels the change in the behavioral response to stress. The major findings of the present study are that 1) restraint stress attenuates the increase in PPI caused by repeated testing in both WKY and BN rats, and BN rats are more sensitive to the effects of restraint on PPI than WKY rats, 2) restraint-induced increases in corticosterone levels mirror the effect of restraint on PPI in WKY rats but not in BN rats, 3) laterality effects on gene expression were observed for the amygdala, whereby restraint increases CRF gene expression in the left, but not right, amygdala, and 4) some restraint-induced changes in CRF and CRF receptor gene expression precede changes in PPI while other changes coincide with altered PPI in a rat strain- and brain region-dependent manner. PMID:20709096

  17. 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.

  18. Influence of acute progressive hypoxia on cardiovascular variability in conscious spontaneously hypertensive rats

    PubMed Central

    Sugimura, Mitsutaka; Hirose, Yohsuke; Hanamoto, Hiroshi; Okada, Kenji; Boku, Aiji; Morimoto, Yoshinari; Taki, Kunitaka; Niwa, Hitoshi

    2008-01-01

    The purpose of this study is to examine the influence of acute progressive hypoxia on cardiovascular variability and striatal dopamine (DA) levels in conscious, spontaneously hypertensive rats (SHR) and Wistar Kyoto rats (WKY). After preparation for measurement, the inspired oxygen concentration of rats was decreased to 10% within 5 min (descent stage), maintained at 10% for 10 min (fixed stage), and then elevated back to 20% over 5 min (recovery stage). The systolic blood pressure (SBP) and heart rate (HR) variability at each stage was calculated to evaluate the autonomic nervous system response using the wavelet method. Striatal DA during each stage was measured using in vivo microdialysis. We found that SHR showed a more profound hemodynamic response to progressive hypoxia as compared to WKY. Cardiac parasympathetic activity in SHR was significantly inhibited by acute progressive hypoxia during all stages, as shown by the decrease in the high frequency band of HR variability (HR-HF), along with transient increase in sympathetic activity during the early hypoxic phase. This decrease in the HR-HF continued even when SBP was elevated. Striatal DA levels showed the transient similar elevation in both groups. These findings suggest that acute progressive hypoxic stress in SHR inhibits cardiac parasympathetic activity through reduction of baroreceptor reflex sensitivity, with potentially severe deleterious effects on circulation, in particular on HR and circulatory control. Furthermore, it is thought that the influence of acute progressive hypoxia on striatal DA levels is similar in SHR and WKY. PMID:18599365

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

    PubMed

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

    2014-03-03

    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 (0.01mg/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 (1.0mA, 0.5s). 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.

  20. Contraction of arterial smooth muscle of normotensive and spontaneously hypertensive rats by manganese(III)tetrakis(1-methyl-4-pyridyl)porphyrin (MnTMPyP).

    PubMed

    Sekiguchi, Fumiko; Seo, Mikako; Sunano, Satoru

    2003-06-01

    Manganese(III)tetrakis(1-methyl-4-pyridyl)porphyrin (MnTMPyP), which has been known as a cell permeable superoxide dismutase mimetic, induced concentration-dependent contraction in rat carotid artery acting directly on smooth muscle. The contractile action was more prominent in the preparation from stroke-prone spontaneously hypertensive rats (SHRSP) compared with that from Wistar Kyoto rats (WKY). It was abolished by the removal of extracellular Ca(2+) or the application of verapamil. These results suggest that the MnTMPyP-induced contraction is brought about by Ca(2+) influx through voltage-dependent Ca(2+) channels (VDCC) and that the difference in VDCC is the cause of the difference in MnTMPyP action between preparations from WKY and SHRSP.

  1. Chronic stress induces structural alterations in splenic lymphoid tissue that are associated with changes in corticosterone levels in wistar-kyoto rats.

    PubMed

    Hernandez, María Eugenia; Martinez-Mota, Lucia; Salinas, Citlaltepetl; Marquez-Velasco, Ricardo; Hernandez-Chan, Nancy G; Morales-Montor, Jorge; Pérez-Tapia, Mayra; Streber, María L; Granados-Camacho, Ivonne; Becerril, Enrique; Javier, Baquera-Heredia; Pavón, Lenin

    2013-01-01

    Major depressive disorder patients present chronic stress and decreased immunity. The Wistar-Kyoto rat (WKY) is a strain in which the hypothalamic-pituitary-adrenal axis is overactivated. To determine whether chronic stress induces changes in corticosterone levels and splenic lymphoid tissue, 9-week-old male rats were subject to restraint stress (3 h daily), chemical stress (hydrocortisone treatment, 50 mg/Kg weight), mixed stress (restraint plus hydrocortisone), or control treatment (without stress) for 1, 4, and 7 weeks. The serum corticosterone levels by RIA and spleens morphology were analyzed. Corticosterone levels as did the structure, size of the follicles and morphology of the parenchyma (increase in red pulp) in the spleen, varied depending on time and type of stressor. These changes indicate that chronic stress alters the immune response in the spleen in WKY rats by inducing morphological changes, explaining in part the impaired immunity that develops in organisms that are exposed to chronic stress.

  2. Antihypertensive activities of a solid-state culture of Taiwanofungus camphoratus (Chang-chih) in spontaneously hypertensive rats.

    PubMed

    Liu, Der-Zen; Liang, Yu-Chih; Lin, Shyr-Yi; Lin, Yin-Shiou; Wu, Wen-Chun; Hou, Wen-Chi; Su, Ching-Hua

    2007-01-01

    Wild and solid-state cultures (SSC) of Taiwanofungus camphoratus (aka Antrodia camphorata and Chang-chih [CC]) were sequentially extracted with cold water, methanol, and hot water to get cold-water-soluble (CWS), methanol-soluble (MS), and hot-water-soluble (HWS) extracts, respectively. Only the MS extract exhibited angiotensin-converting enzyme (ACE) inhibitory activities. The antihypertensive effects of the MS extract (10 mg/kg BW) were measured in spontaneously hypertensive rats (SHR) and Wistar Kyoto (WKY) rats. MS extract of the SSC type was able to effectively lower the systolic blood pressure (SBP) and diastolic blood pressure (DBP) of SHR, but not of WKY rats, the results being significantly different from those for distilled water only (the blank). However, wild CC and its MS extract were not as effective as the SSC type in reducing SHR blood pressure and had no effect on WKY rats. SSC-type CC might be developed into a health food with the ability to regulate blood pressure.

  3. Immunohistochemical localization of angiotensin II receptor types 1 and 2 in the mesenteric artery from spontaneously hypertensive rats.

    PubMed

    Diniz, Carmen; Leal, Sandra; Logan, Karen; Rocha-Pereira, Carolina; Soares, Ana Sofia; Rocha, Eduardo; Gonçalves, Jorge; Fresco, Paula

    2007-08-01

    Angiotensin II plays a crucial role in the control of blood pressure, acting at AT1 or AT2 receptors, and can act as a potent vasoconstrictor of the peripheral vasculature inducing hypertrophy, hyperplasia, or both, in resistance arteries. The aim of the present study was to investigate whether the pattern of distribution of angiotensin AT1 and AT2 receptors on mesenteric artery sections differs in spontaneously hypertensive rats (SHR) versus their respective controls (Wistar-Kyoto [WKY] rats). Immunohistochemistry using anti-AT1 or anti-AT2 antibodies was performed on perfused-fixed/paraffin-embedded mesenteric arteries from SHR and WKY rats. 3,3'-Diaminobenzidine tetrahydrochloride (DAB; activated by hydrogen peroxide) staining revealed distinct AT1 and AT2 labeling of all artery layers (adventitia, media and intima) from WKY rats, whereas in SHR an abundant AT1 labeling was found in both intima and adventitia and a sparser labeling in the media. There was a vast reduction of AT2 labeling throughout all layers. These results suggest a crucial role for AT2 receptors in the pathogenesis of hypertension.

  4. Hyperglycemia accelerates apparent diffusion coefficient-defined lesion growth after focal cerebral ischemia in rats with and without features of metabolic syndrome.

    PubMed

    Tarr, David; Graham, Delyth; Roy, Lisa A; Holmes, William M; McCabe, Christopher; Mhairi Macrae, I; Muir, Keith W; Dewar, Deborah

    2013-10-01

    Poststroke hyperglycemia is associated with a poor outcome yet clinical management is inadequately informed. We sought to determine whether clinically relevant levels of hyperglycemia exert detrimental effects on the early evolution of focal ischemic brain damage, as determined by magnetic resonance imaging, in normal rats and in those modeling the 'metabolic syndrome'. Wistar Kyoto (WKY) or fructose-fed spontaneously hypertensive stroke-prone (ffSHRSP) rats were randomly allocated to groups for glucose or vehicle administration before permanent middle cerebral artery occlusion. Diffusion-weighted imaging was carried out over the first 4 hours after middle cerebral artery occlusion and lesion volume calculated from apparent diffusion coefficient maps. Infarct volume and immunostaining for markers of oxidative stress were measured in the fixed brain sections at 24 hours. Hyperglycemia rapidly exacerbated early ischemic damage in both WKY and ffSHRSP rats but increased infarct volume only in WKY rats. There was only limited evidence of oxidative stress in hyperglycemic animals. Acute hyperglycemia, at clinically relevant levels, exacerbates early ischemic damage in both normal and metabolic syndrome rats. Management of hyperglycemia may have greatest benefit when performed in the acute phase after stroke in the absence or presence of comorbidities.

  5. 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.

  6. StAR expression and the long-term aldosterone response to high-potassium diet in Wistar-Kyoto and spontaneously hypertensive rats.

    PubMed

    Peters, Barbara; Teubner, Philipp; Clausmeyer, Susanne; Puschner, Tanja; Maser-Gluth, Christiane; Wrede, Hans-Josef; Kränzlin, Bettina; Peters, Jörg

    2007-01-01

    ANG II and potassium are known to increase steroidogenic acute regulatory protein (StAR) levels. However, a corresponding increase in StAR mRNA levels has so far been observed only in response to ANG II. We therefore studied the regulation of adrenal StAR mRNA expression in the context of dietary potassium-stimulated aldosterone production. Wistar-Kyoto rats (WKY) and spontaneously hypertensive rats (SHR) were fed a diet containing either 1 or 4% KCl for 5 days. The high-potassium diet increased StAR mRNA levels within the zona glomerulosa in both strains, as demonstrated by in situ hybridization. However, aldosterone production increased in WKY but not in SHR (WKY: from 22.8 +/- 4.8 to 137 +/- 25 ng/100 ml, P < 0.001, vs. SHR: from 29 +/- 3.8 to 51 +/- 10.2 ng/100 ml, not significant). This increase was associated with an increase in Cyp11b2 mRNA levels in WKY (3-fold; P < 0.001) but not in SHR. In both strains, the 4% KCl diet was associated with increased plasma renin-independent aldosterone production, as indicated by the marked increase of the aldosterone-to-renin ratios (from 1.4 +/- 0.3 to 9 +/- 3 in WKY and from 3 +/- 1 to 14 +/- 5 in SHR; P < 0.002). We conclude that an increase of StAR mRNA levels within the outer cortex is involved in the long-term adrenal response to potassium. This increase alone is not sufficient to increase aldosterone production in the presence of normal Cyp11b2 mRNA levels.

  7. M-currents (Kv7.2-7.3/KCNQ2-KCNQ3) Are Responsible for Dysfunctional Autonomic Control in Hypertensive Rats

    PubMed Central

    Berg, Torill

    2016-01-01

    Autonomic dysfunctions play important roles in hypertension, heart failure and arrhythmia, often with a detrimental and fatal effect. The present study analyzed if these dysfunctions involved M-channels (members of the Kv7/KNCQ family) in spontaneously hypertensive rats (SHR). Cardiac output and heart rate (HR) were recorded by a flow probe on the ascending aorta in anesthetized SHR and normotensive rats (WKY), and blood pressure (BP) by a femoral artery catheter. Total peripheral vascular resistance (TPR) was calculated. XE-991 (Kv7.1-7.4-inhibitor) reduced resting HR in WKY but only after reserpine in SHR. XE-991 increased TPR and BP baseline in both strains. Retigabine (Kv7.2-7.5-opener) reduced HR, TPR and BP, also after reserpine. Depolarization induced by 3,4-diaminopyridine (3,4-DAP), a voltage-sensitive K+ channel (Kv) inhibitor, activated release of both acetylcholine and norepinephrine, thus activating an initial, cholinergic bradycardia in SHR, followed by sustained, norepinephrine-dependant tachycardia in both strains. XE-991 augmented the initial 3,4-DAP-induced bradycardia and eliminated the late tachycardia in SHR, but not in WKY. The increased bradycardia was eliminated by hexamethonium and methoctramine (M2muscarinic receptor antagonist) but not reserpine. Retigabine eliminated the increased bradycardia observed in reserpinized SHR. XE-991 also increased 3,4-DAP-stimulated catecholamine release, but not after hexamethonium or reserpine. Conclusions: M-currents hampered parasympathetic ganglion excitation and, through that, vagal control of HR, in SHR but not WKY. M-currents also opposed catecholamine release in SHR but not in WKY. M-currents represented a vasodilatory component in resting TPR-control, with no strain-related difference detected. Excessive M-currents may represent the underlying cause of autonomic dysfunctions in hypertension. PMID:27965589

  8. Fullerenols and glucosamine fullerenes reduce infarct volume and cerebral inflammation after ischemic stroke in normotensive and hypertensive rats.

    PubMed

    Fluri, Felix; Grünstein, Dan; Cam, Ertugrul; Ungethuem, Udo; Hatz, Florian; Schäfer, Juliane; Samnick, Samuel; Israel, Ina; Kleinschnitz, Christoph; Orts-Gil, Guillermo; Moch, Holger; Zeis, Thomas; Schaeren-Wiemers, Nicole; Seeberger, Peter

    2015-03-01

    Cerebral inflammation plays a crucial role in the pathophysiology of ischemic stroke and is involved in all stages of the ischemic cascade. Fullerene derivatives, such as fullerenol (OH-F) are radical scavengers acting as neuroprotective agents while glucosamine (GlcN) attenuates cerebral inflammation after stroke. We created novel glucosamine-fullerene conjugates (GlcN-F) to combine their protective effects and compared them to OH-F regarding stroke-induced cerebral inflammation and cellular damage. Fullerene derivatives or vehicle was administered intravenously in normotensive Wistar-Kyoto (WKY) rats and spontaneously hypertensive rats (SHR) immediately after transient middle cerebral artery occlusion (tMCAO). Infarct size was determined at day 5 and neurological outcome at days 1 and 5 after tMCAO. CD68- and NeuN-staining were performed to determine immunoreactivity and neuronal survival respectively. Cytokine and toll like receptor 4 (TLR-4) expression was assessed using quantitative real-time PCR. Magnetic resonance imaging revealed a significant reduction of infarct volume in both, WKY and SHR that were treated with fullerene derivatives. Treated rats showed an amelioration of neurological symptoms as both OH-F and GlcN-F prevented neuronal loss in the perilesional area. Cerebral immunoreactivity was reduced in treated WKY and SHR. Expression of IL-1β and TLR-4 was attenuated in OH-F-treated WKY rats. In conclusion, OH-F and GlcN-F lead to a reduction of cellular damage and inflammation after stroke, rendering these compounds attractive therapeutics for stroke.

  9. 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

  10. Effects of age and hypertension on α1-adrenoceptors in the major source arteries of the rat bladder and penis.

    PubMed

    Yono, Makoto; Tanaka, Takanori; Tsuji, Shigeki; Irie, Shin; Sakata, Yukikuni; Otani, Masayuki; Yoshida, Masaki; Latifpour, Jamshid

    2011-11-16

    α(1)-Adrenoceptors regulate blood pressure, regional vascular resistance and tissue blood flow. As aging and hypertension may impact pelvic arterial blood flow resulting in bladder and penile dysfunction, we investigated effects of age and hypertension on α(1)-adrenoceptors in the major source arteries of the rat bladder and penis. Using radioligand receptor binding, real-time reverse transcription-polymerase chain reaction (RT-PCR) and fluorescent microsphere infusion techniques, we compared 3 and 22-month-old male Fischer rats, and male normotensive Wistar-Kyoto (WKY) rats and spontaneously hypertensive rats (SHRs). Twenty-two-month-old rats and SHRs had significantly higher total α(1)-adrenoceptor density in the internal iliac artery and lower blood flow to the bladder and penis than 3-month-old and WKY rats, respectively. RT-PCR data showed an age and hypertension related increase in the expression of α(1B)-adrenoceptor mRNA in the internal iliac, vesical and internal pudendal arteries and a switch from α(1A) predominance in 3-month-old and WKY rats to α(1B)>α(1A) in 22-month-old rats and SHRs. Our data indicate the presence of age and hypertension related alterations in vascular α(1)-adrenoceptor subtype distribution and in blood flow to the rat bladder and penis. These findings suggest that pharmacological blockade of the vascular α(1B)-adrenoceptor, which could increase pelvic blood flow, may contribute to the improvement of bladder and penile dysfunctions in animal models for aging and hypertension.

  11. Applicability of a "speed" congenic strategy to dissect blood pressure quantitative trait loci on rat chromosome 2.

    PubMed

    Jeffs, B; Negrin, C D; Graham, D; Clark, J S; Anderson, N H; Gauguier, D; Dominiczak, A F

    2000-01-01

    The identification of any quantitative trait locus (QTL) via a genome scan is only the first step toward the ultimate goal of gene identification. The next step is the production of congenic strains by which the existence of a QTL may be verified and the implicated chromosomal region be reduced to a size applicable to positional cloning of the causal gene. We used a speed congenic breeding protocol previously verified in mice for 2 blood pressure QTLs on rat chromosome 2. Four congenic strains were produced through introgression of various segments of chromosome 2 from Wistar-Kyoto rats from Glasgow colonies [WKY((Gla)) rats] into the recipient stroke-prone spontaneously hypertensive rats from Glasgow colonies [SHRSP((Gla))], and vice versa. The number of backcross generations required for each strain to achieve complete homozygosity at 83 background genetic markers in a "best" male varied between 3 and 4. Transfer of the region of rat chromosome 2 containing both QTLs from WKY((Gla)) into an SHRSP((Gla)) genetic background lowered both baseline and salt-loaded systolic blood pressure by approximately 20 and approximately 40 mm Hg in male congenic rats compared with the SHRSP parental strain (F=53.4, P<0.005; F=28.0, P< 0.0005, respectively). In contrast, control animals for stowaway heterozygosity presented no deviation from the blood pressure values recorded for the SHRSP((Gla)), indicating that if such heterozygosity exists, its effect on blood pressure is negligible. A reciprocal strategy in which 1 or both QTLs on rat chromosome 2 were transferred from SHRSP((Gla)) into a WKY((Gla)) genetic background resulted in statistically significant but smaller blood pressure increases for 1 of these QTLs. These results confirm the existence of blood pressure QTLs on rat chromosome 2 and demonstrate the applicability of a speed congenic strategy in the rat and emphasize the important role of the genetic background.

  12. 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

  13. Cellular distribution of calcium current is unaltered during compensated hypertrophy in the spontaneously hypertensive rat.

    PubMed

    Fowler, Mark R; Orchard, Clive H; Harrison, Simon M

    2007-01-01

    Changes in cellular calcium (Ca(2+)) handling are thought to underlie the altered contraction that occurs during cardiac hypertrophy and failure. Recent work has highlighted the importance of t-tubules in the control of intracellular Ca(2+). The present study was performed to investigate whether changes in the distribution of I (Ca) between the surface and t-tubule membranes might contribute to the altered Ca(2+) handling observed during compensated hypertrophy in the spontaneously hypertensive rat (SHR). Experiments were performed on ventricular myocytes isolated from 5-month-old SHR and normotensive Wistar-Kyoto (WKY) control rats. Osmotic shock using formamide was used to disrupt the t-tubular system and the whole-cell patch clamp technique used to monitor I (Ca) in the presence and absence of t-tubules. Membrane capacitance and I (Ca) were greater in control SHR than WKY myocytes; following detubulation, cell capacitance and I (Ca) both decreased and were no longer significantly different in the two cell types. The density of I (Ca) was not significantly different in control SHR and WKY cells or in detubulated myocytes from the two species. These data suggest that the distribution of I (Ca) is unchanged in SHR myocytes compared to WKY controls; I (Ca) density in the t-tubules was 1.2-fold greater than in the sarcolemma in both strains. These data also imply that the increase in surface area in SHR myocytes is due principally to an increase in t-tubular area, which is accompanied by an approximately equivalent increase in I (Ca), so that the density of I (Ca) at the cell surface and in the t-tubules remains the same. These changes would be expected to retain cell function and synchronicity of Ca(2+) release in the SHR at this stage of compensated hypertrophy.

  14. 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.

  15. 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

  16. 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

  17. Quantitative Indexes of Leukocytes in Spontaneously Hypertensive Rats During Various Periods of Arterial Hypertension Development.

    PubMed

    Aliev, O I; Anishchenko, A M; Sidekhmenova, A V; Shamanaev, A Yu; Fedorova, E P; Plotnikov, M B

    2015-10-01

    SHR rats were examined in the period before arterial hypertension development (5th week), during the increase in BP (6th-10th weeks), and under conditions of constantly elevated BP (11th-12th weeks). The total number of leukocytes did not differ in SHR and normotensive WKY rats. However, the relative number of lymphocytes and monocytes was shown to differ in various periods of arterial hypertension development. Our results suggest that white blood cells (primarily lymphocytes) are involved in the development of arterial hypertension.

  18. 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.

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

    PubMed Central

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

    2015-01-01

    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 (SKCa) 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 SKCa 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 SKCa and Na-K ATPase, a phenomenon that is also observed in mesenteric arteries of older normotensive rats. PMID:26171229

  20. Pharmacokinetics of a new proton pump inhibitor, YJA-20379-8, after intravenous and oral administration to spontaneously hypertensive rats and DOCA-salt-induced hypertensive rats.

    PubMed

    Kim, H J; Han, K S; Kim, Y G; Chung, Y K; Chang, M S; Lee, M G

    2000-11-01

    The purpose of this study was to investigate the causes for the differences observed in the pharmacokinetics of YJA-20379-8 in 16-week-old spontaneously hypertensive rats (SHRs). To see if the hereditary characteristics of SHRs was the cause, 20 mg/kg of the drug was intravenously infused over 15 min and 50 mg/kg of the drug was orally administered to 6-week-old SHRs and 16-week-old SHRs and their age-matched control Kyoto-Wistar (KW) rats. Also to see if the hypertensive status itself was the cause, the same doses were administered to 16-week-old deoxycorticosterone acetate (DOCA) salt-induced hypertensive rats (DOCA-salt rats) and their age-matched control Sprague-Dawley rats. The areas under the plasma concentration-time curve from time zero to time infinity (for intravenous study) and to the last sampling time in plasma (for oral study) were significantly smaller after both intravenous and oral administration, and the total body clearances of the drug were significantly faster after intravenous administration to 6-week-old SHRs, 16-week-old SHRs, and 16-week-old DOCA-salt rats than those in their respective age-matched control rats. The above pharmacokinetic parameter changes in 16-week-old SHRs were due to both hereditary characteristic of SHRs and the hypertensive status itself.

  1. 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.

  2. Gene expression in the adrenal glands of three spontaneously hypertensive rat substrains.

    PubMed

    Ashenagar, Mohammad S; Tabuchi, Masaki; Kinoshita, Kosho; Ooshima, Kana; Niwa, Atsuko; Watanabe, Yuko; Yoshida, Momoko; Shimada, Kazunori; Yasunaga, Teruo; Yamanishi, Hiromichi; Higashino, Hideaki

    2010-01-01

    We examined gene expression profiles in rat adrenal glands using genome-wide microarray technology. Gene expression levels were determined in four rat strains, including one normotensive strain [Wistar-Kyoto (WKY)] and three substrains derived from WKY rats: spontaneously hypertensive rats (SHR), stroke-prone SHR (SHRSP) and malignant SHRSP (M-SHRSP). This study represents the first attempt at using microarrays to compare gene expression profiles in SHR, SHRSP and M-SHRSP adrenal glands, employing WKY as controls. Expression measurements were made in these four rat strains at 6 and 9 weeks of age; 6 weeks of age covers the pre-hypertensive period in SHR and SHRSP, and 9 weeks of age is the period of rapidly rising blood pressure (BP). Since the aim of this study was to identify candidate genes involved in the genesis of hypertension in the SHR substrains, we identified genes that were consistently different in their expression, isolating 87 up-regulated genes showing a more than 4-fold increase and 128 down-regulated genes showing a less than 1/4-fold decrease in at least two different experiments. We classified all these up- or down-regulated genes by their expression profiles, and searched for candidate genes. At 6 weeks of age, several BP-regulating genes including sparc/osteonectin (Spock2), kynureninase (Kynu), regulator of G-protein signaling 2 (Rgs2) and gap junction protein α1 (Gja1) were identified as up-regulated, and urotensin 2 (Uts2), cytoplasmic epoxide hydrolase 2 (Ephx2), apelin (Apln), insulin-like growth factor 1 receptor (Igf1r) and angiotensin II receptor-associated protein (Agtrap) were identified as down-regulated. The Kynu and Ephx2 genes have previously been reported by other groups to be responsible for hypertension in SHR; however, our present approach identified at least seven new candidate genes.

  3. 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

  4. Effects of a protocol of ischemic postconditioning and/or captopril in hearts of normotensive and hypertensive rats.

    PubMed

    Penna, Claudia; Tullio, Francesca; Moro, Francesca; Folino, Anna; Merlino, Annalisa; Pagliaro, Pasquale

    2010-03-01

    Brief periods (a few seconds) of cyclic coronary occlusions applied early in reperfusion induce a cardioprotection against infarct size, called postconditioning (PostC) in which B(2)-bradykinin receptors play a pivotal role. Since angiotensin-converting enzyme (ACE) inhibitors reduce degradation of kinins, we studied the effects of PostC on infarct size and postischemic myocardial dysfunction in both normotensive (WKY) and spontaneously hypertensive rats (SHR) acutely or chronically treated with the ACE inhibitor Captopril. Isolated hearts from SHR and WKY rats were subjected to the following protocols: (a) ischemia for 30- and 120-min reperfusion (I/R); (b) I/R + PostC protocol (5-cycles 10-s I/R); (c) pretreatment with Captopril for 4-weeks before to subject the hearts to I/R with or without PostC maneuvers. Some SHR hearts were treated with Captopril during the 20- or 40-min early reperfusion with or without PostC maneuvers. Cardiac function was assessed in vivo with echocardiography. Left ventricular pressure and infarct size were measured ex vivo. Chronic Captopril significantly reduced left ventricular hypertrophy in SHR, and reduced infarct size in both WKY and SHR hearts. PostC maneuvers significantly reduced infarct size in WKY, but not in SHR hearts. Yet, PostC slightly improved postischemic systolic function in untreated SHR. Captopril given in reperfusion was unable to limit I/R injury in SHR hearts. Data show that PostC protection against infarct size is blunted in SHR and that PostC is unable to add its protective effect to those of chronic Captopril, which per se reduces cardiac hypertrophy and heart susceptibility to I/R insult.

  5. Effects of dihydropyridines on tension and calcium-45 influx in isolated mesenteric resistance vessels from spontaneously hypertensive and normotensive rats

    SciTech Connect

    Cauvin, C.; Hwang, O.; Yamamoto, M.; van Breemen, C.

    1987-01-30

    Contractile tension responses to norepinephrine and depolarizing potassium (80 mM K+), as well as calcium-45 influx stimulated by these agents, were studied in isolated mesenteric resistance vessels (each 100 microM internal diameter) from spontaneously hypertensive rats (SHRs) and from normotensive Wistar Kyoto rats (WKYs). Inhibitory effects of 2 dihydropyridine Ca++ antagonists, PN 200-110 (isradipine) and nisoldipine, on these parameters were also determined. Contractile responses to 80 mM K+ were inhibited by both Ca++ antagonists with the same potency and efficacy in SHR compared with WKY vessels (PN 200-110 IC50 = 2.8 +/- 1.3 X 10(-8) M in SHRs and 2.5 +/- 1.5 X 10(-8) M in WKYs; nisoldipine IC50 = 1.1 +/- 0.4 X 10(-8) M in SHRs and 1.2 +/- 0.9 X 10(-8) M in WKYs). However, contractile responses to norepinephrine (10(-4) M) were inhibited less potently by nisoldipine in SHR vessels (IC50 = 2.2 +/- 0.3 X 10(-9) M) compared with WKY vessels (IC50 = 1.6 +/- 0.6 X 10(-10) M). Similarly, PN 200-110 tended to be less (but not significantly less) potent in SHR vessels (IC50 = 3.3 +/- 1.8 X 10(-8) M) than in WKY vessels (IC50 = 3.4 +/- 0.9 X 10(-9) M); its efficacy was significantly depressed in the SHR vessels (by approximately 20%). When norepinephrine-stimulated calcium-45 influx was determined in the presence of these Ca++ antagonists, a similar profile emerged with respect to a comparison of SHR and WKY vessels. These results support a previously hypothesized alteration in receptor-activated Ca++ influx pathways in SHR mesenteric resistance vessels.

  6. Age-related changes in body fluid volumes in young spontaneously hypertensive rats

    SciTech Connect

    Von Dreele, M.M. )

    1988-11-01

    The authors have measured total body water (TBW, by dessiccation), extracellular fluid volume (ECF, Na{sub 2}{sup 35}SO{sub 4} space), and plasma volume (PV, radioiodinated serum albumin space) in 5-sec-butyl-5-ethyl-2-thiobarbituric acid and sodium salt (Inactin)-anesthetized spontaneously hypertensive (SHR) and Wistar-Kyoto (WKY) rats aged 12-60 days. Interstitial fluid volume (ISF) was calculated as ECF minus PV. Changes in TBW, ECF, and ISF were largely a function of age in both strains, which is typical of developing mammals. Further analysis revealed that although these volumes were significantly larger in SHR before 25 days of age, after 30 days no difference existed between the strains. Before 25 days of age, when SHR's TBW was expanded, no weight difference was seen between the strains. However, once TBW was normalized (after 30 days), WKY was significantly heavier than SHR. The ISF volume was preferentially enlarged in SHR, although PV was also periodically greater. ISF normalized at the time when blood pressure becomes significantly higher in SHR, when plasma aldosterone falls to WKY values in SHR and when renal function is approaching adult levels. Thus the return of ECF (ISF) to normal values may be a result of decreased aldosterone-dependent volume retention or to diuresis induced by increasing blood pressure in an animal whose renal function is close to maturity.

  7. Maternal separation increases GABA(A) receptor-mediated modulation of norepinephrine release in the hippocampus of a rat model of ADHD, the spontaneously hypertensive rat.

    PubMed

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

    2013-02-25

    Experiencing early life stress increases the risk of developing a psychiatric disorder later in life, possibly by altering neural networks, such as the locus-coeruleus norepinephrine (LC-NE) system. Whether early life stress affects the LC-NE system directly, or whether the effects are via changes in glutamate and GABA modulation of the LC-NE system, is unclear. Early life stress has been shown to alter glutamate and GABA transmission, and in particular, to alter GABA(A) receptor expression. The LC-NE system has been implicated in attention-deficit/hyperactivity disorder (ADHD), amongst other disorders, and is over-responsive to glutamate stimulation in a validated rat model of ADHD, the spontaneously hypertensive rat (SHR). It is plausible that the LC-NE system, or glutamate and GABA modulation thereof, in an individual already genetically predisposed to develop ADHD, or in SHR, may respond in a unique way to early life stress. To investigate this we applied a mild developmental stressor, maternal separation, onto SHR, and onto their control strain, Wistar-Kyoto rats (WKY), from post-natal day (P)2-14. On P50-52, in early adulthood, we assayed glutamate and potassium stimulated release of radio-actively labelled NE ((3)[H]NE) from hippocampal slices using an in vitro superfusion technique, in the presence or absence of a GABA(A) receptor antagonist, bicuculline. Our results show that maternal separation altered GABA(A) receptor-mediated modulation of NE release in the hippocampus of the two strains in opposite directions, increasing it in SHR and decreasing it in WKY. Our findings indicate that effects of early life stress are highly dependent on genetic predisposition, since opposite changes in GABA(A) receptor-mediated modulation of NE release were observed in the rat model of ADHD, SHR, and their control strain, WKY.

  8. L-carnitine and propionyl-L-carnitine improve endothelial dysfunction in spontaneously hypertensive rats: different participation of NO and COX-products.

    PubMed

    Bueno, Rosario; Alvarez de Sotomayor, Maria; Perez-Guerrero, Concepción; Gomez-Amores, Lucia; Vazquez, Carmen M; Herrera, M Dolores

    2005-09-09

    L-carnitine and propionyl-L-carnitine are supplements to therapy in cardiovascular pathologies. Their effect on endothelial dysfunction in hypertension was studied after treatment with either 200 mg/kg of L-carnitine or propionyl-L-carnitine during 8 weeks of spontaneously hypertensive rats (SHR) and normotensive Wistar Kyoto rats (WKY). Endothelial function was assessed in aortic rings by carbachol-induced relaxation (CCh 10(-8) to 10(-4) M) and factors involved were characterized in the presence of the inhibitors: L-NAME, indomethacin, the TXA2/PGH2 Tp receptor antagonist ICI-192,605 and the thromboxane synthetase inhibitor-Tp receptor antagonist, Ro-68,070. The effect on phenylephrine-induced contractions was also observed. To identify the nature of vasoactive COX-derived products, enzyme-immunoassay of incubation media was assessed. Involvement of reactive oxygen species was evaluated by incubating with superoxide dismutase and catalase. Nitric oxide production was evaluated by serum concentration of NO2+NO3.Treatment with both compounds improved endothelial function of rings from SHR without blood pressure change. Propionyl-L-carnitine increased NO participation in WKY and SHR. L-carnitine reduced endothelium-dependent responses to CCh in WKY due to an increase of TXA2 production. In both SHR and WKY, L-carnitine enhanced concentration of PGI2 and increased participation of NO. Results in the presence of SOD plus catalase show that it might be related to antioxidant properties of L-carnitine and propionyl-L-carnitine. Comparison between the effect of both compounds shows that both may reduce reactive oxygen species and increase NO participation in endothelium-dependent relaxations in SHR. However, only L-carnitine was able to increase the release of the vasodilator PGI2 and even enhanced TXA2 production in normotensive rats.

  9. Enhanced noradrenergic transmission in the spontaneously hypertensive rat anococcygeus muscle

    PubMed Central

    Jiménez-Altayó, Francesc; Giraldo, Jesús; McGrath, John C; Vila, Elisabet

    2003-01-01

    There is a long-known hyper-responsiveness of vascular adrenergic transmission in the spontaneously hypertensive rat (SHR) that is uncovered specifically in the presence of cocaine and attributed to blockade of the neuronal monoamine transporter. We have now used the rat anococcygeus muscle to investigate whether this phenomenon is generic to sympathetic transmission to smooth muscle rather than a purely vascular phenomenon. We sought the origin of the effect by successively blocking the buffering effects of the neuronal monoamine transporter, prejunctional α2-adrenoceptors and NO from nitrergic nerves with desipramine (0.1 μM), rauwolscine (0.01 μM) and L-NG-nitro-arginine (100 μM). In the presence of desipramine, contractile responses to electrical field stimulation but not to noradrenaline (1 nM–100 μM) were greater in SHR than in Wistar–Kyoto (WKY). Neither inhibition of prejunctional α2-adrenoceptors nor the blockade of neuronal nitric oxide synthase (nNOS) accounted for the differential enhancement of response in SHR. The enhanced effectiveness of motor neurotransmission in SHR becomes most apparent when all known major buffering mechanisms are removed. When nitrergic responses were isolated pharmacologically (phentolamine 1 μM and guanethidine 30 μM; tone raised with carbachol 50 μM), they were not different between SHR and WKY. Western blots showed that both nNOS and tyrosine hydroxylase are expressed to a similar extent in anococcygeus muscle from SHR and WKY, suggesting similar adrenergic and nitrergic innervations in the two strains. This suggests that enhanced motor transmission is due to increased transmitter release per varicosity rather than there being normal transmission from a greater number of sites. We conclude that there is a generic enhancement of sympathetic transmission in SHR rather than this being a vascular phenomenon. PMID:14504140

  10. PAN-811 inhibits oxidative stress-induced cell death of human Alzheimer's disease-derived and age-matched olfactory neuroepithelial cells via suppression of intracellular reactive oxygen species.

    PubMed

    Nelson, Valery M; Dancik, Chantée M; Pan, Weiying; Jiang, Zhi-Gang; Lebowitz, Michael S; Ghanbari, Hossein A

    2009-01-01

    Oxidative stress plays a significant role in neurotoxicity associated with a variety of neurodegenerative diseases including Alzheimer's disease (AD). Increased oxidative stress has been shown to be a prominent and early feature of vulnerable neurons in AD. Olfactory neuroepithelial cells are affected at an early stage. Exposure to oxidative stress induces the accumulation of intracellular reactive oxygen species (ROS), which in turn causes cell damage in the form of protein, lipid, and DNA oxidations. Elevated ROS levels are also associated with increased deposition of amyloid-beta and formation of senile plaques, a hallmark of the AD brain. If enhanced ROS exceeds the basal level of cellular protective mechanisms, oxidative damage and cell death will result. Therefore, substances that can reduce oxidative stress are sought as potential drug candidates for treatment or preventative therapy of neurodegenerative diseases such as AD. PAN-811, also known as 3-aminopyridine-2-carboxaldehyde thiosemicarbazone or Triapine, is a small lipophilic compound that is currently being investigated in several Phase II clinical trials for cancer therapy due to its inhibition of ribonucleotide reductase activity. Here we show PAN-811 to be effective in preventing or reducing ROS accumulation and the resulting oxidative damages in both AD-derived and age-matched olfactory neuroepithelial cells.

  11. 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

  12. Differential mechanisms of ang (1-7)-mediated vasodepressor effect in adult and aged candesartan-treated rats.

    PubMed

    Bosnyak, S; Widdop, R E; Denton, K M; Jones, E S

    2012-01-01

    Angiotensin (1-7) (Ang (1-7)) causes vasodilator effects in Wistar-Kyoto (WKY) rats and spontaneously hypertensive rats (SHRs) via angiotensin type 2 receptors (AT(2)R). However, the role of vascular AT(2)R in aging is not known. Therefore, we examined the effect of aging on Ang (1-7)-mediated vasodepressor effects and vascular angiotensin receptor localization in aging. Blood pressure was measured in conscious adult (~17 weeks) and aged (~19 months) normotensive rats that received drug combinations in a randomised fashion over a 4-day protocol: (i) Ang (1-7) alone, (ii) AT(1)R antagonist, candesartan, alone, (iii) Ang (1-7) and candesartan, or (iv) Ang-(1-7), candesartan, and the AT(2)R antagonist, PD123319. In a separate group of animals, the specific MasR antagonist, A779, was administered in place of PD123319. Receptor localisation was also assessed in aortic sections from adult and aged WKY rats by immunofluorescence. Ang (1-7) reduced blood pressure (~15 mmHg) in adult normotensive rats although this effect was dependant on the background dose of candesartan. This depressor effect was reversed by AT(2)R blockade. In aged rats, the depressor effect of Ang (1-7) was evident but was now inhibited by either AT(2)R blockade or MasR blockade. At the same time, AT(2)R, MasR, and ACE2 immunoreactivity was markedly elevated in aortic sections from aged animals. These results indicate that the Ang (1-7)-mediated depressor effect was preserved in aged animals. Whereas Ang (1-7) effects were mediated exclusively via stimulation of AT(2)R in adult WKY, with aging the vasodepressor effect of Ang (1-7) involved both AT(2)R and MasR.

  13. Diesel Exhaust Worsens Cardiac Conduction Instability in Dobutamine-Challenged Wistar-Kyoto and Spontaneously Hypertensive Rats.

    PubMed

    Hazari, Mehdi S; Lancaster, Jarrett L; Starobin, Joseph M; Farraj, Aimen K; Cascio, Wayne E

    2017-04-01

    Short-term exposure to air pollution, particularly from vehicular sources, increases the risk of acute clinical cardiovascular events. However, cardiotoxicity is not always clearly discernible under ambient conditions; therefore, more subtle measures of cardiac dysfunction are necessary to elucidate the latent effects of exposure. Determine the effect of whole diesel exhaust (DE) exposure on reserve of refractoriness (RoR), an intrinsic electrophysiological measure of the heart's minimum level of refractoriness relative to development of electrical conduction instability, in rats undergoing exercise-like stress. Wistar-Kyoto (WKY) and spontaneously hypertensive (SH) rats implanted with radiotelemeters to continuously collect electrocardiogram (ECG) and heart rate were exposed to 150 µg/m(3) of DE and challenged with dobutamine 24 h later to mimic exercise-induced increases of the heart rate. The Chernyak-Starobin-Cohen (CSC) model was then applied to the ECG-derived QT and RR intervals collected during progressive increases in heart rate to calculate RoR for each rat. Filtered air-exposed WKY and SH rats did not have any decrease in RoR, which indicates increased risk of cardiac conduction instability; however, DE caused a significant decrease in both strains. Yet, the decrease in RoR in SH rats was eight times steeper when compared to WKY rats indicating greater cardiac conduction instability in the hypertensive strain. These data indicate that after exposure to DE, risk of cardiac instability increases during increasing stress, particularly in the presence of underlying cardiovascular disease. Furthermore, the CSC model, which was previously shown to reveal cardiac risk in humans, can be applied to rodent toxicology studies.

  14. Characterization of the macrophage transcriptome in glomerulonephritis-susceptible and -resistant rat strains.

    PubMed

    Maratou, K; Behmoaras, J; Fewings, C; Srivastava, P; D'Souza, Z; Smith, J; Game, L; Cook, T; Aitman, T

    2011-03-01

    Crescentic glomerulonephritis (CRGN) is a major cause of rapidly progressive renal failure for which the underlying genetic basis is unknown. Wistar-Kyoto (WKY) rats show marked susceptibility to CRGN, whereas Lewis rats are resistant. Glomerular injury and crescent formation are macrophage dependent and mainly explained by seven quantitative trait loci (Crgn1-7). Here, we used microarray analysis in basal and lipopolysaccharide (LPS)-stimulated macrophages to identify genes that reside on pathways predisposing WKY rats to CRGN. We detected 97 novel positional candidates for the uncharacterized Crgn3-7. We identified 10 additional secondary effector genes with profound differences in expression between the two strains (>5-fold change, <1% false discovery rate) for basal and LPS-stimulated macrophages. Moreover, we identified eight genes with differentially expressed alternatively spliced isoforms, by using an in-depth analysis at the probe level that allowed us to discard false positives owing to polymorphisms between the two rat strains. Pathway analysis identified several common linked pathways, enriched for differentially expressed genes, which affect macrophage activation. In summary, our results identify distinct macrophage transcriptome profiles between two rat strains that differ in susceptibility to glomerulonephritis, provide novel positional candidates for Crgn3-7 and define groups of genes that play a significant role in differential regulation of macrophage activity.

  15. 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

  16. Long-term effects of benidipine on cerebral vasoreactivity in hypertensive rats.

    PubMed

    Kitayama, Jiro; Kitazono, Takanari; Ooboshi, Hiroaki; Takada, Junichi; Fujishima, Masatoshi; Ibayashi, Setsuro

    2002-03-08

    We tested the hypothesis that long-term application of a Ca2+ channel blocker would ameliorate the functional and morphological deterioration of the cerebral arteries during hypertension. Male spontaneously hypertensive rats (SHR) were fed a standard rat chow, containing a low (3 mg/kg/day) or high dose (6 mg/kg/day) of benidipine, a Ca2+ channel blocker, for 2 months. Using a cranial window, we examined responses of the basilar artery to acetylcholine, sodium nitroprusside, (-)-(3S,4R)-4-(N-acetyl-N-hydroxyamino)-6-cyano-3,4-dihydro-2,2-dimethyl-2H-1-benzopyran-3-ol (Y-26763; an opener of ATP-sensitive K+ channels), and (R)-(+)-trans-N-(4-pyridyl)-4-(1-aminoethyl)-cyclohexanecarboxamide (Y-27632; an inhibitor of Rho-associated kinase). Mean arterial pressure of the control group was 193+/-5 mm Hg (mean+/-S.E.M.), while that of the low-dose benidipine group was 183+/-5 mm Hg and that of the high-dose group was 159+/-4 mm Hg. Dilator responses of the basilar artery to acetylcholine and Y-26763 were impaired in SHR compared with those of normotensive Wistar-Kyoto (WKY) rats and treatment with benidipine enhanced the vasodilator responses to acetylcholine and Y-26763 in SHR. Y-27632-induced dilatation of the basilar artery was enhanced in SHR compared to that in WKY rats and the vasodilatation was reduced by benidipine in SHR. Sodium nitroprusside caused similar dilatation of the basilar artery, in both WKY rats and the SHR control group, and benidipine did not affect nitroprusside-induced dilatation of the artery in SHR. The wall of the basilar artery was significantly thicker in SHR than in WKY rats and benidipine treatment reduced the wall thickness of the artery in SHR. These findings suggest that chronic treatment with a Ca2+ channel blocker may enhance the dilator capacity and reduce contractility of the basilar artery during hypertension. Benidipine may also ameliorate the morphological changes of the basilar artery in hypertension.

  17. Increase of cardiac M2-muscarinic receptor gene expression in type-1 but not in type-2 diabetic rats.

    PubMed

    Lee, Liang-Ming; Chang, Cheng Kuei; Cheng, Kai-Chun; Kou, Dai-Huang; Liu, I-Min; Cheng, Juei-Tang

    2008-08-22

    Changes of cardiac M2-muscarinic receptor (M2-mAChR) gene expression was investigated in type-1 like diabetic rats induced by intravenous injection of streptozotocin (STZ) and type-2 like diabetic rats induced by fed with fructose-rich chow. Systolic blood pressure (SBP) in STZ-diabetic rats was significantly lower than that in age-matched non-diabetic rats, while the SBP in type-2 like diabetic rats was higher than in non-diabetic rats. Also, the mRNA or protein level of cardiac M2-mAChR in STZ-diabetic rats was markedly higher than non-diabetic rats, but it was not observed in type-2 like diabetic rats as compared to age-matched non-diabetic rats. Arecaidine propargyl ester (APE), the agonist of M2-mAChR, produced a marked reduction of heart rate in STZ-diabetic rats but made less influence on heart rate in fructose-fed rats or non-diabetic rats. The results suggest that cardiac M2-mAChR gene expression is raised in type-1 like diabetic rats but not in type-2 like diabetic rats, this difference mainly due to hyperglycemia, for the production of hypotension in diabetic disorders.

  18. Spontaneously hypertensive, Wistar Kyoto and Sprague-Dawley rats differ in their use of place and response strategies in the water radial arm maze.

    PubMed

    Clements, K M; Saunders, A J; Robertson, B-A; Wainwright, P E

    2007-02-01

    This study further characterises the use of mnemonic systems in the spontaneously hypertensive rat (SHR), which is frequently used as a rodent model of attention deficit hyperactivity disorder. The objective of this study was to assess the preference of male SHR, Wistar-Kyoto (WKY) and Sprague-Dawley (SD) rats for a place or response strategy when trained on an ambiguous T-maze task, and also to examine whether all strains acquired information about both strategies during ambiguous training, regardless of their preferred strategy. In the first experiment, SHR and WKY showed a preference for a response strategy on the ambiguous T-maze task; in contrast, SD displayed a preference for a place strategy. In the second experiment, all strains demonstrated that they learned information about both the response and place strategies during ambiguous training. However, on a conditioned place preference test SHR did not display as strong a preference for the place arm as WKY and SD. This finding supports previous research in a conditioned cue preference test, in which SHR did not display a preference for the cue associated with the platform. These observations that the strains differ with respect to behavioural strategy in a learning task suggest that they differ in the underlying neural circuitry that serves goal-directed behaviour, and are consistent with SHR having deficits associated with the nucleus accumbens.

  19. Antihypertensive effects of androgens in conscious, spontaneously hypertensive rats.

    PubMed

    Perusquía, Mercedes; Herrera, Nieves; Ferrer, Mercedes; Stallone, John N

    2017-03-01

    Androgens are vasoactive steroids that induce acute vasodilation in a number of isolated vascular beds from different species, but the effects of these hormones on systemic blood pressure (BP) have been studied little. Although it has been reported that androgens exert systemic hypotensive effects through peripheral vasodilation in normotensive rats, there have not been any reports of systemic hypotensive effects of androgens in animals with hypertension. This study was designed to evaluate the acute effects of testosterone (TES) and its 5-reduced metabolites on systemic BP in hypertensive rats and to test the hypothesis that hypotestosteronemia may be involved in the pathogenesis of hypertension. Chronic, indwelling catheters were implanted in carotid artery and jugular vein of 18-21-week-old male spontaneously hypertensive rats (SHR) and normotensive-control Wistar-Kyoto (WKY) rats, for BP recording and drug administration, respectively. Bolus injections of TES, 5α- or 5β-dihydrotestosterone (5α- and 5β-DHT), were administrated cumulatively to conscious rats at doses of 0.1-100μmolkg(-1)min(-1). 5β-DHT was also administrated during the pressor effect of Bay K 8644, an L-type voltage-operated Ca(2+) channel (L-VOCC) agonist. In separate experiments, BP of orchidectomized normotensive male WKY and Wistar rats, with or without androgen-replacement therapy, was evaluated weekly for 10 weeks by tail-cuff plethysmography. TES and its metabolites reduced BP in a dose-dependent manner, while heart rate was reduced with some androgens at the highest doses. The hypotensive effects of androgens were markedly greater in SHR, with a rank order potency of: 5β-DHT>TES>5α-DHT. 5β-DHT, the most potent antihypertensive androgen, abolished the pressor response to Bay K 8644 in SHR. TES deprivation by orchidectomy increased BP in normotensive WKY and Wistar rats, but this hypertension was prevented by TES replacement therapy. BP responses to androgens are androgen structure

  20. 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.

  1. 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.

  2. Neuronal nitric oxide synthase expression is lower in areas of the nucleus tractus solitarius excited by skeletal muscle reflexes in hypertensive rats

    PubMed Central

    Mizuno, Masaki; Downey, Ryan M.; Squiers, John J.; Squiers, Kathryn E.; Smith, Scott A.

    2013-01-01

    The functions of the skeletal muscle exercise pressor reflex (EPR) and its mechanically sensitive component are augmented in hypertension producing exaggerated increases in blood pressure during exercise. Afferent information from the EPR is processed in the nucleus tractus solitarius (NTS). Within the NT, nitric oxide (NO), produced via l-arginine oxidation by neuronal nitric oxide synthase (nNOS), buffers the pressor response to EPR activation. Therefore, EPR overactivity may manifest as a decrease in NO production due to reductions in nNOS. We hypothesized that nNOS protein expression is lower in the NTS of spontaneously hypertensive (SHR) compared with normotensive Wistar-Kyoto (WKY) rats. Further, we examined whether nNOS is expressed with FOS, a marker of neuronal excitation induced by EPR activation. The EPR and mechanoreflex were intermittently activated for 1 h via hindlimb static contraction or stretch, respectively. These maneuvers produced significantly greater pressor responses in SHR during the first 25 min of stimulation. Within the NTS, nNOS expression was lower from −14.9 to −13.4 bregma in SHR compared with WKY. For example, at −14.5 bregma the number of NTS nNOS-positive cells in SHR (13 ± 1) was significantly less than WKY (23 ± 2). However, the number of FOS-positive cells after muscle contraction in this area was not different (WKY = 82 ± 18; SHR = 75 ± 8). In both groups, FOS-expressing neurons were located within the same areas of the NTS as neurons containing nNOS. These findings demonstrate that nNOS protein expression is lower within NTS areas excited by skeletal muscle reflexes in hypertensive rats. PMID:23564306

  3. Disturbance of vasodilation via protease-activated receptor 2 in SHRSP.Z-Lepr fa/IzmDmcr rats with metabolic syndrome.

    PubMed

    Kagota, Satomi; Maruyama, Kana; Wakuda, Hirokazu; McGuire, John J; Yoshikawa, Noriko; Nakamura, Kazuki; Shinozuka, Kazumasa

    2014-10-01

    Protease-activated receptor-2 (PAR2) activation causes vascular inflammation and vasodilation, but its role in metabolic syndrome (MetS) remains uncertain. Therefore, we examined whether the PAR2-induced vasodilation of SHRSP.Z-Lepr(fa)/IzmDmcr rats (SHRSP.ZF) is impaired and if so, whether administering telmisartan is protective. PAR2-activating peptide, 2-furoyl-LIGRLO-amide (2fly), relaxed the isolated superior and first-order branches of mesenteric arteries (MAs) from Wistar-Kyoto rats (WKY) and SHRSP.ZF. Superior-MA relaxation by 2fly was less in SHRSP.ZF than in WKY. Relaxation of first-order MAs by 2fly was the same in SHRSP.ZF and WKY. NO synthase inhibitor partially reduced 2fly-induced relaxation of superior and first-order MAs in SHRSP.ZF and WKY; inhibition of relaxation was proportionately larger in SHRSP.ZF. In SHRSP.ZF, nitroprusside-induced relaxation and the expression of soluble guanylyl cyclase decreased. In SHRSP.ZF, telmisartan reversed these abnormalities, and decreased blood pressure and serum levels of thiobarbituric acid reactive substances, an index of oxidative stress. Vasodilation via PAR2 activation was preserved in small-caliber MAs, in contrast to large-caliber MAs, even when MetS reduced NO-dependent relaxation mechanisms. NO and non-NO relaxing factor(s) contributed to PAR2-mediated relaxation in MAs, and the balance between factors may be altered to preserve vasodilation in MetS. Telmisartan prevented vascular dysfunction in MetS by protecting arteries against oxidative stress.

  4. The NO stimulator, Catestatin, improves the Frank-Starling response in normotensive and hypertensive rat hearts.

    PubMed

    Angelone, T; Quintieri, A M; Pasqua, T; Filice, E; Cantafio, P; Scavello, F; Rocca, C; Mahata, S K; Gattuso, A; Cerra, M C

    2015-08-01

    The myocardial response to mechanical stretch (Frank-Starling law) is an important physiological cardiac determinant. Modulated by many endogenous substances, it is impaired in the presence of cardiovascular pathologies and during senescence. Catestatin (CST:hCgA352-372), a 21-amino-acid derivate of Chromogranin A (CgA), displays hypotensive/vasodilatory properties and counteracts excessive systemic and/or intra-cardiac excitatory stimuli (e.g., catecholamines and endothelin-1). CST, produced also by the myocardium, affects the heart by modulating inotropy, lusitropy and the coronary tone through a Nitric Oxide (NO)-dependent mechanism. This study evaluated the putative influence elicited by CST on the Frank-Starling response of normotensive Wistar-Kyoto (WKY) and hypertensive (SHR) hearts by using isolated and Langendorff perfused cardiac preparations. Functional changes were evaluated on aged (18-month-old) WKY rats and SHR which mimic human chronic heart failure (HF). Comparison to WKY rats, SHR showed a reduced Frank-Starling response. In both rat strains, CST administration improved myocardial mechanical response to increased end-diastolic pressures. This effect was mediated by EE/IP3K/NOS/NO/cGMP/PKG, as revealed by specific inhibitors. CST-dependent positive Frank-Starling response is paralleled by an increment in protein S-Nitrosylation. Our data suggested CST as a NO-dependent physiological modulator of the stretch-induced intrinsic regulation of the heart. This may be of particular importance in the aged hypertrophic heart, whose function is impaired because of a reduced systolic performance accompanied by delayed relaxation and increased diastolic stiffness.

  5. Pulmonary transcriptional response to ozone in healthy and cardiovascular compromised rat models.

    PubMed

    Ward, William O; Kodavanti, Urmila P

    2015-01-01

    The genetic cardiovascular disease (CVD) and associated metabolic impairments can influence the lung injury from inhaled pollutants. We hypothesized that comparative assessment of global pulmonary expression profile of healthy and CVD-prone rat models will provide mechanistic insights into susceptibility differences to ozone. The lung expression profiles of healthy Wistar Kyoto (WKY) and CVD-compromised spontaneously hypertensive (SH), stroke-prone SH (SHSP), obese SH heart failure (SHHF) and obese, atherosclerosis-prone JCR rats were analyzed using Affymetrix platform immediately after 4-h air or 1 ppm ozone exposure. At baseline, the JCR exhibited the largest difference in the number of genes among all strains when compared with WKY. Interestingly, the number of genes affected by ozone was inversely correlated with genes different at baseline relative to WKY. A cluster of NFkB target genes involved in cell-adhesion, antioxidant response, inflammation and apoptosis was induced in all strains, albeit at different levels (JCR < WKY < SHHF < SH < SHSP). The lung metabolic syndrome gene cluster indicated expressions in opposite directions for SHHF and JCR suggesting different mechanisms for common disease phenotype and perhaps obesity-independent contribution to exacerbated lung disease. The differences in expression of adrenergic receptors and ion-channel genes suggested distinct mechanisms by which ozone might induce protein leakage in CVD models, especially SHHF and JCR. Thus, the pulmonary response to ozone in CVD strains was likely linked to the defining gene expression profiles. Differential transcriptional patterns between healthy and CVD rat strains at baseline, and after ozone suggests that lung inflammation and injury might be influenced by multiple biological pathways affecting inflammation gene signatures.

  6. Interleukin-1β Accelerates the Onset of Stroke in Stroke-Prone Spontaneously Hypertensive Rats

    PubMed Central

    Chiba, Tsuyoshi; Itoh, Tatsuki; Tabuchi, Masaki; Nakazawa, Toru; Satou, Takao

    2012-01-01

    High blood levels of inflammatory biomarkers and immune cells in stroke lesions have been recognized as results of stroke. However, recent studies have suggested that inflammation occurs prior to stroke onset. In this study, we aimed to clarify the role of inflammation in stroke onset among stroke-prone spontaneously hypertensive rats (SHRSP). At 4 weeks of age (before stroke onset), the plasma level of IL-1β was significantly higher in SHRSP (153.0 ± 49.7 pg/ml) than in Wistar Kyoto rats (WKY) (7.7 ± 3.4 pg/ml, P < 0.001 versus SHRSP) or spontaneously hypertensive rats (SHR) (28.0 ± 9.1 pg/ml, P < 0.001 versus SHRSP) (n = 6 per strain). Stimulated IL-1β signal was also observed in cerebrovascular endothelial cells of SHRSP. Gene expressions of IL-1β, IL-1 receptors, caspase-1, and downstream genes (MCP-1 and ICAM-1), which associated with immune cell recruitment, were significantly greater in SHRSP than in WKY or SHR, coincident with greater NFκB protein levels in SHRSP compared to WKY or SHR. In addition, continuous administration of IL-1β (2 μg/day) using an osmotic pump slightly increased the incidence of stroke in SHR (P = 0.046) and significantly accelerated the onset of stroke in SHRSP (P = 0.006) compared to each control (n = 10 per group). These results suggest that a stimulated IL-1β signal might be a cause of stroke onset when concomitant with severe hypertension. PMID:23326018

  7. Age-related changes in growth hormone-immunoreactive cells in the anterior pituitary gland of Jcl: Wistar-TgN (ARGHGEN) 1Nts rats (Mini rats).

    PubMed

    Matsumoto, Yoshiki; Tsukamoto, Yasuhiro; Miki, Takanori; Ogawa, Kazushige; Lee, Kyoung-Youl; Yokoyama, Toshifumi; Satriotomo, Irawan; Li, Hong-Peng; Gu, He; Wang, Zhi-Yu; Karasawa, Shigeru; Ueda, Susumu; Sasaki, Fumihiko; Takeuchi, Yoshiki

    2006-12-01

    Rats of the Jcl: Wistar-TgN (ARGHGEN) 1Nts strain (Mini rats) are transgenic animals carrying an antisense RNA transgene for rat growth hormone (GH); they show poor somatic growth and a low blood GH level compared to age-matched wild-type Wistar (non-Mini) rats. The purpose of the present study was to investigate age-related changes in growth hormone-immunoreactive (GH-IR) cells in the anterior pituitary gland (AP) of Mini rats at four, six, and eight weeks of age. The body weight and size of the GH-IR cells of Mini rats was significantly lower than that of non-Mini rats at six and eight weeks of age; however, this difference was not observed at four weeks of age. The AP volume and the number of GH-IR cells in Mini rats were significantly smaller than those of the age-matched non-Mini rats at the three ages. These results suggest that the abnormal development of GH-IR cells in the AP induced by the GH antisense RNA transgene is responsible for the poor somatic growth and the low blood GH levels in Mini rats.

  8. 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

  9. Aortic depressor nerve stimulation does not impede dynamic characteristics of the carotid sinus baroreflex in normotensive or spontaneously hypertensive rats.

    PubMed

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

    2017-03-08

    Recent clinical trials in patients with drug-resistant hypertension indicate that electrical activation of the carotid sinus baroreflex (baroreflex activation therapy) can reduce arterial pressure (AP) for more than a year. To examine whether the electrical stimulation from one baroreflex system impedes normal short-term AP regulation via another unstimulated baroreflex system, we electrically stimulated the left aortic depressor nerve (ADN) while estimating the dynamic characteristics of the carotid sinus baroreflex in anesthetized normotensive Wistar-Kyoto (WKY, n=8) rats and spontaneously hypertensive rats (SHR, n=7). Isolated carotid sinus regions were perturbed for 20 min using a Gaussian white noise signal with a mean of 120 mmHg for WKY and 160 mmHg for SHR. Tonic ADN stimulation (2 Hz, 10 V, 0.1-ms pulse width) decreased mean sympathetic nerve activity (73.4±14.0 vs. 51.6±11.3 arbitrary units in WKY, P = 0.012; and 248.7±33.9 vs. 181.1±16.6 arbitrary units in SHR, P = 0.018) and mean AP (90.8±6.6 vs. 81.2±5.4 mmHg in WKY, P=0.004; and 128.6±9.8 vs. 114.7±10.3 mmHg in SHR, P = 0.009). The slope of dynamic gain in the neural arc transfer function from carotid sinus pressure to sympathetic nerve activity was not different between trials with and without the ADN stimulation (12.55±0.93 vs. 13.03±1.28 dB/decade in WKY, P = 0.542; and 17.37±1.01 vs. 17.47±1.64 dB/decade in SHR, P = 0.946). These results indicate that the tonic ADN stimulation does not significantly modify the dynamic characteristics of the carotid sinus baroreflex.

  10. Renin and angiotensinogen gene expression in maturing rat kidney

    SciTech Connect

    Gomez, R.A.; Lynch, K.R.; Chevalier, R.L.; Wilfong, N.; Everett, A.; Carey, R.M.; Peach, M.J. )

    1988-04-01

    To determine whether angiotensinogen (A{sub o}) and renin are synthesized by the immature kidney and to assess the changes in intrarenal reinin distribution that occur with maturation, the kidneys from 24 newborn and 12 adult Wistar-Kyoto (WKY) and spontaneously hypertensive rats (SHR) were processed for renin immunocytochemistry using a highly specific anti-rat renin antibody. Kidney renin and A{sub o} relative mRNA levels (mRNA/total RNA) were detected by Northern and dot blot techniques, using full-length rat renin and A{sub o} cDNAs. Renal renin concentration (RRC) was measured by radioimmunoassay of angiotensin I (ANG I) and expressed as ng ANG I{center dot}h{sup {minus}1}{center dot}mg protein{sup {minus}1} in the incubation media. RRC was higher in newborn than in adult SHR (979 {+-} 164 vs. 206 {+-} 47) and WKY. In the newborn kidneys of both rat strains, renin was distributed throughout the entire length of the afferent arterioles and interlobular arteries, whereas in the adult kidneys renin was confined to the classical juxtaglomerular position. With maturation, there was a decrease in the proportion of immunoreactive juxtaglomerular apparatuses and arterial segments that contained renin. Kidney renin mRNA levels were 7.9-fold higher in the newborn than in the adult animals. A{sub o} mRNA was detected in the newborn and adult kidneys of both rat strains. This study demonstrates conclusively that both renin and A{sub o} genes are expressed in the newborn kidney, providing evidence for a local renin-angiotensin system that is subjected to developmental changes.

  11. 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

  12. In vivo brain microdialysis studies on the striatal dopamine and serotonin release in zitter mutant rats.

    PubMed

    Yoshimoto, Kanji; Nishimura, Akira; Hattori, Hiroyuki; Joyce, Jeffery N; Yoshida, Toshihide; Hioki, Chizuko; Kogure, Akinori; Ueda, Shuichi

    2006-07-01

    In the present study, using in vivo brain microdialysis, we investigated the basal extracellular dopamine (DA) and serotonin (5-HT) release in the caudal striatum (cSTR) of young (4-6 months old) and aged (10-12 months old) zitter mutant rats. The basal extracellular levels of DA release in both young and aged zitter rats were significantly lower than that of age-matched Sprague-Dawley (SD) rats, whereas only aged zitter rats showed a significant difference in the basal 5-HT release. Dopaminergic neurons were more vulnerable than serotonergic neurons in the cSTR of zitter mutant rats during aging. Perfusion of 60 mM potassium (K+) enhanced the extracellular levels of cSTR DA in the young zitter rats and the extracellular levels of both DA and 5-HT in the cSTR of the aged zitter rats. The firing rate of K+-stimulated monoamine release in the cSTR was significantly higher in the zitter rats than in the age-matched SD rats. These findings suggest that there are innate quantitative differences in the releasable pool and the availability of monoamines in the cSTR of zitter mutant rats.

  13. Rearing in an enriched environment attenuated hyperactivity and inattention in the Spontaneously Hypertensive Rats, an animal model of Attention-Deficit Hyperactivity Disorder.

    PubMed

    Botanas, Chrislean Jun; Lee, Hyelim; de la Peña, June Bryan; Dela Peña, Irene Joy; Woo, Taeseon; Kim, Hee Jin; Han, Doug Hyun; Kim, Bung-Nyun; Cheong, Jae Hoon

    2016-03-01

    Attention-deficit hyperactivity disorder (ADHD) is a prevalent neurodevelopmental disorder, characterized by symptoms of hyperactivity, inattention, and impulsivity. It is commonly treated with psychostimulants that typically begins during childhood and lasts for an extended period of time. However, there are concerns regarding the consequences of chronic psychostimulant treatment; thus, there is a growing search for an alternative management for ADHD. One non-pharmacological management that is gaining much interest is environmental enrichment. Here, we investigated the effects of rearing in an enriched environment (EE) on the expression of ADHD-like symptoms in the Spontaneously Hypertensive Rats (SHRs), an animal model of ADHD. SHRs were reared in EE or standard environment (SE) from post-natal day (PND) 21 until PND 49. Thereafter, behavioral tests that measure hyperactivity (open field test [OFT]), inattention (Y-maze task), and impulsivity (delay discounting task) were conducted. Additionally, electroencephalography (EEG) was employed to assess the effects of EE on rat's brain activity. Wistar-Kyoto (WKY) rats, the normotensive counterpart of the SHRs, were used to determine whether the effects of EE were specific to a particular genetic background. EE improved the performance of the SHRs and WKY rats in the OFT and Y-maze task, but not the delay discounting task. Interestingly, EE induced significant EEG changes in WKY rats, but not in the SHRs. These findings show that rearing environment may play a role in the expression of ADHD-like symptoms in the SHRs and that EE may be considered as a putative complementary approach in managing ADHD symptoms.

  14. A novel function of microRNA let-7d in regulation of galectin-3 expression in attention deficit hyperactivity disorder rat brain.

    PubMed

    Wu, Lihui; Zhao, Qianlei; Zhu, Xuchao; Peng, Min; Jia, Chenyou; Wu, Wei; Zheng, Jing; Wu, Xing Zhong

    2010-11-01

    In this study we investigated the locomotor activity and non-selective attention in spontaneously hypertensive rats (SHR) with control Wistar-Kyoto (WKY) rats, which were employed as an attention deficit hyperactivity disorder (ADHD) model. In open-field test and làt maze, SHR rats were found to be much more spontaneously active than WKY rats. As compared with WKY rats, a lower level of galectin-3 was observed in SHR brain prefrontal cortex (PFC), which was the major affected brain area of ADHD. Through miRNA microarray screening, rno-let-7d was noted to be solely upregulated in SHR PFC. Interestingly, rno-let-7d had a binding site at galectin-3 mRNA and was shown to regulate galectin-3 3' untranslated region (UTR) directly. Mutation of galectin-3 3'UTR by one nucleotide of the seed sequence prevented rno-let-7d regulation of the 3' UTR completely. Although rno-let-7d did not directly regulate tyrosine hydroxylase (TH) 3'UTR, the level of galectin-3 was important for cAMP response element binding protein, the major transcript factor for TH gene. Either overexpression or downexpression of galectin-3 could result in modulation of TH expression in both PC12H and PC12L cells. In conclusion, our data suggested a novel function of rno-let-7d in regulation of galectin-3 and in ADHD development. Rno-let-7d, which is increased in the PFC of SHR brain, negatively regulated galectin-3, which is coupled with TH expression regulation.

  15. Interaction of perivascular adipose tissue and sympathetic nerves in arteries from normotensive and hypertensive rats.

    PubMed

    Török, J; Zemančíková, A; Kocianová, Z

    2016-10-24

    The inhibitory action of perivascular adipose tissue (PVAT) in modulation of arterial contraction has been recently recognized and contrasted with the prohypertensive effect of obesity in humans. In this study we demonstrated that PVAT might have opposing effect on sympatho-adrenergic contractions in different rat conduit arteries. In superior mesenteric artery isolated from normotensive Wistar-Kyoto rats (WKY), PVAT exhibited inhibitory influence on the contractions to exogenous noradrenaline as well as to endogenous noradrenaline released from arterial sympathetic nerves during transmural electrical stimulation or after application of tyramine. In contrast, the abdominal aorta with intact PVAT responded with larger contractions to transmural electrical stimulation and tyramine when compared to the aorta after removing PVAT; the responses to noradrenaline were similar in both. This indicates that PVAT may contain additional sources of endogenous noradrenaline which could be responsible for the main difference in the modulatory effect of PVAT on adrenergic contractions between abdominal aortas and superior mesenteric arteries. In spontaneously hypertensive rats (SHR), the anticontractile effect of PVAT in mesenteric arteries was reduced, and the removal of PVAT completely eliminated the difference in the dose-response curves to exogenous noradrenaline between SHR and WKY. These results suggest that in mesenteric artery isolated from SHR, the impaired anticontractile influence of PVAT might significantly contribute to its increased sensitivity to adrenergic stimuli.

  16. Hypertension and impairment of endothelium-dependent relaxation of arteries from spontaneously hypertensive and L-NAME-treated Wistar rats.

    PubMed

    Sekiguchi, F; Miyake, Y; Hirakawa, A; Nakahira, T; Yamaoka, M; Shimamura, K; Yamamoto, K; Sunano, S

    2001-04-01

    Effects of chronic treatment of normotensive Wistar rats with N(omega)-nitro-L-arginine methyl ester (L-NAME) on blood pressure and on endothelium-dependent relaxation of the aorta, carotid and iliac arteries were studied. The endothelium-dependent relaxation was compared in arteries from normotensive Wistar Kyoto rats (WKY) and genetically hypertensive rats (stroke-prone spontaneously hypertensive rats, SHRSP). Chronic treatment of normotensive Wistar rats with L-NAME caused an elevation of blood pressure. The elevated blood pressure at 15 weeks of age was significantly higher in these animals than that of untreated Wistar rats, but lower than that of SHRSP. Endothelium-dependent relaxation of the arteries induced by acetylcholine (ACh) was almost abolished by chronic treatment with L-NAME. The remaining small relaxation in arteries from L-NAME-treated rats was completely inhibited by application of L-NAME (10(-4) M). In such preparations, higher concentrations of ACh induced a contraction, which was abolished by removal of the endothelium or by an application of indomethacin (10(-5) M). Endothelium-independent relaxation induced by sodium nitroprusside was similar between preparations from untreated and L-NAME-treated Wistar rats. Endothelium-dependent relaxation was significantly impaired in preparations from SHRSP, when compared with that in those from WKY. However, the impairment was less prominent in preparations from SHRSP than in those from L-NAME-treated rats. These results suggest that the impairment of endothelium-dependent relaxation in the arteries from L-NAME-treated rats is not due to the elevated blood pressure resulting from the chronic treatment, and that impairment of NO synthesis by the endothelium does not play a major role in the initiation of hypertension in SHRSP.

  17. Decreased α4β2 nicotinic receptor number in the absence of mRNA changes suggest post-transcriptional regulation in the spontaneously hypertensive rat model of ADHD

    PubMed Central

    Wigestrand, MB; Mineur, YS; Heath, CJ; Fonnum, F; Picciotto, MR; Walaas, SI

    2011-01-01

    The spontaneously hypertensive rat (SHR) is widely used as a model of attention-deficit/hyperactivity disorder (ADHD). Deficits in central nicotinic receptors (nAChRs) have previously been observed in SHRs, which is interesting since epidemiological studies have identified an association between smoking and ADHD symptoms in humans. Here we examine whether nAChR deficits in SHRs compared to Wistar Kyoto rat (WKY) controls are nAChR subtype-specific and whether these deficits correlate with changes at the level of mRNA transcription in specific brain regions. Levels of binding sites (Bmax) and dissociation constants (Kd) for nAChRs were determined from saturation curves of high-affinity [3H]epibatidine- and [3H]MLA binding to membranes from cortex, striatum, hippocampus and cerebellum. In additional brain regions, nAChRs were examined by autoradiography with [125I]A-85380 and [125I]α-bungarotoxin. Levels of mRNA encoding nAChR subunits were measured using quantitative real-time PCR (qPCR). We show that the number of α4β2 nAChR binding sites is lower globally in the SHR brain compared to WKY in the absence of significant differences in mRNA levels, with the exception of lower α4 mRNA in cerebellum of SHR compared to WKY. Further, nAChR deficits were subtype- specific because no strain difference was found in α7 nAChR binding or α7 mRNA levels. Our results suggest that the lower α4β2 nAChR number in SHR compared to WKY may be a consequence of dysfunctional post-transcriptional regulation of nAChRs. PMID:21824140

  18. 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.

  19. 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

  20. Chronic imipramine treatment differentially alters the brain and plasma amino acid metabolism in Wistar and Wistar Kyoto rats.

    PubMed

    Nagasawa, Mao; Otsuka, Tsuyoshi; Yasuo, Shinobu; Furuse, Mitsuhiro

    2015-09-05

    In the present study, the amino acids which have the possibility for the therapeutic efficacy of imipramine were explored and compared between Wistar Kyoto rats, an animal model of depression, and Wistar rats as a normal model. The antidepressant-like effect caused by chronic imipramine treatment was confirmed by decreased immobility in the forced swimming test. Chronic imipramine administration altered the amino acid dynamics in the brain. In the striatum, the concentrations of asparagine, glutamine and methionine were significantly increased by chronic imipramine administration. In the thalamus and hypothalamus, chronic imipramine administration significantly decreased the valine concentration. On the other hand, no amino acid was altered by chronic imipramine administration in the hippocampus, brain stem and cerebellum. In addition, lower concentration of asparagine in the prefrontal cortex of WKY rats was improved by chronic imipramine administration. This amelioration only in WKY rats may be a specific effect of chronic imipramine administration under the depressive state. In conclusion, chronic imipramine administration altered the several amino acid dynamics in the brain. Modification of the amino acid metabolism in the brain may provide a new strategy in the development of therapeutic treatment of major depression.

  1. 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

  2. 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.

  3. Clinical and pathological manifestations of cardiovascular disease in rat models: the influence of acute ozone exposure.

    PubMed

    Ramot, Yuval; Kodavanti, Urmila P; Kissling, Grace E; Ledbetter, Allen D; Nyska, Abraham

    2015-01-01

    Rodent models of cardiovascular diseases (CVD) and metabolic disorders are used for examining susceptibility variations to environmental exposures. However, cross-model organ pathologies and clinical manifestations are often not compared. We hypothesized that genetic CVD rat models will exhibit baseline pathologies and will thus express varied lung response to acute ozone exposure. Male 12-14-week-old healthy Wistar Kyoto (WKY), Wistar (WIS), and Sprague-Dawley (SD) rats and CVD-compromised spontaneously hypertensive (SH), fawn-hooded hypertensive (FHH), stroke-prone SH (SHSP), obese SH heart-failure (SHHF), obese diabetic JCR (JCR) rats were exposed to 0.0, 0.25, 0.5, or 1.0 ppm ozone for 4 h and clinical biomarkers, and lung, heart and kidney pathologies were compared immediately following (0-h) or 20-h later. Strain differences were observed between air-exposed CVD-prone and WKY rats in clinical biomarkers and in kidney and heart pathology. Serum cholesterol was higher in air-exposed obese SHHF and JCR compared to other air-exposed strains. Ozone did not produce lesions in the heart or kidney. CVD-prone and SD rats demonstrated glomerulopathy and kidney inflammation (WKY = WIS = SH < SD = SHSP < SHHF < JCR = FHH) regardless of ozone. Cardiac myofiber degeneration was evident in SH, SHHF, and JCR, while only JCR tends to have inflammation in coronaries. Lung pathology in air-exposed rats was minimal in all strains except JCR. Ozone induced variable alveolar histiocytosis and bronchiolar inflammation; JCR and SHHF were less affected. This study provides a comparative account of the clinical manifestations of disease and early-life organ pathologies in several rat models of CVD and their differential susceptibility to lung injury from air pollutant exposure.

  4. 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

  5. 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

  6. 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

  7. Endothelium-dependent relaxation in pulmonary arteries of L-NAME-treated Wistar and stroke-prone spontaneously hypertensive rats.

    PubMed

    Sekiguchi, Fumiko; Yamamoto, Kazuo; Matsuda, Kyoko; Kawata, Kyoko; Negishi, Maki; Shinomiya, Kazuaki; Shimamur, Keiichi; Sunano, Satoru

    2002-10-01

    To evaluate whether the elevated blood pressure induced by chronic treatment with N(omega)-nitro-L-arginine methyl ester (L-NAME) contributes to an impairment of endothelium-dependent relaxation (EDR), the effects of chronic treatment of Wistar rats with L-NAME on systolic blood pressure, pulmonary arterial blood pressure and EDR of the pulmonary arteries were studied and compared with those of stroke-prone spontaneously hypertensive rats (SHRSP). While the systolic blood pressure (SBP) of Wistar rats was increased above that of controls by chronic treatment with L-NAME, it was still significantly lower than that of SHRSP. Chronic treatment with L-NAME did not affect pulmonary arterial blood pressure. On the other hand, the pulmonary arterial blood pressure of SHRSP was slightly but significantly higher than that of the control normotensive Wistar Kyoto rats (WKY). EDR in response to acetylcholine in the pulmonary artery of L-NAME-treated rats was significantly smaller than that in control Wistar rats. The EDR markedly increased in the presence of L-arginine and completely disappeared in the presence of N(omega)-nitro-L-arginine. Indomethacin hardly affected EDR. In preparations from SHRSP, the EDR was not different from that in those from WKY. Relaxation induced by sodium nitroprusside was identical in all preparations. Elevation of SBP and the impairment of EDR observed in L-NAME-treated rats recovered two weeks following cessation of treatment. These results suggest that the impaired EDR in the pulmonary artery of L-NAME-treated rats is not due to an L-NAME-induced increase in blood pressure but due to the inhibition of nitric oxide synthase by the drug remaining in the endothelium.

  8. Unaltered caffeine-induced relaxation in the aorta of stroke-prone spontaneously hypertensive rats (SHRSP).

    PubMed

    Sekiguchi, Fumiko; Miyake, Yoshimasa; Kashimoto, Takafumi; Sunano, Satoru

    2002-04-01

    Caffeine-induced relaxation was studied in aortic segments from Wistar Kyoto rats (WKY) and stroke-prone spontaneously hypertensive rats (SHRSP). Although acetylcholine-induced endothelium-dependent relaxation was impaired in preparations from SHRSP, the relaxation induced by caffeine was identical in both groups. In addition, caffeine-induced relaxation was not affected by removal of the endothelium in either group. The relaxation induced by N6,2'-O-dibutyryladenosine 3':5'-cyclic monophosphate (db-cAMP), a membrane-permeable analog of adenosine 3':5'-cyclic monophosphate (cAMP), was identical in both groups. No significant difference was observed in the increase in cAMP content induced by caffeine in the aortic smooth muscle between the groups, although the basal content was significantly higher in preparations from SHRSP. These results suggest that the relaxation induced by caffeine in these preparations is brought about by its direct effect on smooth muscle and that the response of the smooth muscle to caffeine, including cAMP production, is not altered in preparations from SHRSP compared with those from WKY.

  9. Silencing salusin-β attenuates cardiovascular remodeling and hypertension in spontaneously hypertensive rats

    PubMed Central

    Ren, Xing-Sheng; Ling, Li; Zhou, Bing; Han, Ying; Zhou, Ye-Bo; Chen, Qi; Li, Yue-Hua; Kang, Yu-Ming; Zhu, Guo-Qing

    2017-01-01

    Salusin-β is a bioactive peptide involved in vascular smooth muscle cell proliferation, vascular fibrosis and hypertension. The present study was designed to determine the effects of silencing salusin-β on hypertension and cardiovascular remodeling in spontaneously hypertensive rats (SHR). Thirteen-week-old male SHR and normotensive Wistar-Kyoto rats (WKY) were subjected to intravenous injection of PBS, adenoviral vectors encoding salusin-β shRNA (Ad-Sal-shRNA) or a scramble shRNA. Salusin-β levels in plasma, myocardium and mesenteric artery were increased in SHR. Silencing salusin-β had no significant effect on blood pressure in WKY, but reduced blood pressure in SHR. It reduced the ratio of left ventricle weight to body weight, cross-sectional areas of cardiocytes and perivascular fibrosis, and decreased the media thickness and the media/lumen ratio of arteries in SHR. Silencing salusin-β almost normalized plasma norepinephrine and angiotensin II levels in SHR. It prevented the upregulation of angiotensin II and AT1 receptors, and reduced the NAD(P)H oxidase activity and superoxide anion levels in myocardium and mesenteric artery of SHR. Knockdown of salusin-β attenuated cell proliferation and fibrosis in vascular smooth muscle cells from SHR. These results indicate that silencing salusin-β attenuates hypertension and cardiovascular remodeling in SHR. PMID:28230187

  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.

  11. 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.

  12. Atypical microglial response to biodiesel exhaust in healthy and hypertensive rats.

    PubMed

    Mumaw, Christen L; Surace, Michael; Levesque, Shannon; Kodavanti, Urmila P; Kodavanti, Prasada Rao S; Royland, Joyce E; Block, Michelle L

    2017-03-01

    Accumulating evidence suggests a deleterious role for urban air pollution in central nervous system (CNS) diseases and neurodevelopmental disorders. Microglia, the resident innate immune cells and sentinels in the brain, are a common source of neuroinflammation and are implicated in air pollution-induced CNS effects. While renewable energy, such as soy-based biofuel, is of increasing public interest, there is little information on how soy biofuel may affect the brain, especially in people with preexisting disease conditions. To address this, male spontaneously hypertensive rats (SHR) and normotensive Wistar Kyoto (WKY) rats were exposed to 100% Soy-based Biodiesel Exhaust (100SBDE; 0, 50, 150 and 500μg/m(3)) by inhalation, 4h/day for 4 weeks (5 days/week). Ionized calcium-binding adapter molecule-1 (IBA-1) staining of microglia in the substantia nigra revealed significant changes in morphology with 100SBDE exposure in rats from both genotypes, where SHR were less sensitive. Aconitase activity was inhibited in the frontal cortex and cerebellum of WKY rats exposed to 100SBDE. No consistent changes occurred in pro-inflammatory cytokine expression, nitrated protein, or arginase1 expression in brain regions from either rat strain exposed to 100SBDE. However, while IBA-1 mRNA expression was not modified, CX3CR1 mRNA expression was lower in the striatum of 100SBDE exposed rats regardless of genotype, suggesting a downregulation of the fractalkine receptor on microglia in this brain region. Together, these data indicate that while microglia are detecting and responding to 100SBDE exposure with changes in morphology, there is reduced expression of CX3CR1 regardless of genetic background and the activation response is atypical without traditional inflammatory markers of M1 or M2 activation in the brain.

  13. Enhanced tubuloglomerular feedback activity in rats developing spontaneous hypertension.

    PubMed

    Dilley, J R; Arendshorst, W J

    1984-10-01

    Tubular microperfusion was used to evaluate tubuloglomerular feedback (TGF)-mediated changes in single nephron glomerular filtration rate (SNGFR) and stop-flow pressure (SFP) in euvolemic 6- and 11- to 14-wk-old spontaneously hypertensive rats (SHR) and normotensive Wistar-Kyoto rats (WKY). Young SHR compared with WKY had an elevated mean arterial pressure (107 vs. 90 mmHg, P less than 0.001) and a lower proximally measured SNGFR (14 vs. 17 nl/min, P less than 0.001) with no loop perfusion. Perfusion at 32 nl/min produced a greater decrease in SNGFR of SHR (6 vs. 2 nl/min, P less than 0.001). Although basal SFPs were identical (39 mmHg), loop perfusion elicited a greater maximal decline in SFP (-10 vs. -4 mmHg, P less than 0.001) and reactivity of SFP (-1.2 vs. -0.5 mmHg X min X nl-1, P less than 0.001) in young SHR; a lower rate produced a half-maximal decrease in SFP (7 vs. 10 nl/min, P less than 0.02). In adult rats, SNGFRs with no flow through Henle's loop were the same (27 and 28 nl/min) and perfusion at 32 nl/min produced similar decrements in SNGFR (-13 vs. -11 nl/min). The maximal change in SFP was greater in adult SHR (-12 vs. -10 mmHg, P less than 0.02), but there were no strain differences in maximal SFP reactivity (-1.8 vs. -1.3 mmHg X min X nl-1) and the rate eliciting half-maximal SFP changes (12 vs. 12 nl/min). Reduction of arterial pressure to the normotensive range did not alter responses in either age group of SHR.(ABSTRACT TRUNCATED AT 250 WORDS)

  14. Effects of Bay K 8644 in aorta from spontaneously hypertensive and Wistar Kyoto rats of different ages.

    PubMed

    Hernández, M C; Salaices, M; Ponte, A; Alonso, M J; Sánchez-Ferrer, C F; Marín, J

    1995-08-01

    1. The Ca(2+)-channel agonist, Bay K 8644, induced small contractions in aortae from Wistar-Kyoto (WKY) rats of 5-week-, 3-month-, 1-year- and 1.5-year-old, which were unaltered with age. These contractions were increased by partial depolarization with 15 mM K+. 2. In segments from spontaneously hypertensive rats (SHR), the contractions obtained in both situations were similar and equivalent to those observed in segments from normotensive animals partially depolarized. Responses to Bay K 8644 were modified by age only in tissues from the SHR, the responses to this agent in basal conditions being increased in tissues from 3-month- and 1-year-old animals and depressed in those from 1.5-year SHR. 3. A reduction of the response to Bay K 8644 was observed in partial depolarized endothelium denuded segments from WKY of all ages, and no modification in basal situation. However, the direct contractions induced by Bay K 8644 in aortae from 3-month- and 1.5-year-old SHR were reduced by endothelium removal. 4. These results suggest that: (a) in the hypertensive strain the voltage-gated Ca2+ channels seem to be partially activated; (b) the direct contractions induced by Bay K 8644 were unaltered by age in aortae from WKY but increased in tissues from SHR of 3-month-and-1-year old and depressed in those from 1.5 years, and (c) the contractions evoked by Bay K 8644 seem to involve an endothelium-derived contracting factor in aortae from both strains, or the endothelium produces a partial depolarization of vascular smooth muscle that increases the responsiveness to Bay K 8644.

  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. Comparative analysis of the central CCK system in Fawn Hooded and Wistar Kyoto rats: extended localisation of CCK-A receptors throughout the rat brain using a novel radioligand.

    PubMed

    Lodge, D J; Lawrence, A J

    2001-06-15

    The neuropeptide cholecystokinin has been implicated in the actions of a number of central processes including anxiety and reward. For this reason, the aim of the present study was to compare the density of CCK-A and -B receptors and the mRNA encoding preproCCK throughout the brains of an alcohol-preferring (Fawn Hooded) rat strain with that of a non-alcohol-preferring (Wistar Kyoto) strain of rat. Our study revealed significant differences with regard to the central CCK system of the FH compared to the WKY rat, including differences in CCK-A receptor binding throughout the dorsal medulla, and altered CCK-B binding density throughout the cerebral cortex and reticular nucleus of the thalamus. The most striking result, given the altered behavioural phenotype of the FH rat, was the 33% lower density of CCKmRNA measured throughout the ventral tegmental area of the FH rat when compared to the WKY. This study also reports on a protocol to utilise a novel radioligand, [125I]-D-Tyr-Gly-A-71378, for autoradiographic detection of CCK-A receptors throughout the rat brain. As previously reported, CCK-A receptors were located throughout the area postrema, interpeduncular nucleus and nucleus tractus solitarii; however, binding to CCK-A receptors was also visualised throughout the medial pre-optic area, the arcuate nucleus and the circumventricular regions of the ventral hypothalamus, regions known to contain CCK-A receptors but which were previously undetectable using autoradiography in rat brain.

  17. Ocular Changes in TgF344-AD Rat Model of Alzheimer's Disease

    PubMed Central

    Tsai, Yuchun; Lu, Bin; Ljubimov, Alexander V.; Girman, Sergey; Ross-Cisneros, Fred N.; Sadun, Alfredo A.; Svendsen, Clive N.; Cohen, Robert M.; Wang, Shaomei

    2014-01-01

    Purpose. Alzheimer's disease (AD) is the most common neurodegenerative disorder characterized by progressive decline in learning, memory, and executive functions. In addition to cognitive and behavioral deficits, vision disturbances have been reported in early stage of AD, well before the diagnosis is clearly established. To further investigate ocular abnormalities, a novel AD transgenic rat model was analyzed. Methods. Transgenic (Tg) rats (TgF344-AD) heterozygous for human mutant APPswe/PS1ΔE9 and age-matched wild type (WT) rats, as well as 20 human postmortem retinal samples from both AD and healthy donors were used. Visual function in the rodent was analyzed using the optokinetic response. Immunohistochemistry on retinal and brain sections was used to detect various markers including amyloid-β (Aβ) plaques. Results. As expected, Aβ plaques were detected in the hippocampus, cortex, and retina of Tg rats. Plaque-like structures were also found in two AD human whole-mount retinas. The choroidal thickness was significantly reduced in both Tg rat and in AD human eyes when compared with age-matched controls. Tg rat eyes also showed hypertrophic retinal pigment epithelial cells, inflammatory cells, and upregulation of complement factor C3. Although visual acuity was lower in Tg than in WT rats, there was no significant difference in the retinal ganglion cell number and retinal vasculature. Conclusions. Further studies are needed to elucidate the significance and mechanisms of this pathological change and luminance threshold recording from the superior colliculus. PMID:24398104

  18. N-acetylcysteine improves renal hemodynamics in rats with cisplatin-induced nephrotoxicity.

    PubMed

    Abdelrahman, Aly M; Al Salam, Suhail; AlMahruqi, Ahmed S; Al husseni, Ishaq S; Mansour, Mohamed A; Ali, Badreldin H

    2010-01-01

    This work investigated the effect of N-acetylcysteine (NAC), on renal hemodynamics in cisplatin (CP)-induced nephrotoxicity in Wistar-Kyoto (WKY) rats. The animals were divided into four groups (n = 5 or 6). The first and second groups received normal saline (control) and intraperitoneal (i.p.) N-acetylcysteine (500 mg kg(-1) per day for 9 days), respectively. The third and fourth groups were given a single intraperitoneal (i.p.) injection of CP (5 mg kg(-1)) and an i.p. injection of CP (5 mg kg(-1)) together with i.p. NAC (500 mg kg(-1) per day for 9 days), respectively. At the end of the experiment, rats were anesthetized and blood pressure and renal blood flow were monitored, followed by intravenous (i.v.) injection of norepinephrine (NE) for measurement of renal vasoconstrictor responses. CP caused a significant reduction in renal blood flow but did not affect NE-induced renal vasoconstriction. In addition, CP significantly increased plasma concentrations of urea and creatinine and urinary N-acetyl-beta-D-glucosaminidase (NAG) activity and kidney relative weight. CP decreased body weight and creatinine clearance. Histopathologically, CP caused remarkable renal damage compared with control. NAC alone did not produce any significant change in any of the variables measured. However, NAC significantly ameliorated CP-induced hemodynamic, biochemical and histopathological changes. The concentration of platinum in the kidneys of CP ? NAC treated rats was less than in CP-treated rats by 37%. The results show that administration of i.p. NAC (500 mg kg(-1) per day for 9 days) reversed the renal hemodynamic changes as well as the biochemical and histopathological indices of CP-induced nephrotoxicity in WKY rats.

  19. Performance on a strategy set shifting task in rats following adult or adolescent cocaine exposure

    PubMed Central

    Kantak, Kathleen M.; Barlow, Nicole; Tassin, David H.; Brisotti, Madeline F.; Jordan, Chloe J

    2014-01-01

    Rationale Neuropsychological testing is widespread in adult cocaine abusers, but lacking in teens. Animal models may provide insight into age-related neuropsychological consequences of cocaine exposure. Objectives Determine whether developmental plasticity protects or hinders behavioral flexibility after cocaine exposure in adolescent vs. adult rats. Methods Using a yoked-triad design, one rat controlled cocaine delivery and the other two passively received cocaine or saline. Rats controlling cocaine delivery (1.0 mg/kg) self-administered for 18 sessions (starting P37 or P77), followed by 18 drug-free days. Rats next were tested in a strategy set shifting task, lasting 11–13 sessions. Results Cocaine self-administration did not differ between age groups. During initial set formation, adolescent-onset groups required more trials to reach criterion and made more errors than adult-onset groups. During the set shift phase, rats with adult-onset cocaine self-administration experience had higher proportions of correct trials and fewer perseverative + regressive errors than age-matched yoked-controls or rats with adolescent-onset cocaine self-administration experience. During reversal learning, rats with adult-onset cocaine experience (self-administered or passive) required fewer trials to reach criterion and the self-administering rats made fewer perseverative + regressive errors than yoked-saline rats. Rats receiving adolescent-onset yoked-cocaine had more trial omissions and longer lever press reaction times than age-matched rats self-administering cocaine or receiving yoked-saline. Conclusions Prior cocaine self-administration may impair memory to reduce proactive interference during set shifting and reversal learning in adult-onset but not adolescent-onset rats (developmental plasticity protective). Passive cocaine may disrupt aspects of executive function in adolescent-onset but not adult-onset rats (developmental plasticity hinders). PMID:24800898

  20. 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

  1. [Cardiohemodynamics and efficiency Frank-Starling mechanism in spontaneously hypertensive rats].

    PubMed

    Dorofeieva, N O; Kuz'menko, M O; Shimans'ka, T V; Sagach, V F

    2012-01-01

    We studied cardiohemodynamics and efficiency Frank-Starling mechanism in 6-month-old spontaneously hypertensive rats (SHR) and age-matched Wistar rats, using pressure-volume (PV) conductance catheter system (Millar Instruments, Houston, TX) to evaluate systolic and diastolic function in vivo. Rats were anesthetized with urethane. Cardiohemodynamics analyzed using PVAN 3.6 (Millar Instruments). We found that systolic and diastolic function of the heart in spontaneously hypertensive rats were lower, than in controls. We have shown, inhibition of the efficiency Frank-Starling mechanism, increasing arterial stiffness in spontaneously hypertensive rats. It's shown, less efficiency heart work, with more energy and more oxygen consumption in spontaneously hypertensive rats, may be associated with increasing arterial stiffness and decrease functional reserve of the heart.

  2. Nicotine-stimulated release of [3H]norepinephrine is reduced in the hippocampus of an animal model of attention-deficit/hyperactivity disorder, the spontaneously hypertensive rat.

    PubMed

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

    2014-07-14

    Attention-deficit/hyperactivity disorder (ADHD) is a heterogeneous, developmental disorder, and is one of the most common child-psychiatric disorders. It is also a risk factor for early smoking and adult nicotine dependence. Nicotine has been shown to improve symptoms associated with ADHD, including problems with attention, working memory and response inhibition. Norepinephrine, a neurotransmitter involved in attention, is highly implicated in ADHD, and often targeted in the treatment thereof. In the present study we investigated nicotine׳s effect on release of norepinephrine in the hippocampus of a validated rat model of ADHD, the spontaneously hypertensive rat (SHR), as well as in two control strains: Wistar-Kyoto rats (WKY) and Sprague-Dawley rats (SD). Hippocampal slices obtained from male SHR, WKY and SD (postnatal day 31-33) were pre-incubated with radioactively labelled norepinephrine ([3H]NE) and perfused with buffer. The slices were stimulated by exposure to different concentrations of nicotine (1, 10, 100 or 1000 µM) for 1 min at 2 intervals (S1 and S2, separated by 20 min). Following a 10 min wash, slices were stimulated with 25 mM potassium. Since glutamate and GABA receptor function differ in SHR and WKY, we investigated the possible involvement of AMPA and GABA(A) receptors in nicotine (100 µM)-stimulated release of hippocampal [3H]NE in each of the strains by blocking these receptors with CNQX (AMPA receptor antagonist, 10 µM) or bicuculline (GABAA receptor antagonist, 30 µM) respectively. Nicotine-stimulated release (S1) of [3H]NE from SHR hippocampal slices was less than that of WKY and SD, at 100 µM and 1000 µM nicotine, suggesting reduced density and/or function of nicotinic receptors in SHR hippocampus. Nicotine-stimulated release of [3H]NE in response to S2 was reduced compared to S1 in all strains, indicating desensitization of receptors involved in stimulation of [3H]NE by nicotine. Potassium-stimulated release of [3H]NE following the

  3. Chronic Stress Induces Structural Alterations in Splenic Lymphoid Tissue That Are Associated with Changes in Corticosterone Levels in Wistar-Kyoto Rats

    PubMed Central

    Hernandez, María Eugenia; Martinez-Mota, Lucia; Salinas, Citlaltepetl; Marquez-Velasco, Ricardo; Hernandez-Chan, Nancy G.; Morales-Montor, Jorge; Pérez-Tapia, Mayra; Streber, María L.; Granados-Camacho, Ivonne; Becerril, Enrique; Javier, Baquera-Heredia; Pavón, Lenin

    2013-01-01

    Major depressive disorder patients present chronic stress and decreased immunity. The Wistar-Kyoto rat (WKY) is a strain in which the hypothalamic-pituitary-adrenal axis is overactivated. To determine whether chronic stress induces changes in corticosterone levels and splenic lymphoid tissue, 9-week-old male rats were subject to restraint stress (3 h daily), chemical stress (hydrocortisone treatment, 50 mg/Kg weight), mixed stress (restraint plus hydrocortisone), or control treatment (without stress) for 1, 4, and 7 weeks. The serum corticosterone levels by RIA and spleens morphology were analyzed. Corticosterone levels as did the structure, size of the follicles and morphology of the parenchyma (increase in red pulp) in the spleen, varied depending on time and type of stressor. These changes indicate that chronic stress alters the immune response in the spleen in WKY rats by inducing morphological changes, explaining in part the impaired immunity that develops in organisms that are exposed to chronic stress. PMID:23533999

  4. 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

  5. Cardiopulmonary responses in spontaneously hypertensive and Wistar-Kyoto rats exposed to concentrated ambient particles from Detroit, Michigan.

    PubMed

    Rohr, Annette C; Wagner, James G; Morishita, Masako; Kamal, Ali; Keeler, Gerald J; Harkema, Jack R

    2010-05-01

    Toxicological effects have been observed in rats exposed to concentrated ambient particles (CAPs) from different regions of the United States. The objective of this study was to evaluate the cardiopulmonary and systemic effects of CAPs in Detroit. The authors stationed a mobile concentrator at a location near major traffic and industrial sources. Spontaneously hypertensive (SH) and Wistar-Kyoto (WKY) rats were exposed to fine CAPs (diameter < 0.1-2.5 microm) 8 h/day for 13 consecutive days. Animals were implanted with telemeters, and electrocardiogram data were recorded continuously. Bronchoalveolar lavage (BAL) fluid and plasma were analyzed. Comprehensive exposure monitoring was conducted, including CAPs components. CAPs exposure concentrations were 103-918 microg/m(3) (mean = 502 microg/m(3)). The authors found no statistically significant differences in heart rate or SDNN (standard deviation of the normal-to-normal intervals), a measure of heart rate variability, between CAPs-exposed and control rats. The authors found significantly higher levels of C-reactive protein in the serum of CAPs-exposed SH rats compared with air-exposed animals. Protein in BAL fluid was elevated in WKY rats exposed to CAPs. Measurement of trace metals in lung tissue showed elevated concentrations of V, Sb, La, and Ce in CAPs-exposed SH animals versus controls. These elements are generally associated with oil combustion, oil refining, waste incineration, and traffic. Examination of wind rose data from the exposure period confirmed that the predominant wind direction was SSW, the direction of many of the aforementioned sources. These results indicate that ambient particles in Detroit can cause mild pulmonary and systemic changes in rats, and suggest the importance of local PM(2.5) sources in these effects.

  6. Impulsive choice behavior in four strains of rats: evaluation of possible models of Attention-Deficit/Hyperactivity Disorder.

    PubMed

    Garcia, Ana; Kirkpatrick, Kimberly

    2013-02-01

    Several studies have examined impulsive choice behavior in spontaneously hypertensive rats (SHRs) as a possible pre-clinical model for Attention-Deficit/Hyperactivity Disorder (ADHD). However, this strain was not specifically selected for the traits of ADHD and as a result their appropriateness as a model has been questioned. The present study investigated whether SHRs would exhibit impulsive behavior in comparison to their control strain, Wistar Kyoto (WKY) rats. In addition, we evaluated a strain that has previously shown high levels of impulsive choice, the Lewis (LEW) rats and compared them with their source strain, Wistar (WIS) rats. In the first phase, rats could choose between a smaller-sooner (SS) reward of 1 pellet after 10 s and a larger-later (LL) reward of 2 pellets after 30 s. Subsequently, the rats were exposed to increases in LL reward magnitude and SS delay. These manipulations were designed to assess sensitivity to magnitude and delay within the choice task to parse out possible differences in using the strains as models of specific deficits associated with ADHD. The SHR and WKY strains did not differ in their choice behavior under either delay or magnitude manipulations. In comparison to WIS, LEW showed deficits in choice behavior in the delay manipulation, and to a lesser extent in the magnitude manipulation. An examination of individual differences indicated that the SHR strain may not be sufficiently homogeneous in their impulsive choice behavior to be considered as a viable model for impulse control disorders such as ADHD. The LEW strain may be worthy of further consideration for their suitability as an animal model.

  7. Impulsive choice behavior in four strains of rats: Evaluation of possible models of Attention Deficit/Hyperactivity Disorder

    PubMed Central

    Garcia, Ana; Kirkpatrick, Kimberly

    2012-01-01

    Several studies have examined impulsive choice behavior in spontaneously hypertensive rats (SHRs) as a possible pre-clinical model for Attention-Deficit/Hyperactivity Disorder (ADHD). However, this strain was not specifically selected for the traits of ADHD and as a result their appropriateness as a model has been questioned. The present study investigated whether SHRs would exhibit impulsive behavior in comparison to their control strain, Wistar Kyoto (WKY) rats. In addition, we evaluated a strain that has previously shown high levels of impulsive choice, the Lewis (LEW) rats and compared them with their source strain, Wistar (WIS) rats. In the first phase, rats could choose between a Smaller-sooner (SS) reward of 1 pellet after 10 s and a Larger-later (LL) reward of 2 pellets after 30 s. Subsequently, the rats were exposed to increases in LL reward magnitude and SS delay. These manipulations were designed to assess sensitivity to magnitude and delay within the choice task to parse out possible differences in using the strains as models of specific deficits associated with ADHD. The SHR and WKY strains did not differ in their choice behavior under either delay or magnitude manipulations. In comparison to WIS, LEW showed deficits in choice behavior in the delay manipulation, and to a lesser extent in the magnitude manipulation. An examination of individual differences indicated that the SHR strain may not be sufficiently homogeneous in their impulsive choice behavior to be considered as a viable model for impulse control disorders such as ADHD. The LEW strain may be worthy of further consideration for their suitability as an animal model. PMID:23085479

  8. Activities of adenosine deaminase (ADA) and purine nucleoside phosphorylase (PNP) on undernourished and renourished rats' thymus.

    PubMed

    Feliu, M S.; Slobodianik, N H.

    2001-02-01

    We studied the effect of administration of a low quality dietary protein, from weaning onwards, on the thymus of undernourished rats and the posterior effect of refeeding with a high quality dietary protein. Changes in thymus weight and the activity of Adenosine Deaminase (ADA) and Purine Nucleoside Phosphorylase (PNP) on thymus, were determined. Wistar rats were suckled in groups of 14-16 per dam since birth to weaning (23 days) to obtain undernutrition. At weaning, a group of 14-16 rats received pre-cooked maize flour (Protein content: 6.5%) for 18 days. One group was sacrificed (M) and the other rats were refed with the casein diet (Protein content: 20%) during 20 days (R). The age-matched control groups were fed stock diet since 40 (C40) and 60 (C60) days of age, respectively. At the end of the experimental period, body (Bw) and thymus weight were determined. ADA and PNP activities were determined in thymocyte suspensions. Highly significant differences in thymus weight-expressed as mg or mg/Bw(0.75)-and the activity of ADA and PNP were observed in rats fed the experimental diet containing maize flour, when compared to the respective age-matched control. No statistical differences were observed between R and C60.The administration of a high quality dietary protein to undernourished weanling rats is capable to reverse the damage produced by the low quality dietary protein on thymus weight and ADA and PNP thymus activities.

  9. Longitudinal Analysis of Calorie Restriction on Rat Taste Bud Morphology and Expression of Sweet Taste Modulators

    PubMed Central

    Cai, Huan; Daimon, Caitlin M.; Cong, Wei-na; Wang, Rui; Chirdon, Patrick; de Cabo, Rafael; Sévigny, Jean; Maudsley, Stuart; Martin, Bronwen

    2014-01-01

    Calorie restriction (CR) is a lifestyle intervention employed to reduce body weight and improve metabolic functions primarily via reduction of ingested carbohydrates and fats. Taste perception is highly related to functional metabolic status and body adiposity. We have previously shown that sweet taste perception diminishes with age; however, relatively little is known about the effects of various lengths of CR upon taste cell morphology and function. We investigated the effects of CR on taste bud morphology and expression of sweet taste–related modulators in 5-, 17-, and 30-month-old rats. In ad libitum (AL) and CR rats, we consistently found the following parameters altered significantly with advancing age: reduction of taste bud size and taste cell numbers per taste bud and reduced expression of sonic hedgehog, type 1 taste receptor 3 (T1r3), α-gustducin, and glucagon-like peptide-1 (GLP-1). In the oldest rats, CR affected a significant reduction of tongue T1r3, GLP-1, and α-gustducin expression compared with age-matched AL rats. Leptin receptor immunopositive cells were elevated in 17- and 30-month-old CR rats compared with age-matched AL rats. These alterations of sweet taste–related modulators, specifically during advanced aging, suggest that sweet taste perception may be altered in response to different lengths of CR. PMID:24077597

  10. Interactions Between Corticotropin-Releasing Factor and the Serotonin 1A Receptor System on Acoustic Startle Amplitude and Prepulse Inhibition of the Startle Response in Two Rat Strains

    PubMed Central

    Conti, Lisa H.

    2011-01-01

    Both the neuropeptide, corticotropin-releasing factor (CRF) and the serotonin 1A (5-HT1A) receptor systems have been implicated in anxiety disorders and there is evidence that the two systems interact with each other to affect behavior. Both systems have individually been shown to affect prepulse inhibition (PPI) of the acoustic startle response. PPI is a form of sensorimotor gating that is reduced in patients with anxiety disorders including post-traumatic stress and panic disorder. Here, we examined whether the two systems interact or counteract each other to affect acoustic startle amplitude, PPI and habituation of the startle response. In experiment 1, Brown Norway (BN) and Wistar-Kyoto (WKY) rats were administered ether an intraperitoneal (IP) injection of saline or the 5-HT1A receptor agonist, 8-OH-DPAT 10 min prior to receiving an intracerebroventricular (ICV) infusion of either saline or CRF (0.3 µg). In a second experiment, rats were administered either an IP injection of saline or the 5-HT1A receptor antagonist, WAY 100,635 10 min prior to receiving an ICV infusion of saline or CRF. Thirty min after the ICV infusion, the startle response and PPI were assessed. As we have previously shown, the dose of CRF used in these experiments reduced PPI in BN rats and had no effect on PPI in WKY rats. Administration of 8-OH-DPAT alone had no effect on PPI in either rat strain when the data from the two strains were examined separately. Administration of 8-OHDPAT added to the effect of CRF in BN rats, and the combination of 8-OH-DPAT and CRF significantly reduced PPI in WKY rats. CRF alone had no effect on baseline startle amplitude in either rat strain, but CRF enhanced the 8-OH-DPAT-induced increase in startle in both strains. Administration of WAY 100,635 did not affect the CRF-induced change in PPI and there were no interactions between CRF and WAY 100,635 on baseline startle. The results suggest that activation of the 5-HT1A receptor can potentiate the effect of

  11. Ramelteon attenuates age-associated hypertension and weight gain in spontaneously hypertensive rats.

    PubMed

    Oxenkrug, Gregory F; Summergrad, Paul

    2010-06-01

    The neuroendocrine theory of aging suggests the common mechanisms of developmental (prereproductive) and aging (postreproductive) processes and identified a cluster of conditions (hypertension, obesity, dyslipidemia, type 2 diabetes, menopause, late onset depression, vascular cognitive impairment, impairment of immune defense, and some forms of cancer) as age-associated neuroendocrine disorders (AAND). Obesity, dyslipidemia, hypertension, and type 2 diabetes were later described as metabolic syndrome (MetS). Because melatonin attenuated development of MetS is age-dependent, that is, in young and old, but not in middle-aged rats, we studied the effect of the selective melatonin agonist, Ramelteon, on the two core symptoms of MetS/AAND: hypertension and body weight gain in spontaneously hypertensive (SHR) and normotensive Wistar-Kyoto male rats (WKY). SHR rats developed hypertension at the time of maximal weight gain that coincided with the onset of reproductive activity (8-10 weeks old). Chronic (but not acute) administration of Ramelteon (in drinking water, 8 mg/kg/day, from 4 to 12 weeks of age) attenuated age-associated increase of systolic blood pressure (tail-cuff method) by 45%, and age-associated body weight gain by 30%. Acute and chronic Ramelteon did not affect blood pressure and body weight in normotensive WKY rats. Ramelteon-induced attenuation of age-associated hypertension and weight gain suggests that Ramelteon might attenuate the other symptoms of MetS/AAND and might be useful in the treatment of MetS/AAND during puberty, menopause, and old age.

  12. Genetic, physiological and comparative genomic studies of hypertension and insulin resistance in the spontaneously hypertensive rat

    PubMed Central

    Hummel, Oliver; Garcia Diaz, Ana; Barrier, Marjorie; Alfazema, Neza; Norsworthy, Penny J.; Pravenec, Michal; Petretto, Enrico; Hübner, Norbert

    2017-01-01

    ABSTRACT We previously mapped hypertension-related insulin resistance quantitative trait loci (QTLs) to rat chromosomes 4, 12 and 16 using adipocytes from F2 crosses between spontaneously hypertensive (SHR) and Wistar Kyoto (WKY) rats, and subsequently identified Cd36 as the gene underlying the chromosome 4 locus. The identity of the chromosome 12 and 16 genes remains unknown. To identify whole-body phenotypes associated with the chromosome 12 and 16 linkage regions, we generated and characterised new congenic strains, with WKY donor segments introgressed onto an SHR genetic background, for the chromosome 12 and 16 linkage regions. We found a >50% increase in insulin sensitivity in both the chromosome 12 and 16 strains. Blood pressure and left ventricular mass were reduced in the two congenic strains consistent with the congenic segments harbouring SHR genes for insulin resistance, hypertension and cardiac hypertrophy. Integrated genomic analysis, using physiological and whole-genome sequence data across 42 rat strains, identified variants within the congenic regions in Upk3bl, RGD1565131 and AABR06087018.1 that were associated with blood pressure, cardiac mass and insulin sensitivity. Quantitative trait transcript analysis across 29 recombinant inbred strains showed correlation between expression of Hspb1, Zkscan5 and Pdgfrl with adipocyte volume, systolic blood pressure and cardiac mass, respectively. Comparative genome analysis showed a marked enrichment of orthologues for human GWAS-associated genes for insulin resistance within the syntenic regions of both the chromosome 12 and 16 congenic intervals. Our study defines whole-body phenotypes associated with the SHR chromosome 12 and 16 insulin-resistance QTLs, identifies candidate genes for these SHR QTLs and finds human orthologues of rat genes in these regions that associate with related human traits. Further study of these genes in the congenic strains will lead to robust identification of the underlying

  13. Lentil-based diets attenuate hypertension and large-artery remodelling in spontaneously hypertensive rats.

    PubMed

    Hanson, Matthew G; Zahradka, Peter; Taylor, Carla G

    2014-02-01

    Hypertension is a major risk factor for CVD, the leading cause of mortality worldwide. The prevalence of hypertension is expected to continue increasing, and current pharmacological treatments cannot alleviate all the associated problems. Pulse crops have been touted as a general health food and are now being studied for their possible effects on several disease states including hypertension, obesity and diabetes. In the present study, 15-week-old spontaneously hypertensive rats (SHR) were fed diets containing 30% w/w beans, peas, lentils, chickpeas, or mixed pulses or a pulse-free control diet for 4 weeks. Normotensive Wistar-Kyoto (WKY) rats were placed on a control diet. Pulse wave velocity (PWV) was measured weekly, while blood pressure (BP) was measured at baseline and week 4. Fasting serum obtained in week 4 of the study was analysed for circulating lipids. A histological analysis was carried out on aortic sections to determine vascular geometry. Of all the pulse varieties studied, lentils were found to be able to attenuate the rise in BP in the SHR model (P< 0·05). Lentils were able to decrease the media:lumen ratio and media width of the aorta. The total cholesterol (TC), LDL-cholesterol (LDL-C) and HDL-cholesterol levels of rats fed the pulse-based diets were found to be lower when compared with those of the WKY rat and SHR controls (P< 0·05). Although all pulses reduced circulating TC and LDL-C levels in the SHR, only lentils significantly reduced the rise in BP and large-artery remodelling in the SHR, but had no effect on PWV. These results indicate that the effects of lentils on arterial remodelling and BP in the SHR are independent of circulating LDL-C levels.

  14. Long-term effects of type 2 diabetes mellitus on heart rhythm in the Goto-Kakizaki rat.

    PubMed

    Howarth, Frank C; Jacobson, Michael; Shafiullah, Mohamed; Adeghate, Ernest

    2008-03-01

    In vivo biotelemetry studies have demonstrated a variety of heart rhythm disturbances in type 1 diabetes mellitus. In the streptozotocin (STZ)-induced diabetic rat, these disturbances have included reductions in heart rate (HR) and heart rate variability (HRV) and an electrocardiogram that displays prolonged QRS duration and Q-T interval. The aim of this study was to investigate the chronic effects of type 2 diabetes mellitus on heart rhythm in the Goto-Kakizaki (GK) rat. Transmitter devices were surgically implanted in the peritoneal cavity of young male GK and age-matched Wistar control rats. Electrodes from the transmitter were arranged in Einthoven bipolar lead II configuration. Electrocardiogram, physical activity and body temperature data were recorded in rats from age 2 to 15 months. Data were acquired for 2 weeks each month. Non-fasting blood glucose, glucose tolerance and body weight were measured periodically. In GK rats, growth rate and maximal attained body weight were significantly reduced and non-fasting blood glucose was progressively increased compared with age-matched Wistar control animals. Heart rate was significantly lower in GK compared with control rats at 2, 7 and 15 months of age. At 2 months of age, HR was 316 +/- 6 beats min(-1) in GK rats compared with 370 +/- 7 beats min(-1) in Wistar control animals. There was a progressive age-dependent decline in HRV in Wistar control rats; however, HRV in GK rats did not alter significantly with age. Heart rate variability was significantly reduced in GK compared with Wistar control rats at 2 and 7 months. At 2 months of age, HRV was 28 +/- 2 beats min(-1) in GK rats compared with 38 +/- 3 beats min(-1) in Wistar control rats. Reduced HR in GK rats may be an inherited characteristic. The absence of age-dependent reductions in HRV in GK rats may be a consequence of an underlying impairment of autonomic control which manifests at early age.

  15. Effects of High Fat Feeding on Liver Gene Expression in Diabetic Goto-Kakizaki Rats

    PubMed Central

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

    2012-01-01

    Effects of high fat diet (HFD) on obesity and, subsequently, on diabetes are highly variable and modulated by genetics in both humans and rodents. In this report, we characterized the response of Goto-Kakizaki (GK) rats, a spontaneous polygenic model for lean diabetes and healthy Wistar-Kyoto (WKY) controls, to high fat feeding from weaning to 20 weeks of age. Animals fed either normal diet or HFD were sacrificed at 4, 8, 12, 16 and 20 weeks of age and a wide array of physiological measurements were made along with gene expression profiling using Affymetrix gene array chips. Mining of the microarray data identified differentially regulated genes (involved in inflammation, metabolism, transcription regulation, and signaling) in diabetic animals, as well as the response of both strains to HFD. Functional annotation suggested that HFD increased inflammatory differences between the two strains. Chronic inflammation driven by heightened innate immune response was identified to be present in GK animals regardless of diet. In addition, compensatory mechanisms by which WKY animals on HFD resisted the development of diabetes were identified, thus illustrating the complexity of diabetes disease progression. PMID:23236253

  16. Diminution of the NMDA receptor NR2B subunit in cortical and subcortical areas of WAG/Rij rats.

    PubMed

    Karimzadeh, Fariba; Soleimani, Mansoureh; Mehdizadeh, Mehdi; Jafarian, Maryam; Mohamadpour, Maliheh; Kazemi, Hadi; Joghataei, Mohammad-Taghi; Gorji, Ali

    2013-12-01

    Modulation of glutamatergic NMDA receptors affects the synchronization of spike discharges in in WAG/Rij rats, a valid genetic animal model of absence epilepsy. In this study, we describe the alteration of NR2B subunit of NMDA receptors expression in WAG/Rij rats in different somatosensory cortical layers and in hippocampal CA1 area. Experimental groups were divided into four groups of six rats of both WAG/Rij and Wistar strains with 2 and 6 months of age. The distribution of NR2B receptors was assessed by immunohistochemical staining in WAG/Rij and compared with age-matched Wistar rats. The expression of NR2B subunit was significantly decreased in different somatosensory cortical layers in 2- and 6-month-old WAG/Rij rats. In addition, the distribution of NR2B in hippocampal CA1 area was lower in 6-month-old WAG/Rij compared with age-matched Wistar rats. The reduction of NR2B receptors in different brain areas points to disturbance of glutamate receptors expression in cortical and subcortical areas in WAG/Rij rats. An altered subunit assembly of NMDA receptors may underlie cortical hyperexcitability in absence epilepsy.

  17. PROLONGED PERFORMANCE OF A HIGH REPETITION LOW FORCE TASK INDUCES BONE ADAPTATION IN YOUNG ADULT RATS, BUT LOSS IN MATURE RATS

    PubMed Central

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

    2015-01-01

    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 mo of age) and 14 young adult (2.5–6.5 mo 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

  18. 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.

  19. Angiotensinase C mRNA and Protein Downregulations Are Involved in Ethanol-Deteriorated Left Ventricular Systolic Dysfunction in Spontaneously Hypertensive Rats

    PubMed Central

    Liu, Jinyao; Hakucho, Ayako; Fujimiya, Tatsuya

    2015-01-01

    The influences of angiotensinase C on ethanol-induced left ventricular (LV) systolic function were assessed in spontaneously hypertensive rats (SHRs). SHRs were fed by a liquid diet with or without ethanol for 49 days. The normotensive Wistar Kyoto rats (WKY) were fed by the liquid diet without ethanol and used as control. We evaluated LV systolic function, angiotensinase C mRNA and protein expressions, activation of the renin-angiotensin system (RAS), and the gene expressions of LV collagen (Col) III a1 and matrix metalloproteinases- (MMP-) 9. Compared to the WKY, LV systolic dysfunction (expressed by decreased fractional shortening and ejection fraction) was observed in the SHRs before ethanol treatment and further deteriorated by ethanol treatment. In the ethanol-treated SHRs, the following were observed: downregulations of angiotensinase C mRNA and protein, increased RAS activity with low collagen production as evidenced by angiotensin II and angiotensin type 1 receptor (AT1R) protein upregulation, AT1aR mRNA downregulation, and an MMP-9 mRNA expression upregulation trend with the downregulation of Col III a1 mRNA expression in LV. We conclude that chronic ethanol regimen is sufficient to promote the enhanced RAS activity-induced decrease in the production of cardiac collagen via downregulated angiotensinase C, leading to the further deterioration of LV systolic dysfunction in SHRs. PMID:26509155

  20. 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.

  1. Lack of evidence for a role for either the in utero or suckling periods in the exaggerated salt preference of the spontaneously hypertensive rat.

    PubMed

    Di Nicolantonio, Robert; Westcott, Kerryn T; Koutsis, Kathy; Wlodek, Mary E

    2005-11-15

    When offered as a choice with drinking water in two-bottle preference tests, the spontaneously hypertensive rats (SHR) of the Okamoto strain exhibit a marked preference for saline solutions. While this behaviour is thought to be in part genetically determined, the role of environmental influences-in particular, perinatal ones-are poorly understood. In this study, we have used combined embryo transfer and cross-fostering techniques between SHR and normotensive Wistar Kyoto (WKY) rats to delineate the relative roles of the prenatal and postnatal, suckling environment on the exaggerated saline preference of male SHR and WKY offspring at 20 weeks of age. We found, using two-bottle preference tests using water and 140 mmol/l sodium chloride solution, that neither the in utero period nor the postnatal, suckling period played a role in the development of the much larger total fluid intake (water plus saline) or saline preference (proportion of the total fluid intake taken as saline) of the SHR. We thus conclude that maternal and perinatal environmental factors do not play a major role in this behaviour and that the exaggerated saline preference of the SHR is probably largely genetically determined.

  2. Early high-sodium solid diet does not affect sodium intake, sodium preference, blood volume and blood pressure in adult Wistar-Kyoto rats.

    PubMed

    Ufnal, Marcin; Drapala, Adrian; Sikora, Mariusz; Zera, Tymoteusz

    2011-07-01

    A high-Na diet may lead to the development of hypertension in both humans and rats; however, the causes of Na intake in amounts greater than physiologically needed as well as the mechanisms whereby high-Na food elevates blood pressure are not clear. Therefore, we decided to test the hypothesis that a high-Na diet introduced after suckling affects Na intake, food preference, resting blood pressure and blood volume in adult rats. Male Wistar-Kyoto (WKY) rats, 4 weeks old, were divided into three groups and placed on either a high-Na (3.28%), a medium-Na (0.82%) or a regular diet (0.22%) with the same energy content for 8 weeks. Subsequently, food preference, resting arterial blood pressure, blood volume, plasma osmolality and Na blood level were evaluated. When offered a choice of diets, all the groups preferred the regular chow, and there was no significant difference in total Na intake between the groups. When the rats experienced the change from their initial chow to a new one with different Na content, they continued to eat the same amount of food. Body weight, resting arterial blood pressure, blood volume, plasma osmolality and Na blood level were comparable between the groups. In conclusion, the results show that a high-Na diet introduced immediately after suckling does not affect Na preference and Na intake in adult WKY rats. Furthermore, the findings provide evidence that both blood volume and arterial blood pressure are highly protected in normotensive rats on a high-Na diet.

  3. 17α-Oestradiol-induced neuroprotection in the brain of spontaneously hypertensive rats.

    PubMed

    Pietranera, L; Brocca, M E; Roig, P; Lima, A; Garcia-Segura, L M; De Nicola, A F

    2014-05-01

    17β-oestradiol is a powerful neuroprotective factor for the brain abnormalities of spontaneously hypertensive rats (SHR). 17α-Oestradiol, a nonfeminising isomer showing low affinity for oestrogen receptors, is also endowed with neuroprotective effects in vivo and in vitro. We therefore investigated whether treatment with 17α-oestradiol prevented pathological changes of the hippocampus and hypothalamus of SHR. We used 20-week-old male SHR with a blood pressure of approximately 170 mmHg receiving s.c. a single 800 μg pellet of 17α-oestradiol dissolved in cholesterol or vehicle only for 2 weeks Normotensive Wistar-Kyoto (WKY) rats were used as controls. 17α-Oestradiol did not modify blood pressure, serum prolactin, 17β-oestradiol levels or the weight of the testis and pituitary of SHR. In the brain, we analysed steroid effects on hippocampus Ki67+ proliferating cells, doublecortin (DCX) positive neuroblasts, glial fibrillary acidic protein (GFAP)+ astrocyte density, aromatase immunostaining and brain-derived neurotrophic factor (BDNF) mRNA. In the hypothalamus, we determined arginine vasopressin (AVP) mRNA. Treatment of SHR with 17α-oestradiol enhanced the number of Ki67+ in the subgranular zone and DCX+ cells in the inner granule cell layer of the dentate gyrus, increased BDNF mRNA in the CA1 region and gyrus dentatus, decreased GFAP+ astrogliosis in the CA1 subfield, and decreased hypothalamic AVP mRNA. Aromatase expression was unmodified. By contrast to SHR, normotensive WKY rats were unresponsive to 17α-oestradiol. These data indicate a role for 17α-oestradiol as a protective factor for the treatment of hypertensive encephalopathy. Furthermore, 17α-oestradiol is weakly oestrogenic in the periphery and can be used in males.

  4. 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

  5. Omapatrilat normalizes renal function curve in spontaneously hypertensive rats

    PubMed Central

    Morazo, Paloma; Fortepiani, Lourdes A; Clara Ortíz, M; Atucha, Noemí M; García-Estañ, Joaquín

    2001-01-01

    Background The present study was designed to analyze the chronic renal response to omapatrilat, a new vasopeptidase inhibitor, in spontaneously hypertensive rats (SHR). To that end, the renal and blood pressure response to a 4-day salt loading protocol was analyzed and the respective chronic renal curves constructed. Results In non treated animals, and under normal sodium intake (around 2 mEq/day), mean arterial pressure (MAP), was significantly higher in the SHR as compared with the controls (WKY). After increasing salt intake (8 times normal), MAP did not change significantly in any group and the animals reached a normal sodium balance in four days. In a second group of animals, omapatrilat was given orally for 15 days at the dose of 40 mg/kg/day in the drinking water. In these omapatrilat-treated animals, and under normal sodium intake, MAP was significantly lower in both groups, although the antihypertensive effect was much greater in the SHR, so that the MAP of the SHR group was completely normalized and similar to the WKY-treated group. The subsequent elevation of sodium intake did not significantly elevate MAP in any group and the animals could manage the sodium excess as well as the non treated groups. Conclusions These results indicate that chronic treatment with omapatrilat normalizes blood pressure in SHR without affecting adversely the renal ability to eliminate a sodium load. Chronic treatment with omapatrilat resets the chronic pressure natriuresis relationship of the SHR to a normal level, thus without altering the normal salt-independence of this arterial hypertension model. PMID:11592920

  6. 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.

  7. 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.

  8. DRL performance of spontaneously hypertensive rats: dissociation of timing and inhibition of responses.

    PubMed

    Orduña, Vladimir; Valencia-Torres, Lourdes; Bouzas, Arturo

    2009-07-19

    In this experiment, we used a differential reinforcement of low rates (DRL) schedule to evaluate the performance of spontaneously hypertensive rats (SHR), Wistar Kyoto (WKY) and Wistar (WIS) rats, with the goal of dissociating the processes of timing and inhibition of responses through the use of two quantitative models: the peak deviation analysis and the temporal regulation model. The subjects were divided in two groups; the first group was exposed to 70 sessions under a DRL 10s schedule. SHR rats showed an apparent temporary deficit in the inhibition of responses process; however, no differences among strains were observed in terms of the timing process. The second group of rats was exposed to 30 sessions in DRL 10s schedule, before receiving three doses (2 mg/kg, 4 mg/kg and 8 mg/kg) of methylphenidate. The results obtained through both models were consistent and indicated that at higher drug doses, the performance of all three strains of rats deteriorated. The impulsivity exhibited by SHR during acquisition supports the idea of these rats as an adequate animal model of ADHD. In contrast, evidence against this relies on the normal temporal processing found and in the worsening effect that methylphenidate produced in the process of inhibition of responses. These mixed results suggest the necessity of exploring timing behavior of other animal models in order to find a reliable animal model of ADHD.

  9. Potentiated response to adrenomedullin in myocardia and aortas in spontaneously hypertensive rat.

    PubMed

    Pan, Ch Shui; Jiang, W; Wu, Sh Ying; Zhao, J; Pang, Y Zheng; Tang, Ch Shu; Qi, Y Fen

    2006-05-01

    Adrenomedullin (AM) is a multifunctional regulatory peptide, and endogenous AM is an important factor in regulating cardiovascular and renal homeostasis as a potent cardio-reno-protective factor. To illustrate the protective mechanism of adrenomedullin (AM) on the cardiovascular system by observing (1) the changes in mRNA and protein levels of AM and its receptor-calcitonin receptor-like receptor (CL) and receptor activity-modifying proteins (RAMPs)-in myocardia and aortas of spontaneously hypertensive rats (SHRs) and (2) the response of cardiovascular tissue to AM. The AM content and cyclic adenosine monophosphate (cAMP) production in myocardia and aortas were measured in SHRs and Wistar Kyoto (WKY) rats (11-week-old) by radioimmunoassay (RIA). The mRNA levels of brain natriuretic peptide (BNP), AM, CL, RAMP1, -2, -3 were determined by semi-quantitative RTPCR. Protein levels of CL, RAMP1, -2, -3 were assayed by Western blotting. SHRs had severe hypertension, and the tail-blood pressure was 76.7% higher, the ratio of heart weight to body weight (heart coefficient) 45.5% higher, and the BNP gene expression 4.5-fold higher than that of WKY rats (all p < 0.01). The AM-ir content in plasma, myocardia and aortas of SHRs increased by 42.5%, 68.3% and 80.4%, respectively (all p < 0.01) compared with WKY rats. Furthermore, the mRNA levels of AM, CL, RAMP1, RAMP2 and RAMP3 were elevated by 46% (p < 0.01), 62% (p < 0.05), 51.2% (p < 0.01), 41% (p < 0.01) and 54% (p < 0.01), respectively, in myocardia and by 72%, 87%, 155%, 53% and 74% (all p < 0.01), respectively, in aortas. The elevated mRNA level of CL, RAMP1 RAMP2 and RAMP3 correlated positively with that of AM mRNA in hypertrophic myocardia (r= 0.943, 0.621, 0.688 and 0.633, respectively, all p < 0.01) and aortas (r = 0.762, 0.892, 0.828 and 0.736, respectively, all p < 0.01). The protein levels of CL, RAMP1, RAMP2 and RAMP3 in myocardia and aortas of SHRs were increased compared with that of WKY rats. The response to AM

  10. Enhanced expression of Cx43 and gap junction communication in vascular smooth muscle cells of spontaneously hypertensive rats

    PubMed Central

    Wang, Li-Jie; Liu, Wei-Dong; Zhang, Liang; Ma, Ke-Tao; Zhao, Lei; Shi, Wen-Yan; Zhang, Wen-Wen; Wang, Ying-Zi; Li, Li; Si, Jun-Qiang

    2016-01-01

    Niflumic acid (NFA) is a novel gap junction (GJ) inhibitor. The aim of the present study was to investigate the effect of NFA on GJ communication and the expression of connexin (Cx) in vascular smooth muscle cells (VSMCs) of mesenteric arterioles of spontaneously hypertensive rats (SHR). Whole-cell patch clamp recording demonstrated that NFA at 1×10–4 M significantly inhibited the inward current and its effect was reversible. The time for charging and discharging of cell membrane capacitance (Cinput) reduced from 9.73 to 0.48 ms (P<0.05; n=6). Pressure myograph measurement showed that NFA at 3×10-4 M fully neutralized the contraction caused by phenylephrine. The relaxation responses of normotensive control Wistar Kyoto (WKY) rats were significantly higher, compared with those of the SHRs (P<0.05; n=6). Western blot and reverse transcription-quantitative polymerase chain reaction analyses showed that the mRNA and protein expression levels of Cx43 of the third-level branch of mesenteric arterioles of the SHRs and WKY rats were higher, compared with those of the first-level branch. The mRNA and protein expression levels of Cx43 of the primary and third-level branches of the mesenteric arterioles in the SHRs were higher, compared with those in the WKY rats (P<0.05; n=6). The mRNA levels of Cx43 in the mesenteric arterioles were significantly downregulated by NFA in a concentration-dependent manner (P<0.01; n=6). The protein levels of Cx43 in primary cultured VSMCs isolated from the mesenteric arterioles were also significantly downregulated by NFA in a concentration-dependent manner (P<0.01; n=6). These results showed that the vasorelaxatory effects of GJ inhibitors were reduced in the SHRs, which was associated with a higher protein expression level of Cx43 in the mesenteric arterioles of the SHRs. NFA also relaxed the mesenteric arterioles by reducing the expression of Cx43, which decreased blood pressure. Therefore, regulation of the expression of GJs may be a

  11. Effects of kimchi supplementation on blood pressure and cardiac hypertrophy with varying sodium content in spontaneously hypertensive rats.

    PubMed

    Lee, Seung-Min; Cho, Yoonsu; Chung, Hye-Kyung; Shin, Dong-Hyuk; Ha, Woel-Kyu; Lee, Sang-Chul; Shin, Min-Jeong

    2012-08-01

    We tested the effects of dietary intake of freeze-dried Korean traditional fermented cabbage (generally known as kimchi) with varying amounts of sodium on blood pressure and cardiac hypertrophy in spontaneously hypertensive rats (SHRs). Wistar-Kyoto rats (WKY), as a control group, received a regular AIN-76 diet, and the SHRs were divided into four groups. The SHR group was fed a regular diet without kimchi supplementation, the SHR-L group was fed the regular diet supplemented with low sodium kimchi containing 1.4% salt by wet weight, which was provided in a freeze-dried form, the SHR-M group was supplemented with medium levels of sodium kimchi containing 2.4% salt, and the SHR-H group was supplemented with high sodium kimchi containing 3.0% salt. Blood pressure was measured over 6 weeks, and cardiac hypertrophy was examined by measuring heart and left ventricle weights and cardiac histology. SHRs showed higher blood pressure compared to that in WKY rats, which was further elevated by consuming high sodium containing kimchi but was not influenced by supplementing with low sodium kimchi. None of the SHR groups showed significant differences in cardiac and left ventricular mass or cardiomyocyte size. Levels of serum biochemical parameters, including blood urea nitrogen, creatinine, glutamic-oxaloacetic transaminase, glutamic-pyruvic transaminase, sodium, and potassium were not different among the groups. Elevations in serum levels of aldosterone in SHR rats decreased in the low sodium kimchi group. These results suggest that consuming low sodium kimchi may not adversely affect blood pressure and cardiac function even under a hypertensive condition.

  12. Inhibitory H3 receptors on sympathetic nerves of the pithed rat: activation by endogenous histamine and operation in spontaneously hypertensive rats.

    PubMed

    Godlewski, G; Malinowska, B; Buczko, W; Schlicker, E

    1997-02-01

    Our previous results demonstrate the occurrence of presynaptic inhibitory histamine H3 receptors on sympathetic neurons innervating resistance vessels of the pithed rat. The present study, in which new H3 receptor ligands with increased potency and selectivity (imetit, clobenpropit) were used, was designed to further explore the role of H3 receptors in the regulation of the rat cardiovascular system. In particular we were interested whether these receptors may be activated by endogenous histamine and whether they are detectable in an experimental model of hypertension. All experiments were performed on pithed and vagotomized rats treated with rauwolscine 1 mumol/kg. In normotensive Wistar rats the electrical (1 Hz, 1 ms, 50 V for 20 s) stimulation of the preganglionic sympathetic nerve fibres increased diastolic blood pressure by about 35 mmHg. Two H3 receptor agonists, R-(-)-alpha-methylhistamine and imetit, inhibited the electrically induced increase in diastolic blood pressure in a dose-dependent manner. The maximal effect (about 25%) was obtained for R-(-)-alpha-methylhistamine at about 10 mumol/kg and for imetit at about 1 mumol/kg. Two H3 receptor antagonists, thioperamide 1 mumol/kg and clobenpropit 0.1 mumol/kg, attenuated the inhibitory effect of imetit. The neurogenic vasopressor response was increased by about 15% by thioperamide 1 mumol/kg and clobenpropit 0.1 mumol/kg and decreased by 25% by the histamine methyltransferase inhibitor metoprine 37 mumol/kg. R-(-)-alpha-Methylhistamine, imetit, thioperamide, clobenpropit and metoprine did not affect the vasopressor response to exogenously added noradrenaline 0.01 mumol/kg (which increased diastolic blood pressure by about 40 mmHg). Metoprine had only a very low affinity for H3 binding sites (labelled by 3H-N alpha-methylhistamine; pKi 4.46). In pithed Wistar Kyoto (WKY) and spontaneously hypertensive (SHR) rats, electrical (1 Hz, 1 ms, 50 V for 10 s) stimulation increased diastolic blood pressure by 28

  13. 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.

  14. 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.

  15. Effect of age and methacholine on the rate and coronary flow of isolated hearts of diabetic rats.

    PubMed

    Li, X S; Tanz, R D; Chang, K S

    1989-08-01

    1. Isolated hearts perfused by the method of Langendorff from 6, 12 and 24 week streptozotocin (STZ) diabetic rats displayed a significant bradycardia following 60 min equilibration. The rate of hearts from 12-week diabetic rats (164 +/- 17) displayed the greatest bradycardia compared to age-matched controls (268 +/- 15; P less than 0.001), and diabetics treated with insulin (232 +/- 17; P less than 0.01), but by 52 weeks the heart rate of the 3 groups was similar. With advancing age the effect of STZ diabetes on the rate of rat isolated perfused hearts remained unchanged but the rate of the control and diabetic + insulin groups declined. 2. Hearts from 6-52 week STZ-treated rats were found to be more sensitive to the negative chronotropic effect of methacholine, the greatest difference occurring in hearts from the 12 week animals. Atropine (10(-7) M) did not affect the resting heart rate of age-matched controls or diabetics but blocked methacholine (2.6 x 10(-6) M)-induced bradycardia in both, suggesting that the site of action of diabetic bradycardia is not the muscarinic receptors. 3. At the end of equilibration there was a significant decrease in coronary flow in hearts from 12 week diabetic animals. In spontaneously beating diabetic rat hearts administration of methacholine (2.6 x 10(-6) M) produced a significantly greater decrease in coronary flow in the 12, 24 and 52 week diabetic hearts. When electrically paced (5 Hz) however, there was no difference in response to methacholine between the three groups except at 52 weeks between the age-matched control and diabetic groups. This suggests that the more pronounced reduction induced by methacholine on the coronary flow of diabetic hearts is secondary to its negative chronotropic effect. 4. In general, hearts from diabetic animals treated with insulin respond similarly to their agematched controls in the presence and absence of methacholine.

  16. Loss of Dnd1 facilitates the cultivation of genital ridge-derived rat embryonic germ cells.

    PubMed

    Northrup, Emily; Eisenblätter, Regina; Glage, Silke; Rudolph, Cornelia; Dorsch, Martina; Schlegelberger, Brigitte; Hedrich, Hans-Jürgen; Zschemisch, Nils-Holger

    2011-08-01

    Pluripotent cells referred to as embryonic germ cells (EGCs) can be derived from the embryonic precursors of the mature gametes: the primordial germ cells (PGCs). A homozygous mutation (ter) of the dead-end homolog 1 gene (Dnd1) in the rat causes gonadal teratocarcinogenesis and sterility due to neoplastic transformation and loss of germ cells. We mated heterozygous ter/+ WKY-Dnd1(ter)/Ztm rats and were able to cultivate the first genital ridge-derived EGCs of the rat embryo at day 14.5 post coitum (pc). Genotyping revealed that ten EGC lines were Dnd1 deficient, while only one wild type cell line had survived in culture. This suggests that the inactivation of the putative tumor suppressor gene Dnd1 facilitates the immortalization of late EGCs in vitro. Injection of the wild type EGCs into blastocysts resulted in the first germ-line competent chimeras. These new pluripotent rat EGCs offer an innovative approach for studies on germ cell tumor development as well as a new tool for genetic manipulations in rats.

  17. 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

  18. Adult Female Rats Altered Diurnal Locomotor Activity Pattern Following Chronic Methylphenidate Treatment

    PubMed Central

    Trinh, T.; Kohllepin, S; Yang, P.B.; Burau, K.D.; Dafny, N.

    2014-01-01

    Methylphenidate (MPD) is one of the most prescribed pharmacological agents and also used as cognitive enhancement and for recreational purposes. The objective of this study was to investigate the repetitive dose-response effects of MPD on rhythm locomotor activity pattern of female WKY rats and compare to prior study done on male. The hypothesis is that change in the circadian activity pattern indicates a long-lasting effect of the drug. Four animal groups (saline control, 0.6, 2.5, and 10.0 mg/kg MPD dose groups) were housed in a sound-controlled room at 12:12 light/dark cycle. All received saline injections on experimental day 1 (ED 1). On EDs 2-7, the control group received saline injection; the other groups received 0.6, 2.5, or 10.0 mg/kg MPD, respectively. On ED 8-10, injections were withheld. On ED 11, each group received the same dose as EDs 2-7. Hourly histograms and cosine statistical analyses calculating the acrophase (ϕ), amplitude (A), and MESOR (M) were applied to assess the 24-hour circadian activity pattern. The 0.6 and 2.5 mg/kg MPD groups exhibited significant (p<0.05) change in their circadian activity pattern on ED 11. The 10.0 mg/kg MPD group exhibited tolerance on ED 11 and also a significant change in activity pattern on ED 8 compared to ED 1, consistent with withdrawal behavior (p<0.007). In conclusion, chronic MPD administration alters circadian locomotor activity of adult female WKY rats and confirms that chronic MPD use elicits long lasting effects PMID:23893293

  19. Difference in effects of stretch on depressive effect of endothelium-derived nitric oxide on noradrenaline- and high-K+-induced contractions between the aortae from normotensive and spontaneously hypertensive rats.

    PubMed

    Sekiguchi, F; Miyake, Y; Nakazumi, S; Shimamura, K; Yamamoto, K; Sunano, S

    2001-02-01

    Difference in effects of stretch tension on endothelium-derived nitric oxide (EDNO)-dependent depression of noradrenaline (NA)- and high-K+-induced contraction between the aortae from normotensive Wistar Kyoto rats (WKY) a nd stroke-pronespontaneously hypertensive rats (SHRSP) was studied. NA-induced contraction in preparations both from WKY and SHRSP was augmented in the presence of N(omega)-nitro-L-arginine (L-NNA). This augmentation was minimized when the spontaneous tone, which was more prominent in preparations from SHRSP, was subtracted and the effects of L-NNA became less prominent in preparations from SHRSP. The effects of L-NNA were maximal at the stretch tension of 15 mN and, then, decreased as stretch tension increased in both preparations when the spontaneous tone was subtracted. The effects of L-NNA were less prominent when the contraction was initiated by high-K+, although the effects of stretch on high-K+-induced contraction were similar to that of NA-induced contraction. These results suggested 1) that both NA- and high-K+-induced contractions are depressed by EDNO, 2) that the release of EDNO induced by high-K+ is less than that by NA, 3) that increase in stretch tension decreases the release of EDNO, and 4) that the depressive effect of EDNO on contraction is impaired in the aorta of SHRSP.

  20. Polyphenol-containing azuki bean (Vigna angularis) seed coats attenuate vascular oxidative stress and inflammation in spontaneously hypertensive rats.

    PubMed

    Mukai, Yuuka; Sato, Shin

    2011-01-01

    We investigated the effects of azuki bean (Vigna angularis) seed coats (ABSC), which contain polyphenols, on the vascular oxidative stress and inflammation associated with hypertension. Spontaneously hypertensive rats (SHR) and control normotensive Wistar-Kyoto (WKY) rats were divided into 2 groups each. One group was fed 0% ABSC; the other, a 1.0% ABSC-containing diet. Tail systolic blood pressure (SBP) was examined throughout ABSC treatment. At 8 weeks, vascular superoxide (O(2)(-)) production was measured by lucigenin-enhanced chemiluminescence. mRNA expressions of nicotinamide adenine dinucleotide phosphate (NADPH) oxidase subunits, macrophage chemoattractant protein-1 (MCP-1) and its receptor C-C chemokine receptor 2 (CCR2) in the aorta were analyzed by reverse transcriptase-polymerase chain reaction. Protein expressions of inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2) were determined by western blotting. Polyphenol-containing ABSC suppressed the elevation of SBP throughout the treatment period. The NADPH-stimulated O(2)(-) level decreased significantly in the aorta of ABSC-treated SHR compared with the level of untreated SHR. The p47phox and Nox4 mRNA expression increased significantly in untreated SHR compared with that in WKY rats. Conversely, the level of p47phox mRNA was significantly lower in ABSC-treated SHR than in untreated SHR. The protein abundance of both iNOS and COX-2 was significantly decreased in the aorta of the ABSC-treated SHR compared with this abundance in untreated SHR. The MCP-1 and CCR2 mRNA expressions increased in untreated SHR, and these levels were significantly lower in ABSC-treated SHR. In conclusion, our results suggested that polyphenol-containing ABSC could attenuate vascular oxidative stress and inflammation during the progression of hypertension, and this may lead to an improvement in hypertension.

  1. Effects of serotonin-norepinephrine reuptake inhibitors on locomotion and prefrontal monoamine release in spontaneously hypertensive rats.

    PubMed

    Umehara, Masato; Ago, Yukio; Fujita, Kazumi; Hiramatsu, Naoki; Takuma, Kazuhiro; Matsuda, Toshio

    2013-02-28

    Catecholamine neurotransmission in the prefrontal cortex plays a key role in the therapeutic actions of drugs for attention-deficit/hyperactivity disorder (ADHD). Recent clinical studies show that several serotonin-norepinephrine reuptake inhibitors have potential for treating ADHD. In this study, we examined the effects of acute treatment with serotonin-norepinephrine reuptake inhibitors on locomotion and the extracellular levels of monoamines in the prefrontal cortex in spontaneously hypertensive rats (SHR), an animal model of ADHD. Adolescent male SHR exhibited greater horizontal locomotion in an open-field test than male WKY control rats. Psychostimulant methylphenidate (0.3 and 1 mg/kg), the selective norepinephrine reuptake inhibitor atomoxetine (1 and 3 mg/kg), and serotonin-norepinephrine reuptake inhibitors duloxetine (10 mg/kg), venlafaxine (10 and 30 mg/kg) and milnacipran (30 mg/kg) reduced the horizontal activity in SHR, but did not affect in WKY rats. The selective norepinephrine reuptake inhibitor reboxetine (10 mg/kg) and the tricyclic antidepressant desipramine (10 and 30 mg/kg) also reduced the horizontal activity in SHR, whereas the selective serotonin reuptake inhibitor citalopram (30 mg/kg) did not. Microdialysis studies showed that atomoxetine, methylphenidate, duloxetine, venlafaxine, milnacipran, and reboxetine increased the extracellular levels of norepinephrine and dopamine in the prefrontal cortex in SHR. Citalopram did not affect norepinephrine and dopamine levels in the prefrontal cortex, although it increased the serotonin levels. Neither duloxetine nor venlafaxine increased the dopamine levels in the striatum. These findings suggest that serotonin-norepinephrine reuptake inhibitors, similar to methylphenidate and atomoxetine, have potential for ameliorating motor abnormality in the SHR model.

  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. Different relations between schedule-induced polydipsia and impulsive behaviour in the Spontaneously Hypertensive Rat and in high impulsive Wistar rats: questioning the role of impulsivity in adjunctive behaviour.

    PubMed

    Ibias, Javier; Pellón, Ricardo

    2014-09-01

    Rats belonging to three different strains (15 Wistar, 8 Spontaneously Hypertensive - SHR- and 8 Wistar Kyoto - WKY-) were used to evaluate the possible relationship between different levels of impulsivity and development of schedule-induced polydipsia (SIP). We first measured the rats' levels of impulsivity by means of delay-discounting and indifference-point procedures. Secondly, development of SIP was studied under a series of fixed time 15, 30, 60 and 120s food schedules, which were counterbalanced by means of a Latin-square design. Finally, we re-assessed the rats' levels of impulsivity by replicating the delay-discounting test. The findings showed that, starting from equivalent levels of impulsivity, development of SIP differed among the groups of rats. In comparison with the rest of the animals, the SHRs were observed to attain elevated drinking rates under SIP. On the other hand, the Wistar rats which had initial high impulsivity levels similar to those of the SHRs, displayed the lowest rates of induced drinking. Moreover, low levels of impulsivity in Wistar rats prior to SIP acquisition were reflected into high drinking rates. Relation of SIP and impulsivity is questioned by present results, which gives ground to the understanding of the behavioural mechanisms involved in adjunctive behaviour and its usefulness as an animal model of excessive behaviour.

  4. HIV-1 transgenic rats display alterations in immunophenotype and cellular responses associated with aging.

    PubMed

    Abbondanzo, Susan J; Chang, Sulie L

    2014-01-01

    Advances in anti-retroviral therapy over the last two decades have allowed life expectancy in patients infected with the human immunodeficiency virus to approach that of the general population. The process of aging in mammalian species, including rats, results in immune response changes, alterations in immunological phenotypes, and ultimately increased susceptibility to many infectious diseases. In order to investigate the immunological pathologies associated with chronic HIV-1 disease, particularly in aging individuals, the HIV-1 transgenic (HIV-1Tg) rat model was utilized. HIV-1Tg rats were challenged with lipopolysaccharide (LPS) to determine immunological alterations during the aging process. LPS is known to cause an imbalance in cytokine and chemokine release, and provides a method to identify changes in immune responses to bacterial infection in an HIV animal model. An immune profile and accompanying cellular consequences as well as changes in inflammatory cytokine and chemokine release related to age and genotype were assessed in HIV-1Tg rats. The percentage of T cells decreased with age, particularly T cytotoxic cells, whereas T helper cells increased with age. Neutrophils and monocytes increased in HIV-1Tg rats during maturation compared to age-matched F344 control rats. Aging HIV-1Tg rats displayed a significant increase in the pro-inflammatory cytokines, IL-6 and TNF-α, along with an increase in the chemokine, KC/GRO, in comparison to age-matched controls. Our data indicate that immunophenotype and immune responses can change during aging in HIV-positive individuals. This information could be important in determining the most beneficial age-dependent therapeutic treatment for HIV patients.

  5. 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

  6. 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.

  7. Changes of imidazoline receptors in spontaneously hypertensive rats

    PubMed Central

    Mar, Guang-Yuan; Chou, Ming-Ting; Chung, Hsien-Hui; Chiu, Nien-Hua; Chen, Mei-Fen; Cheng, Juei-Tang

    2013-01-01

    The role of imidazoline receptors in the regulation of vascular function remains unclear. In this study, we evaluated the effect of agmatine, an imidazoline receptor agonist, on systolic blood pressure (SBP) in spontaneously hypertensive rats (SHRs) and investigated the expressions of imidazoline receptors by Western blot. The isometric tension of aortic rings isolated from male SHRs was also estimated. Agmatine decreased SBP in a dose-dependent manner in SHRs but not in the normal group [Wistar–Kyoto (WKY) rats]. This reduction in SBP in SHRs was abolished by BU224, a selective antagonist of imidazoline I2-receptors. Higher expression of imidazoline receptors in SHR was observed. Moreover, agmatine-induced relaxation in isolated aortic rings precontracted with phenylephrine or KCl. This relaxation was also abolished by BU224 but was not modified by efaroxan, an imidazoline I1-receptor antagonist. Agmatine-induced relaxation was also attenuated by PNU 37883, a selective blocker of vascular ATP-sensitive potassium (KATP) channels. Additionally, vasodilatation by agmatine was reduced by an inhibitor of protein kinase A (PKA). We suggest that agmatine can lower blood pressure in SHRs through activation of the peripheral imidazoline I2-receptor, which is expressed more highly in SHRs. PMID:23176371

  8. Transition from compensatory hypertrophy to dilated, failing left ventricles in Dahl salt-sensitive rats.

    PubMed

    Inoko, M; Kihara, Y; Morii, I; Fujiwara, H; Sasayama, S

    1994-12-01

    To establish an experimental model for studying a specific transitional stage for compensatory hypertrophy to heart failure, we studied the pathophysiology of the left ventricle (LV) in Dahl salt-sensitive (DS) rats fed a high-salt diet. DS rats fed an 8% NaCl diet after the age of 6 wk developed concentric LV hypertrophy at 11 wk, followed by marked LV dilatation at 15-20 wk. During the latter stage, the DS rats showed labored respiration with LV global hypokinesis. All the DS rats died within 1 wk by massive pulmonary congestion. The dissected left ventricles revealed chamber dilatation and a marked increase in mass without myocardial necrosis. In contrast, corresponding Dahl salt-resistant (DR) rats fed the same diet showed neither mortality nor any of these pathological changes. The in vivo LV end-systolic pressure-volume relationship shifted to the right with a less steep slope in the failing DS rats compared with that in age-matched DR rats. Isometric contractions of LV papillary muscles isolated from these DS rats showed reduced tension development in the failing stage, but normal tension development in the hypertrophied stage. In conclusion, the DS rat fed a high-salt diet is a useful model showing rapidly developing congestive heart failure, in which the transition from compensatory hypertrophy to decompensatory dilatation of LV is easily and consistently manifested.

  9. Alternate cadmium exposure differentially affects the content of gamma-aminobutyric acid (GABA) and taurine within the hypothalamus, median eminence, striatum and prefrontal cortex of male rats.

    PubMed

    Esquifino, A I; Seara, R; Fernández-Rey, E; Lafuente, A

    2001-05-01

    This work examines changes of gamma aminobutyric acid (GABA) and taurine contents in the hypothalamus, striatum and prefrontal cortex of the rat after an alternate schedule of cadmium administration. Age-associated changes were also evaluated, of those before puberty and after adult age. In control rats GABA content decreased with age in the median eminence and in anterior, mediobasal and posterior hypothalamus, prefrontal cortex and the striatum. Taurine content showed similar results with the exception of mediobasal hypothalamus and striatum, where no changes were detected. In pubertal rats treated with cadmium from 30 to 60 days of life, GABA content significantly decreased in all brain regions except in the striatum. When cadmium was administered from day 60 to 90 of life, GABA content was significantly changed in prefrontal cortex only compared with the age matched controls. Taurine content showed similar results in pubertal rats, with the exception of the median eminence and the mediobasal hypothalamus, neither of which showed a change. However, when cadmium was administered to rats from day 60 to 90 of life, taurine content only changed in prefrontal cortex compared with the age matched controls. These results suggest that cadmium differentially affects GABA and taurine contents within the hypothalamus, median eminence, striatum and prefrontal cortex as a function of age.

  10. 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.

  11. Chronic enalapril treatment increases transient outward potassium current in cardiomyocytes isolated from right ventricle of spontaneously hypertensive rats.

    PubMed

    Rodrigues Junior, Luiz Fernando; de Azevedo Carvalho, Ana Carolina; Pimentel, Enildo Broetto; Mill, José Geraldo; Nascimento, José Hamilton Matheus

    2017-03-01

    It has been well established that chronic pressure overload resulting from hypertension leads to ventricular hypertrophy and electrophysiological remodeling. The transient outward potassium current (I to) reduction described in hypertensive animals delays ventricular repolarization, leading to complex ventricular arrhythmias and sudden death. Antihypertensive drugs, as angiotensin-converting enzyme inhibitors (ACEi), can restore I to and reduce the incidence of arrhythmic events. The purpose of this study was to evaluate the differential effects of long-term treatment with ACEi or direct-acting smooth muscle relaxant on the I to of left and right ventricle myocytes of spontaneously hypertensive rats (SHR). Animals were divided into four groups: normotensive Wistar-Kyoto rats (WKY), hypertensive (SHR), SHR treated for 6 weeks with enalapril 10 mg/kg/day (SHRE), or hydralazine 20 mg/kg/day (SHRH). Systolic blood pressure (SBP) and hypertrophy index (heart weight/body weight (HW/BW)) were determined at the end of treatment period. Cell membrane capacitance (C m) and I to were assessed in cardiomyocytes isolated from left and right ventricles. The SHR exhibited significantly increased SBP and HW/BW when compared to the WKY. The treated groups, SHRE and SHRH, restored normal SBP but not HW/BW. The SHR group exhibited a diminished I to in the left but not the right ventricle. Both the treated groups restored I to in the left ventricle. However, in the right ventricle, only enalapril treatment modified I to. The SHRE group exhibited a significant increase in I to compared to all the other groups. These findings suggest that enalapril may increase I to by a pressure overload independent mechanism.

  12. Effect of losartan with folic acid on plasma homocysteine and vascular ultrastructural changes in spontaneously hypertensive rats.

    PubMed

    Zhu, Lihe; Yu, Jiong; Jia, Baofu; Zhao, Feng; Tang, Mengmeng; Hu, Lufeng; Lin, Feiyan

    2015-01-01

    Elevated homocysteine (Hcy) is a high risk factor of hypertension due to its function in endothelial dysfunction. Its level in the blood is strongly influenced by folic acid. In order to investigate the effects of losartan with folic acid on plasma level of Hcy and vascular ultrastructural changes, thirty spontaneously hypertensive rats (SHR) involved and randomly divided into three groups (n=10): SHR-C group (control), SHR-L group (losartan 25 mg · kg(-1) · d(-1)), SHR-L+Y group (losartan 25 mg · kg(-1) · d(-1) + folic acid 0.4 mg · kg(-1) · d(-1)). Another 10 Wistar Rats involved as WKY-C group for normal control. The level of plasma Hcy was measured dynamically by LS-MS, the vascular ultrastructural changes were analyzed by light and electron microscopy. Moreover, the thickness and area of aorta was measured. The results showed the Hcy levels in four groups were WKY-C 7.49 ± 1.95 μmol/L; SHR-C 8.45 ± 1.90 μmol/L; SHR-L 8.28 ± 2.11 μmol/L; SHR-L+Y 7.53 ± 2.02 μmol/L at 80 days. There was no significant change for plasma Hcy (P>0.05). The morphological change showed the subendothelial space didn't increased significantly, the endothelial cells have a more smooth and intact cellular membrane in SHR-L+Y group. In conclusion, Losartan combined with folic acid could improve arterial endothelial structure in SHR which has no significant correlation with plasma Hcy.

  13. Effect of 2'-phosphophloretin on renal function in chronic renal failure rats.

    PubMed

    Peerce, B E; Weaver, L; Clarke, R D

    2004-07-01

    Hyperhosphatemia and secondary hyperparathyroidism are common and severe complications of chronic renal failure. Therapies to reduce serum phosphate have been shown to reduce serum parathyroid hormone (PTH) and slow the progression of renal failure. The effect of the inhibitor of intestinal phosphate absorption, 2'-phosphophloretin (2'-PP), on serum and urine chemistry, renal histology, and cardiac structure in the uremic rat model of renal failure, 5/6 nephrectomy (5/6 NX), was examined. The effect of 2'-PP on serum phosphate, serum PTH, serum total Ca(2+), and ionized Ca(2+), Ca(2+) x P(i) product, urine protein, urine osmolality, and creatinine clearance in 5/6 NX rats was examined. Uremic rats in chronic renal failure were gavaged daily with 25 microM 2'-PP. Over the course of a 5-wk experiment, serum chemistry in untreated uremic rats, 2'-PP-treated uremic rats, and age-matched control rats with normal renal function was determined twice a week. Urine creatinine, urine osmolality, urine phosphate, and urine protein were determined once a week from 24-h collections. 2'-PP reduced serum phosphate 40 +/- 3% compared with a 17% increase in untreated uremic control rats. 2'-PP did not alter total serum Ca(2+). During 5-wk experiments, serum PTH increased 65 +/- 25% in untreated uremic rats and decreased 70 +/- 7% in uremic rats treated with 25 microM 2'-PP. Creatinine clearance decreased 20% in untreated uremic rats compared with a 100% increase in 2'-PP-treated uremic rats. Urine protein decreased and urine osmolality increased in uremic rats treated with 2'-PP. The mechanism of the effect of 2'-PP on serum phosphate was inhibition of intestinal phosphate absorption. 2-PP inhibited intestinal phosphate absorption 50% without altering dietary protein absorption or intestinal Ca(2+) absorption. Over the course of the 5-wk treatment with 2'-PP, uremic animals treated with 2'-PP had a 2-4% weight gain/wk, similar to the weight gain seen in age-matched control rats

  14. Metabolomic study on the antihypertensive effect of S-1-propenylcysteine in spontaneously hypertensive rats using liquid chromatography coupled with quadrupole-Orbitrap mass spectrometry.

    PubMed

    Matsutomo, Toshiaki; Ushijima, Mitsuyasu; Kodera, Yukihiro; Nakamoto, Masashi; Takashima, Miyuki; Morihara, Naoaki; Tamura, Koichi

    2017-03-01

    Aged garlic extract (AGE) has been shown to improve hypertension in both clinical trials and experimental animal models. However, the active ingredient of AGE remains unknown. In the present study, we investigated the antihypertensive effects of AGE and its major constituents including S-1-propenylcysteine (S1PC) and S-allylcysteine (SAC) using spontaneously hypertensive rats (SHR) and found that S1PC is an active substance to lower blood pressure in SHR. In addition, the metabolomics approach was used to investigate the potential mechanism of the antihypertensive action of S1PC in SHR. Treatment with AGE (2g/kg body weight) or S1PC (6.5mg/kg body weight; equivalent to AGE 2g/kg body weight) significantly decreased the systolic blood pressure (SBP) of SHR after the repeated administration for 10 weeks, whereas treatment with SAC (7.9mg/kg body weight; equivalent to AGE 2g/kg body weight) did not decrease the SBP. After the treatment for 10 weeks, the plasma samples obtained from Wistar Kyoto (WKY) rats and SHR were analyzed by means of ultra high performance liquid chromatography coupled with high-resolution quadrupole-Orbitrap mass spectrometry. Multivariate statistical analysis of LC-MS data showed a clear difference in the metabolite profiles between WKY rats and SHR. The results indicated that 30 endogenous metabolites significantly contributed to the difference and 7 of 30 metabolites were changed by the S1PC treatment. Furthermore, regression analysis showed correlation between SBP and the plasma levels of betaine, tryptophan and 3 LysoPCs. This metabolomics approach suggested that S1PC could exert its antihypertensive effect by affecting glycine, serine and threonine metabolism, tryptophan metabolism and glycerophospholipid metabolism.

  15. Sex-and lineage-specific inheritance of depression-like behavior in the rat

    PubMed Central

    Solberg, Leah C.; Baum, Amber E.; Ahmadiyeh, Nasim; Shimomura, Kazuhiro; Li, Renhua; Turek, Fred W.; Churchil, Gary A.; Takahashi, Joseph S.; Redei, Eva E.

    2013-01-01

    The Wistar–Kyoto (WKY) rat exhibits physiological and behavioral similarities to endophenotypes of human depression. In the forced swim test (FST), a wel-characterized antidepressant-reversible test for behavioral despair in rodents, WKYs express characteristics of behavioral despair; increased immobility, and decreased climbing. To map genetic loci linked to behavior in the FST, we conducted a quantitative trait loci (QTL) analysis of the segregating F2 generation of a WKY · Fisher 344 (F344) reciprocal intercross. Using linear-model-based genome scans to include covariate (sex or lineage) by-QTL interaction effects, four significant QTL influencing climbing behavior were identified. In addition, we identified three, seven, and two suggestive QTL for climbing, immobility, and swimming, respectively. One of these loci was pleiotropic, affecting both immobility and climbing. As found in human linkage studies, several of these QTL showed sex-and/or lineage-dependent effects. A simultaneous search strategy identified three epistatic locus pairs for climbing. Multiple regression analysis was employed to characterize the joint contributions of these QTL and to clarify the sex-and lineage-dependent effects. As expected for complex traits, FST behavior is influenced by multiple QTL of smal effect, each contributing 5%–10%, accounting for a total 10%–30% of the phenotypic variance. A number of loci mapped in this study share overlapping candidate regions with previously identified emotionality QTL in mice as wel as with susceptibility loci recognized by linkage or genome scan analyses for major depression or bipolar disorder in humans. The presence of these loci across species suggests that these QTL may represent universal genetic factors contributing to mood disorders. PMID:15457344

  16. Sex- and lineage-specific inheritance of depression-like behavior in the rat.

    PubMed

    Solberg, Leah C; Baum, Amber E; Ahmadiyeh, Nasim; Shimomura, Kazuhiro; Li, Renhua; Turek, Fred W; Churchill, Gary A; Takahashi, Joseph S; Redei, Eva E

    2004-08-01

    The Wistar-Kyoto (WKY) rat exhibits physiological and behavioral similarities to endophenotypes of human depression. In the forced swim test (FST), a well-characterized antidepressant-reversible test for behavioral despair in rodents, WKYs express characteristics of behavioral despair; increased immobility, and decreased climbing. To map genetic loci linked to behavior in the FST, we conducted a quantitative trait loci (QTL) analysis of the segregating F2 generation of a WKY x Fisher 344 (F344) reciprocal intercross. Using linear-model-based genome scans to include covariate (sex or lineage)-by-QTL interaction effects, four significant QTL influencing climbing behavior were identified. In addition, we identified three, seven, and two suggestive QTL for climbing, immobility, and swimming, respectively. One of these loci was pleiotropic, affecting both immobility and climbing. As found in human linkage studies, several of these QTL showed sex- and/or lineage-dependent effects. A simultaneous search strategy identified three epistatic locus pairs for climbing. Multiple regression analysis was employed to characterize the joint contributions of these QTL and to clarify the sex- and lineage-dependent effects. As expected for complex traits, FST behavior is influenced by multiple QTL of small effect, each contributing 5%-10%, accounting for a total 10%-30% of the phenotypic variance. A number of loci mapped in this study share overlapping candidate regions with previously identified emotionality QTL in mice as well as with susceptibility loci recognized by linkage or genome scan analyses for major depression or bipolar disorder in humans. The presence of these loci across species suggests that these QTL may represent universal genetic factors contributing to mood disorders.

  17. 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.

  18. 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

  19. Effects of perinatal undernutrition on elimination of immature myosin isoforms in the rat diaphragm.

    PubMed

    Brozanski, B S; Daood, M J; LaFramboise, W A; Watchko, J F; Foley, T P; Butler-Browne, G S; Whalen, R G; Guthrie, R D; Ontell, M

    1991-08-01

    The effect of perinatal undernutrition on the postnatal elimination of immature myosin isoforms in rat diaphragm muscle was examined using electrophoretic and immunocytochemical techniques. Electrophoresis of native myosin showed that neonatal bands were present in diaphragm muscles of both control and undernourished rats on day 4. By day 21, the neonatal bands were diminished in the control diaphragm compared with the diaphragm of the undernourished rats. Neonatal bands persisted on postnatal day 30 in the diaphragm of the undernourished rats but not in the diaphragm of control rats. No significant difference in the time course of elimination of embryonic myosin light chain (LCemb) was observed between the diaphragm muscles of control and undernourished rats with two-dimensional gel electrophoresis. Immunocytochemical analysis demonstrated embryonic myosin heavy chain (MHCemb) in all myofibers of the diaphragm muscle of both groups at day 4, but this isoform was not detected in either group by day 14. Reactivity with anti-neonatal myosin heavy chain (MHCneo) indicated that rate of elimination of the MHCneo was delayed in the undernourished state as compared with the normal rats (P less than 0.001). Serum triiodothyronine levels were measured at 14, 21, and 30 days and were significantly lower in the undernourished rats compared with age-matched controls. These data demonstrate that the normal postnatal decrease in MHCneo, but not MHCemb or LCemb, is affected by the nutritional state of the animal. We speculate that these alterations in myosin isoform transitions are induced by hypothyroidism associated with undernutrition.

  20. The dipeptidyl peptidase-4 inhibitor teneligliptin improved endothelial dysfunction and insulin resistance in the SHR/NDmcr-cp rat model of metabolic syndrome.

    PubMed

    Nakagami, Hironori; Pang, Zhengda; Shimosato, Takashi; Moritani, Toshinori; Kurinami, Hitomi; Koriyama, Hiroshi; Tenma, Akiko; Shimamura, Munehisa; Morishita, Ryuichi

    2014-07-01

    Diabetes mellitus, hypertension and metabolic syndrome are major risk factors for the occurrence of cardiovascular events. In this study, we used spontaneous hypertensive rat (SHR)/NDmcr-cp (cp/cp) (SHRcp) rats as a model for metabolic syndrome to examine the effects of dipeptidyl peptidase (DPP)-4 inhibition on hypertension, glucose metabolism and endothelial dysfunction. First, we confirmed that SHRcp rats showed very severe obesity, hypertension and endothelial dysfunction phenotypes from 14 to 54 weeks of age. Next, we examined whether the DPP-4 inhibitor teneligliptin (10 mg kg(-1) per day per os for 12 weeks) could modify any of these phenotypes. Treatment with teneligliptin significantly improved hyperglycemia and insulin resistance, as evidenced by an oral glucose tolerance test and homeostasis model assessment for insulin resistance, respectively. Teneligliptin showed no effects on systolic blood pressure or heart rate. In regard to endothelial function, the vasodilator response to acetylcholine was significantly impaired in SHRcp rats when compared with WKY rats. Long-term treatment with teneligliptin significantly attenuated endothelial dysfunction through the upregulation of endothelium-derived nitric oxide synthase mRNA. These results demonstrate that long-term treatment with teneligliptin significantly improved endothelial dysfunction and glucose metabolism in a rat model of metabolic syndrome, suggesting that teneligliptin treatment might be beneficial for patients with hypertension and/or diabetes.

  1. 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.

  2. Postnatal growth hormone deficiency in growing rats causes marked decline in the activity of spinal cord acetylcholinesterase but not butyrylcholinesterase.

    PubMed

    Koohestani, Faezeh; Brown, Chester M; Meisami, Esmail

    2012-11-01

    The effects of growth hormone (GH) deficiency on the developmental changes in the abundance and activity of cholinesterase enzymes were studied in the developing spinal cord (SC) of postnatal rats by measuring the specific activity of acetylcholinesterase (AChE), a marker for cholinergic neurons and their synaptic compartments, and butyrylcholinesterase (BuChE), a marker for glial cells and neurovascular cells. Specific activities of these two enzymes were measured in SC tissue of 21- and 90 day-old (P21, weaning age; P90, young adulthood) GH deficient spontaneous dwarf (SpDwf) mutant rats which lack anterior pituitary and circulating plasma GH, and were compared with SC tissue of normal age-matched control animals. Assays were carried out for AChE and BuChE activity in the presence of their specific chemical inhibitors, BW284C51 and iso-OMPA, respectively. Results revealed that mean AChE activity was markedly and significantly reduced [28% at P21, 49% at P90, (p<0.01)] in the SC of GH deficient rats compared to age-matched controls. GH deficiency had a higher and more significant effect on AChE activity of the older (P90) rats than the younger ones (P21) ones. In contrast, BuChE activity in SC showed no significant changes in GH deficient rats at either of the two ages studied. Results imply that, in the absence of pituitary GH, the postnatal proliferation of cholinergic synapses in the rat SC, a CNS structure, where AChE activity is abundant, is markedly reduced during both the pre- and postweaning periods; more so in the postweaning than preweaning ages. In contrast, the absence of any effects on BuChE activity implies that GH does not affect the development of non-neuronal elements, e.g., glia, as much as the neuronal and synaptic compartments of the developing rat SC.

  3. Early Vaginal Opening in Juvenile Female Rats Given BRAF-Inhibitor Dabrafenib Is Not Associated with Early Physiologic Sexual Maturation.

    PubMed

    Posobiec, Lorraine M; Vidal, Justin D; Hughes-Earle, Angela; Laffan, Susan B; Hart, Timothy

    2015-12-01

    Dabrafenib (DAB), an inhibitor of BRAF kinase activity, is approved for metastatic melanoma with a BRAF V600E mutation. In support of pediatric cancer development, a nonclinical juvenile rat toxicity study was conducted in which females had early vaginal opening (VO). It was hypothesized that the early VO was not indicative of sexual maturation, but a result of a local effect on the vagina. An investigative study was conducted that mimicked the definitive study design, with rats given DAB or vehicle orally from Postnatal Day (PND) 7 to 35 and with necropsy subsets just before VO, at the first and second estrus, along with age-matched controls. Histopathology was performed on reproductive tissues, including immunohistochemistry for BRAF expression. VO occurred earlier in DAB females than in controls (PND 27.2 vs. 31.5); however, the timing of the first estrus was unaffected (PND 34.0 vs. 33.0). DAB-treated females evaluated just before VO (PND 22.0) had mostly immature reproductive tracts with no evidence of ovulation, similar to age-matched controls; however, DAB-treated females had keratinized and histologically open vaginas. Also, there was raised skin around the urogenital area, which correlated with hyperplasia/keratosis of the vulvar skin and keratinization of the distal vagina. BRAF expression (evaluated in controls) was localized to these tissues. Thus, early VO in rats given DAB likely represents a local effect accelerating vaginal keratinization to become open and not accelerated sexual maturation.

  4. 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.

  5. Lectin histochemistry and alkaline phosphatase activity in the pia mater vessels of spontaneously hypertensive rats (SHR).

    PubMed

    Szumańska, G; Gadamski, R

    1992-01-01

    Some lectins were used to study the localization of sugar residues on the endothelial cell surface in the pia mater blood vessels of control (WKY) and hypertensive rats (SHR). The lectins tested recognized the following residues: beta-D-galactosyl (Ricinus communis agglutinin 120, RCA-1), alpha-L-fucosyl (Ulex europaeus agglutinin, UEA-1), N-acetylglucosaminyl and sialyl (Wheat germ agglutinin, WGA), N-glycolyl-neuraminic acid (Limax flavus agglutinin, LFA), and N-acetyl-D-galactosaminyl (Helix pomatia agglutinin, HPA). Several differences were revealed in the presence of sugar receptors on the surface of endothelial cells between the control and the hypertensive rats. Our studies showed also differences in the localization of the tested glycoconjugates between pial capillaries, small, medium-size and large pial arteries. The histochemical evaluation of alkaline phosphatase revealed an increased activity of the enzyme in the pial vessels of SHRs as compared with control rats with a similar localization of the enzyme activity. Some differences in the distribution of lectin binding sites and alkaline phosphatase activity could be associated with the different functions of particular segments of the pial vascular network.

  6. Establishment and use of the M strain of stroke-prone spontaneously hypertensive rat.

    PubMed

    Okamoto, K; Yamamoto, K; Morita, N; Ohta, Y; Chikugo, T; Higashizawa, T; Suzuki, T

    1986-10-01

    An inbred strain of stroke-prone spontaneously hypertensive rat, the M-SHRSP, was established by brother-sister breeding of selected SHRSP for 24 generations while administering apresoline. Compared with SHRSP, the M-SHRSP shows an earlier rise in blood pressure, plasma renin activity (PRA) and cerebrospinal fluid (CSF) pressure, and somewhat changed cerebrovascular lesions. Crosses and back-crosses, using M-SHRSP, Wistar-Kyoto rats (WKY), spontaneously hypercholesterolaemic (SHC) rats and their hybrids produced colonies with various blood pressure levels and hypercholesterolaemia. Continued successive selective brother-sister breeding of M-SHRSP and SHC hybrids produced a colony with severe hypertension and marked hypercholesterolaemia. Streptozotocin diabetes was induced in an M-SHRSP and SHC hybrid (TC), from which diabetic TC was successively bred to the fifth generation. While each generation was hypertensive and showed a decrease in islet B-cells, symptoms of lasting glycosuria were first observed in the fourth generation among those given a high alpha-corn starch (75.7%) diet.

  7. Preventive Effect of Carvacrol Against Oxidative Damage in Aged Rat Liver.

    PubMed

    Samarghandian, Saeed; Azimi-Nezhad, Mohsen; Farkhondeh, Tahereh

    2016-11-21

    The present study was designed to investigate the changes in activities of antioxidant enzymes and lipid peroxidation level in the liver of 2, 10 and 20 months old rats, and to see whether these changes are restored to those of the two month old rats after carvacrol treatment. Male rats of 2, 10, and 20 months (n = 10 for each group) were used for all the experiments. The aged rats (10 and 20 months old) were given carvacrol (15 mg/day per body weight) for 30 days. Control animals received an equal volume of vehicle. After the treatment, livers were removed for estimation of superoxide dismutase-SOD, glutathione-S-transferase-GST, catalase-CAT activities and lipid peroxidation level. The present findings determined that normal aging was associated with a significant decrease in the activities of antioxidant enzymes (SOD; 11.87 ± 0.6 (2 months old) vs 7.56 ± 0.1 (20 months old); P < 0.001) in liver, as well as an increase in lipid peroxidation level (MDA; 0.15 ± 0.01 (2 months old) vs 0.41 ± 0.01 (20 months old); P < 0.001) in aged rats. Also, the results of this study indicated that carvacrol treatment increased the activities of the antioxidant enzymes in 20 months old animals versus the aged matched control group (SOD; 9.87 ± 0.4; P < 0.01). Furthermore, carvacrol decreased lipid peroxidation content in 10 and 20 months old animals compared with the aged matched control (MDA; 9.87 ± 0.4; P < 0.001). Our data shows that carvacrol could be a candidate to inhibit the development of age-induced liver damage through inhibition of oxidative stress and also increasing antioxidant defenses.

  8. Mechanism of Impaired Water Excretion in the Hypothyroid Rat

    PubMed Central

    Emmanouel, Dimitrios S.; Lindheimer, Marshall D.; Katz, Adrian I.

    1974-01-01

    The ability to excrete an oral water load and the renal diluting mechanism were studied in hypothyroid rats and in age-matched euthyroid controls. Hypothyroid animals excreted a significantly smaller fraction of a 50-ml/kg oral water load than controls, demonstrating the same limited ability to excrete free water as thyroid-deficient man. During hypotonic (0.45%) saline infusion, absolute sodium delivery to the diluting segment and free water clearance were markedly lower in hypothyroid rats. However, both fractional distal sodium delivery and fractional free water clearance were similar in hypothyroid and control animals, suggesting that the reduced absolute free water formation in hypothyroid rats was due to decreased net distal delivery. In support of this hypothesis was the observation that fractional distal sodium reabsorption was equal or higher in thyroid-deficient rats, which indicates that the sodium reabsorptive capacity of the diluting segment was preserved in these animals. The results cannot be attributed to incomplete suppression of antidiuretic hormone (ADH) since they were identical in diabetes insipidus rats, nor to different rates of non-ADH-dependent backflux of filtrate since tissue osmolality and solute concentrations in the cortex, medulla, and papilla were similar in hypothyroid and control rats of both Sprague-Dawley and Brattleboro strains. The functional integrity of the diluting segment in hypothyroid rats was further demonstrated in experiments in which distal delivery was increased by contralateral nephrectomy or by administration of carbonic anhydrase inhibitors which decrease proximal sodium reabsorption. In both studies, fractional free water clearance increased markedly reaching levels significantly greater than in euthyroid controls. These results demonstrate that the impaired ability of the hypothyroid rat to excrete a water load is not due to incomplete suppression of ADH or decreased reabsorptive capacity of the diluting segment

  9. Subchondral bone loss following orthodontically induced cartilage degradation in the mandibular condyles of rats.

    PubMed

    Jiao, Kai; Niu, Li-Na; Wang, Mei-Qing; Dai, Juan; Yu, Shi-Bin; Liu, Xiao-Dong; Wang, Jun

    2011-02-01

    Osteoarthritis (OA) is a degenerative joint disease generally characterized by progressive cartilage degradation and subchondral bone changes. Subchondral bone changes have been proposed to initiate or accompany with cartilage degradation in OA. The purpose of this study was to characterize cartilage damage, subchondral bone remodeling, and the possible mechanism involved in these morphological changes in our reported rat model with OA-like lesions in the mandibular condyle. In experimental groups, the dental occlusion was orthodontically disturbed. By histological analysis, transmission electron microscopy (TEM), micro-CT scanning and serum tests, changes in condylar cartilage and subchondral bone were analyzed at 8 and 12 weeks after treatment. The mRNA and protein levels of bone pro-resorptive and pro-formative factors by chondrocytes were investigated. Increased degraded cartilage areas and obvious cartilage calcification were observed in 8- and 12-week treated (EXP) groups compared to the age-matched controls. Subchondral bone loss, characterized as decreased bone mineral density (BMD), bone volume fraction (BV/TV) and trabecular thickness (Tb.Th), but increased trabecular separation (Tb.Sp), was observed in the 12-week but not the 8-week EXP group, respectively, versus their age-matched controls. The subchondral bone loss in the 12-week EXP group was accompanied with decreased new bone formation rate, but increased serum carboxy terminal telopeptides (CTXs), and increased osteoclast numbers and proportion of surface area in the subchondral bone regions. Increased mRNA and protein levels of M-CSF, VEGF, RUNX and RANKL/OPG ratio, but decreased OPG, were found in condylar cartilage in the 12-week EXP group versus its age-matched controls, and those of RANKL/OPG ratios were significantly higher in the 12-week EXP group than the 8-week EXP. In addition, increased mRNA levels of VEGF, RUNX and RANKL/OPG ratio, but decreased OPG, were also found in condylar

  10. 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.

  11. Changes in rat soleus muscle phenotype consecutive to a growth in hypergravity followed by normogravity.

    PubMed

    Picquet, F; Bouet, V; Cochon, L; Lacour, M; Falempin, M

    2005-07-01

    It has been demonstrated that a long-term stay in hypergravity (HG: 2G) modified the phenotype and the contractile properties of rat soleus muscle. The ability of this muscle to contract was drastically reduced, which is a sign of anticipated aging. Consequently, our aim was to determine whether rats conceived, born, and reared in hypergravity showed adaptative capacities in normogravity (NG: 1G). This study was performed on rats divided into two series: the first was reared in HG until 100 days and was submitted to normogravity until 115 to 220 postnatal days (HG-NG rats); the second was made up of age paired groups reared in normogravity (NG rats). The contractile, morphological, and phenotypical properties of soleus muscle were studied. Our results showed that the NG rats were characterized by coexpressions of slow and fast myosin, respectively, 76.5 and 23.5% at 115 days. During their postnatal maturation, the fast isoform was gradually replaced by slow myosin. At 220 days, the relative proportions were respectively 91.05% and 8.95%. From 115 to 220 days, the HG-NG rats expressed 100% of slow myosin isoform and they presented a slower contractile behavior compared with their age-matched groups; at 115 days, the whole muscle contraction time was increased by 35%, and by 15%, at 220 days. Our study underlined the importance of gravity in the muscular development and suggested the existence of critical periods in muscle phenotype installation.

  12. Cardiac pathology in the hypertensive diabetic rat. Biventricular damage with right ventricular predominance.

    PubMed Central

    Fein, F. S.; Cho, S.; Zola, B. E.; Miller, B.; Factor, S. M.

    1989-01-01

    The hypertensive-diabetic rat is a new small animal model of cardiomyopathy characterized by ventricular damage. To determine the extent of pathology in this model, quantitation of light microscopic changes in hearts from 15 hypertensive-diabetic rats and 15 age-matched controls was performed. The fraction of myocardium involved by interstitial fibrosis, myocyte necrosis, replacement fibrosis, vascular sclerosis and perivascular fibrosis was computed separately for right and left ventricles. Spontaneously dying as well as deliberately killed hypertensive-diabetic rats were studied. Spontaneously dying animals had higher systolic blood pressures compared with rats killed deliberately. Body weights were lower and lung weights higher in the former group. Left and right ventricular necrosis and fibrosis were increased in spontaneously dying compared with deliberately killed rats. The degree of right ventricular necrosis and fibrosis paralleled that in the left ventricle, but was, unexpectedly, several times greater in magnitude. Thus, quantitative histology in the hypertensive-diabetic rat reveals more cardiac necrosis and fibrosis, in either ventricle, from spontaneously dying animals compared with deliberately killed rats. This damage, coupled with major functional alterations in the viable myocardium, may lead to congestive heart failure or arrhythmia. Images Figure 1 Figure 2 PMID:2719080

  13. Tocotrienol rich fraction reverses age-related deficits in spatial learning and memory in aged rats.

    PubMed

    Taridi, Nursiati Mohamad; Abd Rani, Nazirah; Abd Latiff, Azian; Ngah, Wan Zurinah Wan; Mazlan, Musalmah

    2014-09-01

    Little is known about the effect of vitamin E on brain function. Therefore, in this study we evaluated the effect of tocotrienol rich fraction (TRF) on behavioral impairment and oxidative stress in aged rats. Thirty-six male Wistar rats (young: 3-months-old; aged: 21-months-old) were treated with either the control (olive oil) or TRF (200 mg/kg) for 3 months. Behavioral studies were performed using the open field test and Morris water maze (MWM) task. Blood was taken for assessment of DNA damage, plasma malondialdehyde (MDA) and vitamin E, and erythrocyte antioxidant enzyme activity. Brains were also collected to measure vitamin E levels. Results showed that aged rats exhibited reduced exploratory activity, enhanced anxiety and decreased spatial learning and memory compared with young rats. DNA damage and plasma MDA were increased, and vitamin E levels in plasma and brain were reduced in aged rats. Aged rats supplemented with TRF showed a markedly reduced level of anxiety, improved spatial learning and memory, reduced amount and severity of DNA damage, a reduced level of MDA, and increased levels of antioxidant enzyme activity and plasma/brain vitamin E compared with age-matched controls. In conclusion, TRF supplementation reverses spatial learning and memory decline and decreases oxidative stress in aged rats.

  14. Mothers do it differently: reproductive experience alters fear extinction in female rats and women

    PubMed Central

    Milligan-Saville, J S; Graham, B M

    2016-01-01

    Fear extinction is the laboratory basis of exposure therapy for anxiety disorders. Recent findings have revealed that estradiol is necessary to the consolidation of extinction memories in females. These findings are based on studies conducted using virgin rats and young women whose reproductive history is unknown. We hypothesized that motherhood, which results in extensive endocrinological, neurobiological and behavioral changes, may lead to alterations in fear extinction in females. We used a cross-species translational approach to investigate the impact of reproductive experience on fear extinction and fear relapse in female rats (n=116) and women (n=64). Although freezing during extinction recall was associated with estrous cycle phase during extinction training in virgin rats, this association was mitigated in age-matched reproductively experienced rats, even when fear extinction occurred 3 months after pups had been weaned, and even though reproductively experienced rats exhibited attenuated serum estradiol levels. In addition, although serum estradiol levels predicted extinction recall in human women with no prior reproductive experience, no such association was found in women with children. Finally, although virgin rats displayed both renewal and reinstatement after fear extinction, these common relapse phenomena were absent in rats with reproductive experience. Together, these findings suggest that reproductive experience alters the endocrine and behavioral features of fear extinction in females long after the hormonal surges of pregnancy and lactation have diminished. These results highlight the need to incorporate both hormonal and reproductive status as important factors in current models of fear extinction in females. PMID:27779622

  15. Decreased Neuronal Bursting and Phase Synchrony in the Hippocampus of Streptozotocin Diabetic Rats

    PubMed Central

    Xie, Kangning; Li, Guoliang

    2014-01-01

    Diabetic encephalopathy is one of the complications of diabetes. Cognitive dysfunction is the main consequence. Previous findings from neuroanatomical and in vitro electrophysiological studies showed that the structure and function of the hippocampus is impaired in diabetes, which may underlie the cognitive dysfunction induced by diabetes. However the study of electrophysiological abnormality of hippocampal neurons in intact networks is sparse. In the current study, we recorded the spontaneous firing of neurons in hippocampal CA1 area in anesthetized streptozotozin (STZ)-diabetic and age-matched control rats. Profound reduction in burst activity was found in diabetic rats. Compared to control rats, the intra-burst inter-spike intervals were prolonged significantly in diabetic rats, while the burst ratio and the mean number of spikes within a burst decreased significantly. Treatment with APP 17-mer peptide retarded the effects of diabetes on these parameters. In addition, the average PLV of diabetic rats was lower than that of control rats. These findings provide in vivo electrophysiological evidence for the impairment of hippocampal function in STZ-diabetic rats, and may have some implications in the mechanisms associated with cognitive deficits in diabetes. PMID:25093193

  16. Tongue Fat Infiltration in Obese Versus Lean Zucker Rats

    PubMed Central

    Brennick, Michael J.; Delikatny, James; Pack, Allan I.; Pickup, Stephen; Shinde, Sarika; Zhu, Jing-Xu; Roscoe, Ivana; Kim, David Y.; Buxbaum, Laurence U.; Cater, Jacqueline R.; Schwab, Richard J.

    2014-01-01

    Study Objectives: Obesity is the most important risk factor for obstructive sleep apnea (OSA), and the effects of obesity may be mediated by tongue fat. Our objective was to examine the effects of obesity on upper airway structures in obese (OBZ) and non-obese (NBZ) Zucker rats. Design: Animal study. Setting: Academic Medical Center. Participants: OBZ (638.2 ± 39 g; 14.9 ± 1.1 w) and age-matched NBZ Zucker (442.6 ± 37 g, 15.1 ± 1.5 w) rats. Interventions: Tongue fat and volume and were assessed using: in vivo magnetic resonance spectroscopy (MRS), magnetic resonance imaging including Dixon imaging for tongue fat volume, ex vivo biochemistry (fat quantification; triglyceride (mg)/tissue (g), and histology (Oil Red O stain). Measurements and Results: MRS: overall OBZ tongue fat/water ratio was 2.9 times greater than NBZ (P < 0.002) with the anterior OBZ tongue up to 3.3 times greater than NBZ (P < 0.002). Biochemistry: Triglyceride (TG) in the tongue was 4.4 times greater in OBZ versus NBZ (P < 0.0006). TG was greater in OBZ tongue (3.57 ± 1.7 mg/g) than OBZ masseter muscle (0.28 ± 0.1; P < 0.0001) but tongue and masseter TG were not different in NBZ rats (0.82 ± 0.3 versus 0.28 ± 0.1 mg/g, P = 0.67). Dixon fat volume was significantly increased in OBZ (56 ± 15 mm3) versus NBZ (34 ± 5 mm3, P < 0.004). Histology demonstrated a greater degree of intracellular muscle fat and extramuscular fat infiltration in OBZ versus NBZ rats. Conclusions: Genetically obese rats had a large degree of fat infiltration in the tongue compared to both skeletal muscle and tongue tissues of the non-obese age-matched littermates. The significant fat increase and sequestration in the obese tongue may play a role in altered tongue neuromuscular function, tongue stiffness or metabolic function. Citation: Brennick MJ, Delikatny J, Pack AI, Pickup S, Shinde S, Zhu JX, Roscoe I, Kim DY, Buxbaum LU, Cater JR, Schwab RJ. Tongue fat infiltration in obese versus lean Zucker rats. SLEEP 2014

  17. Non-alcoholic steatohepatitis and preneoplastic lesions develop in the liver of obese and hypertensive rats: suppressing effects of EGCG on the development of liver lesions.

    PubMed

    Kochi, Takahiro; Shimizu, Masahito; Terakura, Daishi; Baba, Atsushi; Ohno, Tomohiko; Kubota, Masaya; Shirakami, Yohei; Tsurumi, Hisashi; Tanaka, Takuji; Moriwaki, Hisataka

    2014-01-01

    Non-alcoholic steatohepatitis (NASH), which involves hepatic inflammation and fibrosis, is associated with liver carcinogenesis. The activation of the renin-angiotensin system (RAS), which plays a key role in blood pressure regulation, promotes hepatic fibrogenesis. In this study, we investigated the effects of (-)-epigallocatechin-3-gallate (EGCG), a major component of green tea catechins, on the development of glutathione S-transferase placental form (GST-P)-positive (GST-P(+)) foci, a hepatic preneoplastic lesion, in SHRSP.Z-Lepr(fa)/IzmDmcr (SHRSP-ZF) obese and hypertensive rats. Male 7-week-old SHRSP-ZF rats and control non-obese and normotensive WKY rats were fed a high fat diet and received intraperitoneal injections of carbon tetrachloride twice a week for 8weeks. The rats were also provided tap water containing 0.1% EGCG during the experiment. SHRSP-ZF rats presented with obesity, insulin resistance, dyslipidemia, an imbalance of adipokines in the serum, and hepatic steatosis. The development of GST-P(+) foci and liver fibrosis was markedly accelerated in SHRSP-ZF rats compared to that in control rats. Additionally, in SHRSP-ZF rats, RAS was activated and inflammation and oxidative stress were induced. Administration of EGCG, however, inhibited the development of hepatic premalignant lesions by improving liver fibrosis, inhibiting RAS activation, and attenuating inflammation and oxidative stress in SHRSP-ZF rats. In conclusion, obese and hypertensive SHRSP-ZF rats treated with a high fat diet and carbon tetrachloride displayed the histopathological and pathophysiological characteristics of NASH and developed GST-P(+) foci hepatic premalignant lesions, suggesting the model might be useful for the evaluation of NASH-related liver tumorigenesis. EGCG might also be able to prevent NASH-related liver fibrosis and tumorigenesis.

  18. Shortened Conditioned Eyeblink Response Latency in Male but not Female Wistar-Kyoto Hyperactive Rats

    PubMed Central

    Thanellou, Alexandra; Schachinger, Kira M.; Green, John T.

    2014-01-01

    Reductions in the volume of the cerebellum and impairments in cerebellar-dependent eyeblink conditioning have been observed in attention-deficit/hyperactivity disorder (ADHD). Recently, it was reported that subjects with ADHD as well as male spontaneously hypertensive rats (SHR), a strain that is frequently employed as an animal model in the study of ADHD, exhibit a parallel pattern of timing deficits in eyeblink conditioning. One criticism that has been posed regarding the validity of the SHR strain as an animal model for the study of ADHD is that SHRs are not only hyperactive but also hypertensive. It is conceivable that many of the behavioral characteristics seen in SHRs that seem to parallel the behavioral symptoms of ADHD are not solely due to hyperactivity but instead are the net outcome of the interaction between hyperactivity and hypertension. We used Wistar-Kyoto Hyperactive (WKHA) and Wistar-Kyoto Hypertensive (WKHT) rats (males and females), strains generated from recombinant inbreeding of SHRs and their progenitor strain, Wistar-Kyoto (WKY) rats, to compare eyeblink conditioning in strains that are exclusively hyperactive or hypertensive. We used a long-delay eyeblink conditioning task in which a tone conditioned stimulus was paired with a periorbital stimulation unconditioned stimulus (750-ms delay paradigm). Our results showed that WKHA and WKHT rats exhibited similar rates of conditioned response (CR) acquisition. However, WKHA males displayed shortened CR latencies (early onset and peak latency) in comparison to WKHT males. In contrast, female WKHAs and WKHTs did not differ. In subsequent extinction training, WKHA rats extinguished at similar rates in comparison to WKHT rats. The current results support the hypothesis of a relationship between cerebellar abnormalities and ADHD in an animal model of ADHD-like symptoms that does not also exhibit hypertension, and suggest that cerebellar-related timing deficits are specific to males. PMID:19485572

  19. 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

  20. Effect of methylphenidate treatment during adolescence on norepinephrine transporter function in orbitofrontal cortex in a rat model of attention deficit hyperactivity disorder.

    PubMed

    Somkuwar, Sucharita S; Kantak, Kathleen M; Dwoskin, Linda P

    2015-08-30

    Attention deficit hyperactivity disorder (ADHD) is associated with hypofunctional medial prefrontal cortex (mPFC) and orbitofrontal cortex (OFC). Methylphenidate (MPH) remediates ADHD, in part, by inhibiting the norepinephrine transporter (NET). MPH also reduces ADHD-like symptoms in spontaneously hypertensive rats (SHRs), a model of ADHD. However, effects of chronic MPH treatment on NET function in mPFC and OFC in SHR have not been reported. In the current study, long-term effects of repeated treatment with a therapeutically relevant oral dose of MPH during adolescence on NET function in subregions of mPFC (cingulate gyrus, prelimbic cortex and infralimbic cortex) and in the OFC of adult SHR, Wistar-Kyoto (WKY, inbred control) and Wistar (WIS, outbred control) rats were determined using in vivo voltammetry. Following local ejection of norepinephrine (NE), uptake rate was determined as peak amplitude (Amax)× first-order rate constant (k-1). In mPFC subregions, no strain or treatment effects were found in NE uptake rate. In OFC, NE uptake rate in vehicle-treated adult SHR was greater than in adult WKY and WIS administered vehicle. MPH treatment during adolescence normalized NE uptake rate in OFC in SHR. Thus, the current study implicates increased NET function in OFC as an underlying mechanism for reduced noradrenergic transmission in OFC, and consequently, the behavioral deficits associated with ADHD. MPH treatment during adolescence normalized NET function in OFC in adulthood, suggesting that the therapeutic action of MPH persists long after treatment cessation and may contribute to lasting reductions in deficits associated with ADHD.

  1. Soluble epoxide hydrolase inhibition and peroxisome proliferator activated receptor γ agonist improve vascular function and decrease renal injury in hypertensive obese rats.

    PubMed

    Imig, John D; Walsh, Katie A; Hye Khan, Md Abdul; Nagasawa, Tasuku; Cherian-Shaw, Mary; Shaw, Sean M; Hammock, Bruce D

    2012-12-01

    Cardiometabolic syndrome occurs with obesity and consists of pathophysiological factors that increase the risk for cardiovascular events. Soluble epoxide hydrolase inhibition (sEHi) is a novel therapeutic approach that exerts renal and cardiovascular protection. Although sEHi as a therapeutic approach is promising, it could be more effective for the treatment of cardiometabolic syndrome when combined with peroxisome proliferator activated receptor γ (PPARγ) agonists. We hypothesized that the PPARγ agonist, rosiglitazone in combination with a sEHi (tAUCB) will provide synergistic actions to decrease blood pressure, improve vascular function, decrease inflammation, and prevent renal damage in spontaneously hypertensive obese rats (SHROB). SHROB were treated with rosiglitazone, tAUCB or the combination of tAUCB and rosiglitazone for four-weeks and compared with spontaneously hypertensive (SHR) and Wistar-Kyoto (WKY) rats. Blood pressure increased in SHROB (164 ± 7 mmHg) and decreased 10 mmHg when treated with rosiglitazone, tAUCB, or tAUCB and rosiglitazone. Mesenteric artery dilation to the K(ATP) channel opener pinacidil was attenuated in SHROB (E(Max) = 77 ± 7%), compared with WKY (E(Max) = 115 ± 19) and SHR (E(Max) = 93 ± 12%). Vasodilation to pinacidil was improved by rosiglitazone (E(Max) = 92 ± 14%) but not tAUCB. Renal macrophage infiltration increased in SHROB and significantly decreased with rosiglitazone or tAUCB and rosiglitazone treatment. Albuminuria was increased in SHROB (90 ± 20 mg/d) and was significantly decreased by the combination of tAUCB and rosiglitazone (37 ± 9 mg/d). Glomerular injury in SHROB was also significantly decreased by tAUCB and rosiglitazone. These results indicate that even though sEHi or PPARγ agonist have benefits when used individually, the combination is more beneficial for the multidisease features in cardiometabolic syndrome.

  2. Soluble epoxide hydrolase inhibition and peroxisome proliferator activated receptor γ agonist improve vascular function and decrease renal injury in hypertensive obese rats

    PubMed Central

    Imig, John D; Walsh, Katie A; Khan, Md Abdul Hye; Nagasawa, Tasuku; Cherian-Shaw, Mary; Shaw, Sean M; Hammock, Bruce D

    2013-01-01

    Cardiometabolic syndrome occurs with obesity and consists of pathophysiological factors that increase the risk for cardiovascular events. Soluble epoxide hydrolase inhibition (sEHi) is a novel therapeutic approach that exerts renal and cardiovascular protection. Although sEHi as a therapeutic approach is promising, it could be more effective for the treatment of cardiometabolic syndrome when combined with peroxisome proliferator activated receptor γ (PPARγ) agonists. We hypothesized that the PPARγ agonist, rosiglitazone in combination with a sEHi (tAUCB) will provide synergistic actions to decrease blood pressure, improve vascular function, decrease inflammation, and prevent renal damage in spontaneously hypertensive obese rats (SHROB). SHROB were treated with rosiglitazone, tAUCB or the combination of tAUCB and rosiglitazone for four-weeks and compared with spontaneously hypertensive (SHR) and Wistar–Kyoto (WKY) rats. Blood pressure increased in SHROB (164 ±7 mmHg) and decreased 10 mmHg when treated with rosiglitazone, tAUCB, or tAUCB and rosiglitazone. Mesenteric artery dilation to the KATP channel opener pinacidil was attenuated in SHROB (EMax = 77 ±7%), compared with WKY (EMax = 115 ±19) and SHR (EMax = 93 ±12%). Vasodilation to pinacidil was improved by rosiglitazone (EMax = 92 ±14%) but not tAUCB. Renal macrophage infiltration increased in SHROB and significantly decreased with rosiglitazone or tAUCB and rosiglitazone treatment. Albuminuria was increased in SHROB (90 ±20 mg/d) and was significantly decreased by the combination of tAUCB and rosiglitazone (37 ±9 mg/d). Glomerular injury in SHROB was also significantly decreased by tAUCB and rosiglitazone. These results indicate that even though sEHi or PPARγ agonist have benefits when used individually, the combination is more beneficial for the multidisease features in cardiometabolic syndrome. PMID:23354399

  3. Effect of methylphenidate treatment during adolescence on norepinephrine transporter function in orbitofrontal cortex in a rat model of Attention Deficit Hyperactivity Disorder

    PubMed Central

    Somkuwar, Sucharita S.; Kantak, Kathleen M.; Dwoskin, Linda P.

    2015-01-01

    Attention Deficit Hyperactivity Disorder (ADHD) is associated with hypofunctional medial prefrontal cortex (mPFC) and orbitofrontal cortex (OFC). Methylphenidate (MPH) remediates ADHD, in part, by inhibiting the norepinephrine transporter (NET). MPH also reduces ADHD-like symptoms in Spontaneously Hypertensive Rats (SHRs), a model of ADHD. However, effects of chronic MPH treatment on NET function in mPFC and OFC in SHR have not been reported. In the current study, long-term effects of repeated treatment with a therapeutically relevant oral dose of MPH during adolescence on NET function in subregions of mPFC (cingulate gyrus, prelimbic cortex and infralimbic cortex) and in the OFC of adult SHR, Wistar-Kyoto (WKY, inbred control) and Wistar (WIS, outbred control) rats were determined using in vivo voltammetry. Following local ejection of norepinephrine (NE), uptake rate was determined as peak amplitude (Amax) x first-order rate constant (k-1). In mPFC subregions, no strain or treatment effects were found in NE uptake rate. In OFC, NE uptake rate in vehicle-treated adult SHR was greater than in adult WKY and WIS administered vehicle. MPH treatment during adolescence normalized NE uptake rate in OFC in SHR. Thus, the current study implicates increased NET function in OFC as an underlying mechanism for reduced noradrenergic transmission in OFC, and consequently, the behavioral deficits associated with ADHD. MPH treatment during adolescence normalized NET function in OFC in adulthood, suggesting that the therapeutic action of MPH persists long after treatment cessation and may contribute to lasting reductions in deficits associated with ADHD. PMID:25680322

  4. 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.

  5. Heart failure alters matrix metalloproteinase gene expression and activity in rat skeletal muscle.

    PubMed

    Carvalho, Robson Francisco; Dariolli, Rafael; Justulin Junior, Luis Antonio; Sugizaki, Mário Mateus; Politi Okoshi, Marina; Cicogna, Antonio Carlos; Felisbino, Sérgio Luis; Dal Pai-Silva, Maeli

    2006-12-01

    Heart failure is associated with a skeletal muscle myopathy with cellular and extracellular alterations. The hypothesis of this investigation is that extracellular changes may be associated with enhanced mRNA expression and activity of matrix metalloproteinases (MMP). We examined MMP mRNA expression and MMP activity in Soleus (SOL), extensor digitorum longus (EDL), and diaphragm (DIA) muscles of young Wistar rat with monocrotaline-induced heart failure. Rats injected with saline served as age-matched controls. MMP2 and MMP9 mRNA contents were determined by RT-PCR and MMP activity by electrophoresis in gelatin-containing polyacrylamide gels in the presence of SDS under non-reducing conditions. Heart failure increased MMP9 mRNA expression and activity in SOL, EDL and DIA and MMP2 mRNA expression in DIA. These results suggest that MMP changes may contribute to the skeletal muscle myopathy during heart failure.

  6. 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

  7. 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

  8. 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.

  9. Chronic administration of sildenafil improves erectile function in a rat model of chronic renal failure

    PubMed Central

    Gurbuz, Nilgun; Kol, Arif; Ipekci, Tumay; Ates, Erhan; Baykal, Asli; Usta, Mustafa F

    2015-01-01

    The relationship between erectile dysfunction (ED) and chronic renal failure (CRF) has been reported in several studies. This study aimed to investigate whether the chronic use of sildenafil could enhance the erectile capacity in CRF-induced rats. In addition, we assessed the effect of that treatment on certain molecules, which have been suggested to play crucial roles in erectile physiology and CRF-related ED as well. Three groups of animals were utilized: (1) age-matched control rats, (2) CRF-induced rats, (3) CRF-induced rats treated with chronic administration of sildenafil (5 mg kg−1 p.o. for 6 weeks [treatment started after 6 weeks of CRF induction]). At 3 months, all animals underwent cavernosal nerve stimulation (CNS) to assess erectile function. Penile tissue advanced glycation end products (AGE's)/5-hydroxymethyl-2-furaldehyde, malondialdehyde (MDA), cGMP (ELISA), inducible nitric oxide synthase (iNOS) and neuronal NOS (nNOS) (Western blot) analyses were performed in all rat groups. CRF-induced rats had a significant decrease in erectile function when compared to control rats (P < 0.05). The increase in both intracavernosal pressure (ICP) and area under the curve of CRF-induced rats treated with sildenafil (Group 3) was greater than CRF-induced rats (Group 2). Additionally, sildenafil treatment decreased AGE, MDA and iNOS levels, while it preserved nNOS and cGMP contents in CRF-induced penile tissue. Decreased AGE, MDA, iNOS and increased nNOS, cGMP levels at the sildenafil-treated group increased both ICP and Total ICP to CNS, which led to improve erectile function in CRF-induced rats. The results of the present study revealed the therapeutic effect of chronic sildenafil administration on erectile function in CRF-induced rats. PMID:25652632

  10. A Comparative Study of Vasorelaxant Effects of ATP, ADP, and Adenosine on the Superior Mesenteric Artery of SHR.

    PubMed

    Watanabe, Shun; Matsumoto, Takayuki; Ando, Makoto; Kobayashi, Shota; Iguchi, Maika; Taguchi, Kumiko; Kobayashi, Tsuneo

    2016-01-01

    We investigated superior mesenteric arteries from spontaneously hypertensive rats (SHR) to determine the relaxation responses induced by ATP, ADP, and adenosine and the relationship between the relaxant effects of these compounds and nitric oxide (NO) or cyclooxygenase (COX)-derived prostanoids. In rat superior mesenteric artery, relaxation induced by ATP and ADP but not by adenosine was completely eliminated by endothelial denudation. In the superior mesenteric arteries isolated from SHR [vs. age-matched control Wistar Kyoto rats (WKY)], a) ATP- and ADP-induced relaxations were weaker, whereas adenosine-induced relaxation was similar in both groups, b) ATP- and ADP-induced relaxations were substantially and partly reduced by N(G)-nitro-L-arginine [a NO synthase (NOS) inhibitor], respectively, c) indomethacin, an inhibitor of COX, increased ATP- and ADP-induced relaxations, d) ADP-induced relaxation was weaker under combined inhibition by NOS and COX, and e) adenosine-induced relaxation was not altered by treatment with these inhibitors. These data indicate that levels of responsiveness to these nucleotides/adenosine vary in the superior mesenteric arteries from SHR and WKY and are differentially modulated by NO and COX-derived prostanoids.

  11. Breeder and Batch-Dependent Variability in the Acquisition and Performance of a Motor Skill in Adult Long-Evans Rats

    PubMed Central

    O’Bryan, Amber J.; Allred, Rachel P.; Maldonado, Monica A.; Cormack, Lawrence K.; Jones, Theresa A.

    2011-01-01

    Reaching tasks are popular tools for investigating the neural mechanisms of motor skill learning and recovery from brain damage in rodents, but there is considerable unexplained variability across studies using these tasks. We investigated whether breeder, batch effects, experimenter, time of year, weight and other factors contribute to differences in the acquisition and performance of a skilled reaching task, the single pellet retrieval task, in adult male Long-Evans hooded rats. First, we retrospectively analyzed task acquisition and performance in rats from different breeding colonies that were used in several studies spanning a three year period in our laboratory. Second, we compared reaching variables in age-matched rats from different breeders that were trained together as a batch by the same experimenters. All rats had received daily training on the reaching task until they reached a criterion of successful reaches per attempt. We found significant breeder-dependent differences in learning rate and final performance level. This was found even when age-matched rats from different breeders were trained together by the same experimenters. There was also significant batch-to-batch variability within rats from the same breeder trained by the same experimenter. Other factors, including weight, paw preference and the experimenter, were not as strong or consistent in their contributions to differences across studies. The breeder and batch effects found within the same rat strain may reflect genetic and environmental influences on the neural substrates of motor skill learning. This is an important consideration when comparing baseline performance across studies and for controlling variability within studies. PMID:21664381

  12. Susceptibility of natural killer cell activity of old rats to stress.

    PubMed Central

    Ghoneum, M; Gill, G; Assanah, P; Stevens, W

    1987-01-01

    We determined an in vivo response of NK cells in young and old rats towards the suppressive effect of stress. Stress was developed by isolating rats in separate cages, but control littermates were kept together. Animals were subjected to stress for 7 days, and alterations of NK cell activities were examined in the spleen, peripheral blood (PB) and bone marrow (BM). The results showed that old rats subjected to stress had a remarkable decrease in splenic and PB-NK activity compared to old control rats, concomitant with a highly increased level of NK cell activity in BM. Suppression of the lytic activity in the spleen of stressed old rats was correlated with a decrease in the percentage of conjugate formation between splenic NK cells and target tumour cells. In contrast, stressed young rats demonstrated relatively unchanged activity of NK cells examined in different tissues compared to age-matched controls. We concluded that old animals are more sensitive to the suppressive effect of stress compared to young ones, and the mechanism of this suppression is probably due to the migration of large granular lymphocytes (LGL) from spleen and PB to other sites such as BM. PMID:3570358

  13. Strain differences in urinary factors that promote calcium oxalate crystal formation in the kidneys of ethylene glycol-treated rats.

    PubMed

    Li, Yan; McMartin, Kenneth E

    2009-05-01

    Ethylene glycol (EG)-induced hyperoxaluria is the most commonly employed experimental regimen as an animal model of calcium oxalate (CaOx) stone formation. The variant sensitivity to CaOx among different rat strains has not been fully explored, although the Wistar rat is known to accumulate more CaOx in kidney tissue after low-dose EG exposure than in the Fischer 344 (F344) rats. Supersaturation of CaOx in tubular fluid contributes to the amount of CaOx crystal formation in the kidney. We hypothesized that the urinary supersaturation of CaOx in Wistar rats is higher than that of F344 rats, thereby allowing for greater CaOx crystal deposition in the Wistar rat. Age-matched male Wistar and F344 rats were treated with 0.75% EG or drinking water for 8 wk. Twenty-four-hour urine was collected at 0, 2, 4, 6, and 8 wk for analysis of key electrolytes to calculate the CaOx supersaturation. Plasma oxalate level was also measured. Our data confirmed the different sensitivity to renal toxicity from EG between the two rat strains (Wistar > F344). After EG treatment, the plasma oxalate level and urine oxalate excretion were markedly greater in the Wistar rats than in the F344 rats, while urine calcium was slightly decreased in Wistars. Thus, the CaOx supersaturation in urine of Wistar rats was higher, which led to a greater crystal deposition in kidney in Wistar rats. These studies suggest that during EG treatment, changes in urine electrolytes and in CaOx supersaturation occur to a greater extent in the Wistar rat, in agreement with its greater sensitivity to EG toxicity.

  14. 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.

  15. Long-term intake of sesamin improves left ventricular remodelling in spontaneously hypertensive rats.

    PubMed

    Li, Wen-xing; Kong, Xiang; Zhang, Jun-xiu; Yang, Jie-ren

    2013-02-26

    This study was designed to evaluate the in vivo cardioprotective effects of food-derived sesamin in spontaneously hypertensive rats (SHR). The study was performed with 17-week-old male normotensive Wistar-Kyoto rats (WKY) and SHR which are untreated or treated with orally administered sesamin for 16 weeks before they were sacrificed. Long-term treatment with sesamin obviously improved left ventricular (LV) hypertrophy and fibrosis in SHR, as indicated by the decrease of LV weight/body weight, myocardial cell size, cardiac fibrosis and collagen type I expression as well as the amelioration of the LV ultrastructure. These effects were associated with reduced systolic blood pressure, enhanced cardiac total antioxidant capability and decreased malondialdehyde content, nitrotyrosine level and transforming growth factor β1 (TGF-β1) expression. All these results suggest that chronic treatment with sesamin improves LV remodeling in SHR through alleviation of oxidative and nitrative stress, reduction of blood pressure and downregulation of TGF-β1 expression.

  16. Protective effect of nicardipine treatment on cerebrovascular microanatomical changes in spontaneously hypertensive rats.

    PubMed

    Amenta, F; Ferrante, F; Ricci, A; Sabbatini, M

    1995-12-01

    1. The effect of long-term treatment with the dihydropyridine Ca2+ antagonist, nicardipine, on the morphology of different sized pial arteries was assessed in spontaneously hypertensive rats (SHR) using histological techniques associated with image analysis. 2. In control 20 week old SHR blood pressure values, the thickness of the tunica media, the media-to-lumen ratio and connective tissue content were significantly increased in comparison with reference normotensive Wistar-Kyoto (WKY) rats. 3. Treatment for 8 weeks with a daily dose of 3 mg/kg of nicardipine decreased blood pressure values in SHR and significantly reduced the area occupied by the tunica media and the media-to-lumen ratio. This effect was observed primarily in small sized pial arteries and to a lesser extent in medium sized pial arteries. Nicardipine administration was without effect on connective tissue content in the wall of cerebral arteries. 4. These results indicate that treatment with nicardipine reduces blood pressure elevation in SHR and exerts a protective effect on arteries controlling cerebrovascular resistance. The activity of the compound primarily on small sized pial arteries may protect the brain from generalized vasodilation which could cause cerebral hypoperfusion.

  17. Spontaneously hypertensive rats: a potential model to identify drugs for treatment of learning disorders.

    PubMed

    Meneses, A; Hong, E

    1998-04-01

    Spontaneously hypertensive rats (SHR) of 3 to 12 months of age learned and retrieved less information than normotensive Wistar-Kyoto rats (WKY), although no difference was found with animals from 18 and 24 months of age. The combined influence of hypertension and aging had an additive detrimental effect on cognitive functions. Notwithstanding these deficiencies in learning and memory, SHR have seldom been used as a model in the screening of drugs with therapeutic potential for treatment of disorders of cognitive processes. Moreover, the calcium channel blocker nimodipine has beneficial effects on learning in both aged and hypertensive animals and humans. However, no attempt has been made to investigate whether nimodipine can reverse the additive deleterious effects of aging and hypertension in the same subject. We recently reported that deteriorated animals (middle-aged and/or hypertensive) chronically treated with nimodipine (via osmotic minipumps) exhibit higher learning scores. This information indicates that nimodipine can reverse the impairing effects of either aging or hypertension on learning; the presence of the two conditions, however, produces a severe impairment that can be partially reversed by this drug. Therefore, we propose that mature and middle-aged SHR represent a model for the screening of potentially useful drugs in the treatment of learning disorders, probably associated with hypertension and/or aging. Nevertheless, it must be remembered that the SHR is a genetic model and the appearance of neural disturbances could be a parallel genetic phenomenon and not necessarily or exclusively related to hypertension per se.

  18. Elevated levels of the serum endogenous inhibitor of nitric oxide synthase and metabolic control in rats with streptozotocin-induced diabetes.

    PubMed

    Xiong, Yan; Fu, Yun-feng; Fu, Si-hai; Zhou, Hong-hao

    2003-08-01

    This study was designed to determine the relationship between elevated levels of the endogenous inhibitor of nitric oxide synthase, asymmetric dimethylarginine (ADMA), and metabolic control in rats with streptozotocin-induced diabetes. Serum levels of ADMA were measured by high-performance liquid chromatography at 8 weeks after diabetes was induced. Endothelium-dependent relaxation to acetylcholine was tested in aortic rings from nondiabetic age-matched control, untreated diabetic, and insulin-treated diabetic rats to evaluate endothelial function. Serum concentrations of glucose, glycosylated serum protein, and malondialdehyde were examined to estimate metabolic control. Serum levels of ADMA increased dramatically in untreated diabetic rats compared with control rats. This elevation in ADMA levels was accompanied by impairment of the endothelium-dependent relaxation response to acetylcholine in aortic rings. Long-term insulin treatment not only prevented the elevation of serum ADMA levels, but also improved the impairment of endothelium-dependent relaxation in diabetic rats. Serum levels of glucose, glycosylated serum protein, and malondialdehyde were significantly increased in parallel with the elevation of ADMA in untreated diabetic rats compared with control rats. These parameters were normalized after diabetic rats received insulin treatment for 8 weeks. These results provide the first evidence that an elevation in the concentration of ADMA in rats with streptozotocin-induced diabetes is closely related to metabolic control of the disease.

  19. Further dissection of a genomic locus associated with behavioral activity in the Wistar-Kyoto hyperactive rat, an animal model of hyperkinesis.

    PubMed

    Moisan, M-P; Llamas, B; Cook, M N; Mormède, P

    2003-03-01

    Molecular genetic studies of attention-deficit hyperactivity disorder (ADHD) are a major focus of current research since this syndrome has been shown to be highly heritable.(1) Our approach has been to search for quantitative trait loci (QTL) in a genetic animal model of hyperkinesis, the Wistar-Kyoto hyperactive (WKHA) rat, by a whole-genome scan analysis. In a previous article, we reported the detection of a major QTL associated with behavioral activity in an F2 cross between WKHA and Wistar-Kyoto (WKY) rat strains.(2) Here, we extend our analysis of this cross by adding new genetic markers, now defining a 10 cM interval on rat chromosome 8 associated with ambulatory and exploratory activities. Then we present a replication of this QTL detection, at least for exploratory activity, by a new genetic mapping analysis of an activity QTL in an F2 cross between the WKHA and Brown Norway (BN) rat strains. Overall, the results provide compelling evidence for the presence of gene(s) influencing activity at this locus. The QTL interval has been refined such that the human orthologous region could be defined and tested in human populations for association with ADHD. Ultimately, the improved dissection of this genomic locus should allow the identification of the causal genes.

  20. Small interfering RNA therapy against carbohydrate sulfotransferase 15 inhibits cardiac remodeling in rats with dilated cardiomyopathy.

    PubMed

    Watanabe, Kenichi; Arumugam, Somasundaram; Sreedhar, Remya; Thandavarayan, Rajarajan A; Nakamura, Takashi; Nakamura, Masahiko; Harima, Meilei; Yoneyama, Hiroyuki; Suzuki, Kenji

    2015-07-01

    Carbohydrate sulfotransferase 15 (CHST15) is a sulfotransferase responsible for biosynthesis of chondroitin sulfate E (CS-E), which plays important roles in numerous biological events such as biosynthesis of proinflammatory cytokines. However, the effects of CHST15 siRNA in rats with chronic heart failure (CHF) after experimental autoimmune myocarditis (EAM) have not yet been investigated. CHF was elicited in Lewis rats by immunization with cardiac myosin, and after immunization, the rats were divided into two groups and treated with either CHST15 siRNA (2μg/week) or vehicle. Age matched normal rats without immunizations were also included in this study. After 7weeks of treatment, we investigated the effects of CHST15 siRNA on cardiac function, proinflammatory cytokines, and cardiac remodeling in EAM rats. Myocardial functional parameters measured by hemodynamic and echocardiographic studies were significantly improved by CHST15 siRNA treatment in rats with CHF compared with that of vehicle-treated CHF rats. CHST15 siRNA significantly reduced cardiac fibrosis, and hypertrophy and its marker molecules (left ventricular (LV) mRNA expressions of transforming growth factor beta1, collagens I and III, and atrial natriuretic peptide) compared with vehicle-treated CHF rats. CHF-induced increased myocardial mRNA expressions of proinflammatory cytokines [interleukin (IL)-6, IL-1β], monocyte chemoattractant protein-1, and matrix metalloproteinases (MMP-2 and -9), and CHST15 were also suppressed by the treatment with CHST15 siRNA. Western blotting study has confirmed the results obtained from mRNA analysis as CHST15 siRNA treated rats expressed reduced levels of inflammatory and cardiac remodeling marker proteins. Our results demonstrate for the first time, that CHST15 siRNA treatment significantly improved LV function and ameliorated the progression of cardiac remodeling in rats with CHF after EAM.

  1. Renal handling of sodium and water in the hypothyroid rat

    PubMed Central

    Michael, Ulrich F.; Barenberg, Robert L.; Chavez, Rafaelita; Vaamonde, Carlos A.; Papper, Solomon

    1972-01-01

    Hypothyroid rats were examined with conventional renal clearance and micropuncture techniques to elicit the mechanism and site within the nephron responsible for the increased salt and water excretion observed in these animals. When compared with age-matched control rats, a decrease in inulin clearance of 30% (P < 0.001) and in Hippuran clearance of 32% (P < 0.005) was observed in the hypothyroid rats. Absolute excretion of sodium and water was increased 3-fold (P < 0.02) and 2-fold (P < 0.025), respectively, while fractional excretion of sodium and water was increased 4.3-fold (P < 0.02) and 2.9-fold (P < 0.05), respectively, in the hypothyroid animals. Fractional proximal reabsorption of sodium as assessed from proximal tubular fluid to plasma ratios of inulin ([TF/P]IN) was found to be decreased by 28% (P < 0.001) in the hypothyroid rats. Superficial single nephron filtration rate was reduced proportionately to the decrease in total filtration rate in the hypothyroid rats. These data indicate that the proximal tubule is one of the sites of diminished sodium and water reabsorption in the hypothyroid rat. The data also suggest that the observed decrease in glomerular filtration rate in the hypothyroid animals is not caused by a decrease in the number of functioning nephrons and that the observed increase in sodium and water excretion is not caused by a redistribution of filtrate from juxtamedullary to superficial nephrons. Although the exact mechanisms of the observed changes in proximal tubular function remain unknown, the data suggest that they are probably related to the lack of thyroid hormone. Whatever their mechanism, it appears that the enhanced sodium and water excretion observed in the hypothyroid animals must be determined by further reduction in tubular sodium reabsorption in the distal nephron. PMID:5024038

  2. Quantitative proteome of medulla oblongata in spontaneously hypertensive rats.

    PubMed

    Sun, Dongmei; Cheng, Yu; Zhou, Danfeng; Liu, Tanshu; Chen, Shaoqin; Liang, Jing; Tang, Chunzhi; Lai, Xinsheng

    2013-01-04

    We performed an extensive quantitative proteomic analysis on the pooled medulla sample of the 11-week-old spontaneously hypertensive rats (SHR) compared to age-matched normotensive Wistar rats, using iTRAQ technology coupled with nano two-dimentional liquid chromatography followed by high resolution mass spectrometric abundance indexes techniques. Many differentially expressed proteins identified were involved in energy metabolism, such as mitochondrial part, pyruvate dehydrogenase complex, and respiratory chain. These proteins were included in citrate cycle (TCA cycle), pyruvate metabolism and oxidative phosphorylation. The proteomic analysis and subsequent Western blotting on two independent cohorts of animials indicated that the dysregulation of energy metabolism existed in the medulla of the SHR rats. The differentially expressed proteins in the dysregulation of energy metabolism in the medulla of SHR rats included down-regulated ATP6V1D, ATP6VOA1, ATP5L, DLD proteins and up-regulated AK1 protein. MAO-A protein also exhibited decreased regulation, as well as the other 3 above-mentioned energy-relative proteins (ATP6V1D, ATP5L and DLD proteins) belonging to the heterocycle metabolic process. A receiver operating characteristic curve (ROC) analysis on 4 of the differentially expressed proteins respectively resulted in an area under the receiver operating characteristic curve (AUC) of 0.95, 0.90, 0.92, and 0.81 for differentiating the SHR rats from the normotensive rats. This dysfunction in energy metabolism localizes to the medulla, the lower part of brain stem, and is, therefore, likely to contribute to the development, as well as to pathophysiological complications of hypertension.

  3. Lower risk taking and exploratory behavior in alcohol-preferring sP rats than in alcohol non-preferring sNP rats in the multivariate concentric square field (MCSF) test.

    PubMed

    Roman, Erika; Colombo, Giancarlo

    2009-12-14

    The present investigation continues previous behavioral profiling studies of selectively bred alcohol-drinking and alcohol non-drinking rats. In this study, alcohol-naïve adult Sardinian alcohol-preferring (sP) and non-preferring (sNP) rats were tested in the multivariate concentric square field (MCSF) test. The MCSF test has an ethoexperimental approach and measures general activity, exploration, risk assessment, risk taking, and shelter seeking in laboratory rodents. The multivariate design enables behavioral profiling in one and the same test situation. Age-matched male Wistar rats were included as a control group. Five weeks after the first MCSF trial, a repeated testing was done to explore differences in acquired experience. The results revealed distinct differences in exploratory strategies and behavioral profiles between sP and sNP rats. The sP rats were characterized by lower activity, lower exploratory drive, higher risk assessment, and lower risk taking behavior than in sNP rats. In the repeated trial, risk-taking behavior was almost abolished in sP rats. When comparing the performance of sP and sNP rats with that of Wistar rats, the principal component analysis revealed that the sP rats were the most divergent group. The vigilant behavior observed in sP rats with low exploratory drive and low risk-taking behavior is interpreted here as high innate anxiety-related behaviors and may be related to their propensity for high voluntary alcohol intake and preference. We suggest that the different lines of alcohol-preferring rats with different behavioral characteristics constitute valuable animal models that mimic the heterogeneity in human alcohol dependence.

  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. 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

  6. Activation of retinal stem cells in the proliferating marginal region of RCS rats during development of retinitis pigmentosa.

    PubMed

    Jian, Qian; Xu, Haiwei; Xie, Hanping; Tian, Chunyu; Zhao, Tongtao; Yin, ZhengQin

    2009-11-06

    Retinal stem cells (RSCs) have been demonstrated at the proliferating marginal regions from the pars plana of ciliary body to the ciliary marginal zone (CMZ) in adult lower vertebrates and mammals. Investigations in the lower vertebrates have provided some evidence that RSCs can proliferate following retinal damage; however, the evidence that this occurs in mammals is not clear. In this study, we explored RSCs proliferation potential of adult mammalian in proliferating marginal regions of Royal College of Surgeons (RCS) rats, an animal model for retinitis pigmentosa (RP). The proliferation was evaluated using BrdU labeling, and Chx-10 as markers to discern progenitor cell of CMZ in Long-Evan's and RCS rats at different postnatal day (PND) after eye opening. We found that few Chx-10 and BrdU labeled cells in the proliferating marginal regions of Long-Evan's rats, which significantly increased in RCS rats at PND30 and PND60. Consistent with this, Chx-10/Vimentin double staining cells in the center retina of RCS rats increased significantly at PND30 after eye opening. In addition, mRNA expression of Shh, Ptch1 and Smo was up-regulated in RCS rats at PND60 compared to age-matched Long-Evan's rats, which revealed Shh/ptc pathway involving in the activation of RSCs. These results suggest that RSCs in the mammalian retinal proliferating marginal regions has the potential to regenerate following degeneration.

  7. TRPV1 attenuates intracranial arteriole remodeling through inhibiting VSMC phenotypic modulation in hypertension.

    PubMed

    Zhang, Ming-Jie; Liu, Yun; Hu, Zi-Cheng; Zhou, Yi; Pi, Yan; Guo, Lu; Wang, Xu; Chen, Xue; Li, Jing-Cheng; Zhang, Li-Li

    2017-04-01

    The phenotypic modulation of contractile vascular smooth muscle cell (VSMC) is widely accepted as the pivotal process in the arterial remodeling induced by hypertension. This study aimed to investigate the potential role of transient receptor potential vanilloid type 1 (TRPV1) on regulating VSMC plasticity and intracranial arteriole remodeling in hypertension. Spontaneously hypertensive rats (SHR), Wistar-Kyoto (WKY) rats and TRPV1(-/-) mice on a C57BL/6J background were used. By microscopic observation of the histopathological sections of vessels from hypertensive SHR and age-matched normotensive WKY control rats, we found that hypertension induced arterial remodeling. Decreased α-smooth muscle actin (α-SMA) and SM22α while increased osteopontin (OPN) were observed in aorta and VSMCs derived from SHR compared with those in WKY, and VSMCs derived from SHR upregulated inflammatory factors. TRPV1 activation by capsaicin significantly increased expression of α-SMA and SM22α, reduced expression of OPN, retarded proliferative and migratory capacities and inhibited inflammatory status in VSMCs from SHR, which was counteracted by TRPV1 antagonist 5'-iodoresiniferatoxin (iRTX) combined with capsaicin. TRPV1 activation by capsaicin ameliorated intracranial arteriole remodeling in SHR and deoxycorticosterone acetate (DOCA)-salt hypertensive mice. However, the attenuation of arteriole remodeling by capsaicin was not observed in TRPV1(-/-) mice. Furthermore, TRPV1 activation significantly decreased the activity of PI3K and phosphorylation level of Akt in SHR-derived VSMCs. Taken together, we provide evidence that TRPV1 activation by capsaicin attenuates intracranial arteriole remodeling through inhibiting VSMC phenotypic modulation during hypertension, which may be at least partly attributed to the suppression PI3K/Akt signaling pathway. These findings highlight the prospect of TRPV1 in prevention and treatment of hypertension.

  8. Enhanced expression of Gqα and PLC-β1 proteins contributes to vascular smooth muscle cell hypertrophy in SHR: role of endogenous angiotensin II and endothelin-1.

    PubMed

    Atef, Mohammed Emehdi; Anand-Srivastava, Madhu B

    2014-07-01

    Vascular Gqα signaling has been shown to contribute to cardiac hypertrophy. In addition, angiotensin II (ANG II) was shown to induce vascular smooth muscle cell (VSMC) hypertrophy through Gqα signaling; however, the studies on the role of Gqα and PLC-β1 proteins in VSMC hypertrophy in animal model are lacking. The present study was therefore undertaken to examine the role of Gqα/PLC-β1 proteins and the signaling pathways in VSMC hypertrophy using spontaneously hypertensive rats (SHR). VSMC from 16-wk-old SHR and not from 12-wk-old SHR exhibited enhanced levels of Gqα/PLC-β1 proteins compared with age-matched Wistar-Kyoto (WKY) rats as determined by Western blotting. However, protein synthesis as determined by [(3)H]leucine incorporation was significantly enhanced in VSMC from both 12- and 16-wk-old SHR compared with VSMC from age-matched WKY rats. Furthermore, the knockdown of Gqα/PLC-β1 in VSMC from 16-wk-old SHR by antisense and small interfering RNA resulted in attenuation of protein synthesis. In addition, the enhanced expression of Gqα/PLC-β1 proteins, enhanced phosphorylation of ERK1/2, and enhanced protein synthesis in VSMC from SHR were attenuated by the ANG II AT1 and endothelin-1 (ET-1) ETA receptor antagonists losartan and BQ123, respectively, but not by the ETB receptor antagonist BQ788. In addition, PD98059 decreased the enhanced expression of Gqα/PLC-β1 and protein synthesis in VSMC from SHR. These results suggest that the enhanced levels of endogenous ANG II and ET-1 through the activation of AT1 and ETA receptors, respectively, and MAP kinase signaling, enhanced the expression of Gqα/PLC-β1 proteins in VSMC from 16-wk-old SHR and result in VSMC hypertrophy.

  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. Cocaine- and amphetamine-regulated transcript (CART) peptide immunoreactivity in feeding- and reward-related brain areas of young OLETF rats.

    PubMed

    Armbruszt, Simon; Abraham, Hajnalka; Figler, Maria; Kozicz, Tamas; Hajnal, Andras

    2013-05-01

    Cocaine- and amphetamine-regulated transcript (CART) peptide is expressed in brain areas involved in the control of appetite, drug reward and homeostatic regulation and it has an overall anorexigenic effect. Recently, we have shown that CART peptide immunoreactivity was significantly reduced in the rostral part of the nucleus accumbens and in the rostro-medial part of the nucleus of the solitary tract in adult CCK-1 receptor deficient obese diabetic Otsuka Long Evans Tokushima Fatty (OLETF) rats compared to Long Evans Tokushima Otsuka (LETO) lean controls. It is not clear, however, whether altered CART expression is caused primarily by the deficiency in CCK-1 signaling or whether is related to the obese and diabetic phenotype of the OLETF strain which develops at a later age. Therefore, in the present study, CART-immunoreaction in feeding-related areas of the brain was compared in young, age-matched (6-7 weeks old) non-obese, non-diabetic OLETF rats and in LETO controls. We found that, young, non-diabetic OLETF rats revealed unaltered distribution of CART-peptide expressing neurons and axons throughout the brain when compared to age-matched LETO rats. In contrast to previous results observed in the obese diabetic adult rats, intensity of CART immunoreaction did not differ in the areas related to control of food-intake and reward in the young OLETFs compared to young LETO rats. Our findings suggest that factors secondary to obesity and/or diabetes rather than impaired CCK-1 receptor signaling may contribute to altered CART expression in the OLETF strain.

  11. Prolonged water immersion. Effects on blood pressure maturation in normotensive rats.

    PubMed

    Magrini, F; Reggiani, P; Ciulla, M; Meazza, R; Branzi, G

    1992-05-01

    The purpose of this experiment was to study the impact of simulated microgravity and of chronic removal of hydrostatic pressure gradients on blood pressure maturation and body growth in rats. A special device was developed in our laboratory to transfer prolonged "dry" water immersion (a technique that has been used for training astronauts under hypogravic conditions) to six Sprague-Dawley test rats (immersion-G group). The time course of heart rate, systolic blood pressure, urinary output, and body weight was monitored from weaning to maturity and then compared with those responses from six sex- and age-matched Sprague-Dawley rats grown in a gravity environment (group G). A downward shift in systolic blood pressure and body weight maturation curves was observed in immersion-G rats from the age of 60 days. Cessation of dry water immersion produced a gradual, significant rise in systolic blood pressure but not in body weight to control values. No marked changes in heart rate and urinary output between G and immersion-G rats were noticed throughout the investigation. Our results provide indirect evidence that an interference in the natural history of blood pressure maturation was introduced by immersion, which dissociated the effects of body weight increase during growth from the effects of ageing per se. It is concluded that the physiological increase in systolic blood pressure during growth is partly gravity-dependent.

  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. 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

  14. Diabetes Enhances Dental Caries and Apical Periodontitis in Caries-Susceptible WBN/KobSlc Rats

    PubMed Central

    Kodama, Yasushi; Matsuura, Masahiro; Sano, Tomoya; Nakahara, Yutaka; Ozaki, Kiyokazu; Narama, Isao; Matsuura, Tetsuro

    2011-01-01

    Many epidemiologic studies have suggested that diabetes may be an important risk factor for periodontal disease. To determine whether diabetes induces or enhances periodontal disease or dental caries, dental tissue from diabetic male and nondiabetic female WBN/KobSlc rats and male and female age-matched nondiabetic F344 rats was analyzed morphologically and morphometrically for these 2 types of lesions. Soft X-ray examination revealed that the incidence and severity of both molar caries and alveolar bone resorption were much higher in male WBN/KobSlc rats with chronic diabetes than in nondiabetic female rats of the same strain. Histopathologic examination showed that dental caries progressed from acute to subacute inflammation due to bacterial infections and necrosis in the pulp when the caries penetrated the dentin. In the most advanced stage of dental caries, inflammatory changes caused root abscess and subsequent apical periodontitis, with the formation of granulation tissue around the dental root. Inflammatory changes resulted in resorption of alveolar bone and correlated well with the severity of molar caries. Our results suggest that diabetic conditions enhance dental caries in WBN/KobSlc rats and that periodontal lesions may result from the apical periodontitis that is secondary to dental caries. PMID:21819682

  15. Reduced Activity of the Aortic Gamma-Glutamyltransferase Does Not Decrease S-Nitrosoglutathione Induced Vasorelaxation of Rat Aortic Rings

    PubMed Central

    Perrin-Sarrado, Caroline; Pongas, Marios; Dahboul, Fatima; Leroy, Pierre; Pompella, Alfonso; Lartaud, Isabelle

    2016-01-01

    Aims: Gamma-glutamyl transferase (GGT), an enzyme present on the endothelium, is involved in the release of nitric oxide (NO) from S-nitrosoglutathione (GSNO) and in the GSNO-induced vasodilation. Endogenous GSNO is a physiological storage form of NO in tissues while exogenous GSNO is an interesting candidate for compensating for the decreased NO bioavailability occurring during cardiovascular diseases. We investigated in a rat model of human hypertension, the spontaneous hypertensive rat (SHR), submitted or not to high salt diet, whether a decreased vascular GGT activity modifies the vasorelaxant effect of GSNO. Methods: Thoracic aortic rings isolated from male SHR and Wistar Kyoto rats (WKY) aged 20–22 weeks—submitted or not for 8 weeks to a high salt diet (1% w/v NaCl in drinking water) were pre-constricted with phenylephrine then submitted to concentration-vasorelaxant response curves (maximal response: Emax; pD2) to carbachol or sodium nitroprusside to evaluate endothelial dependent or independent NO-induced vasodilation, or GSNO (exogenous NO vasodilation depending from the endothelial GGT activity). GGT activity was measured using a chromogenic substrate in aortic homogenates. Its role in GSNO-induced relaxation was assessed following inhibition of the enzyme activity (serine-borate complex). That of protein disulfide isomerase (PDI), another redox sensitive enzyme involved in GSNO metabolism, was assessed following inhibition with bacitracin. Results: Aortic GGT activity (18–23 μmol/min/mg of tissue in adult WKY) decreased by 33% in SHR and 45% in SHR with high salt diet. Emax and pD2 for sodium nitroprusside were similar in all groups. Emax for carbachol decreased by −14%, reflecting slight endothelial NO-dependent dysfunction. The GSNO curve was slightly shifted to the left in SHR and in SHR with high salt diet, showing a small enhanced sensitivity to GSNO. Involvements of GGT, as that of PDI, in the GSNO effects were similar in all groups (pD2

  16. Downregulation of microRNA-34b is responsible for the elevation of blood pressure in spontaneously hypertensive rats

    PubMed Central

    Yang, Fan; Li, Haiyu; Du, Youyou; Shi, Qiangwei; Zhao, Luosha

    2017-01-01

    The present study aimed to identify the microRNA (miRNA) responsible for the development of primary hypertension, and examine the downstream signaling pathway, which mediates the effect of the miRNA. Reverse transcription-quantitative polymerase chain reaction analysis was performed to identify which miRNA may be involved in the pathogenesis of hypertension. In silico analysis and a luciferase assay were used to validate the target of the selected miRNA, and miRNA mimics and small interfering (si)RNA of the target were transfected into smooth muscle cells to examine its effect on the biological activity of the cells. miR-34b was found to be upregulated in spontaneously hypertensive rats (SHRs), compared with Wistar Kyoto (WKY) rats. Therefore, the present study used online miRNA target prediction tools to predict the candidate target genes of miR-34b in the database, and consequently identified cyclin G1 (CCNG1) and cyclin-dependent kinase 6 (CDK6) as its possible target genes. CDK6 subsequently identified to be the direct target gene of miR-34b using a luciferase reporter assay in vascular smooth muscle cells (VSMCs). The present study also established the possible negative regulatory association between miR-34b and CDK6 via investigating the mRNA and protein expression levels of CDK6 and CCNG1 in VSMCs collected from the SHRs and WKY rats, respectively. To investigate the signaling pathways between miR-34b and CDK6, the mRNA and protein expression levels of CDK6, and the proliferation rates were compared in VSMCs transfected with CDK6 siRNA or miR-34b mimics, the results of which indicated that the miR-34b mimics exerted the same effects on the expression of CDK6 and cell proliferation as CDK6 siRNA. The negative regulatory association between miR-34b and its target, CDK6, was confirmed, which may offer potential as a novel therapeutic target in the treatment of hypertension. PMID:28098882

  17. Genetic mapping of two blood pressure quantitative trait loci on rat chromosome 1.

    PubMed Central

    Gu, L; Dene, H; Deng, A Y; Hoebee, B; Bihoreau, M T; James, M; Rapp, J P

    1996-01-01

    A genetic map for rat chromosome 1 was constructed using 66 microsatellite markers typed on either or both of two populations derived from inbred Dahl salt-sensitive (S) rats: F2(LEW x S) n = 151, and F2(WKY x S) n = 159. These populations had been raised on a high salt (8% NaCl) diet. Systolic blood pressure and heart weight were found to be genetically linked to two separate regions on rat chromosome 1 in the F2(LEW x S) population. One region was centered around the anonymous SA locus and accounted for 24 mmHg of blood pressure. The other region was 55 cM from the SA locus centered around a cluster of cytochromes P450 loci, and accounted for 30 mmHg of blood pressure. Since blood pressure and heart weight were highly correlated these same regions were also linked to heart weight. These results were cross-specific as linkage of these chromosome 1 regions to blood pressure and heart weight was not observed in several other F2 populations derived by crossing S and other normotensive control strains. This is presumably due to different alleles and/or different genetic backgrounds in the various populations. The SA region of chromosome 1 was found to influence body weight in F2(LEW x S) rats. Combining the present data with our previously published data on the F2(LEW x S) population showed that four separate quantitative trait loci with additive effects accounted for 106 mmHg and 38% of the total variance of blood pressure and for 506 mg and 34% of the total variance of heart wt. PMID:8609235

  18. Immuno-neutralization of circulating relaxin does not alter the breast cancer-protective action of parity in MNU-treated rats.

    PubMed

    Steinetz, Bernard G; Sherwood, O David; Lasano, Sally; Horton, Lori; Bosland, Maarten C

    2004-04-01

    Early pregnancy and childbirth protects women against future development of breast cancer by an unknown mechanism. Parity likewise reduces mammary cancer incidence in rats exposed to the carcinogen, N-methyl-N-nitrosourea (MNU), providing a model for the human phenomenon. We hypothesized that relaxin, a 6KD luteal mammotropic hormone of pregnancy, might be the anti-cancer pregnancy factor, and that induced relaxin deficiency during rat gestation would restore carcinogen sensitivity. Forty-one pregnant (age 50 days) and 25 age-matched virgin Sprague-Dawley rats were used. Relaxin deficiency was induced by injecting mouse monoclonal anti-rat relaxin antibody (MCA1) days 12-18 of gestation. Pregnant controls were injected with vehicle or mouse IgG on the same schedule. Because MCA1 disrupts parturition, all rats underwent cesarean section on day 22. At age 100 days, all rats were injected i.v. with MNU (50mg/Kg) and examined daily for tumors until euthanized at age 240 days. Mammary tumor incidence and frequency were significantly (p<0.01) reduced and tumor latency was increased (p<0.001) in primiparous as compared with virgin rats. However, tumor incidence, type, size and latency were similar in MCA1-treated and control primiparous rats. Thus, luteal relaxin does not appear to be the factor responsible for resistance to breast cancer.

  19. Transthoracic echocardiography in rats. Evalution of commonly used indices of left ventricular dimensions, contractile performance, and hypertrophy in a genetic model of hypertrophic heart failure (SHHF-Mcc-facp-Rats) in comparison with Wistar rats during aging.

    PubMed

    Reffelmann, Thorsten; Kloner, Robert A

    2003-09-01

    Two-weekly echocardiographic examinations were conducted in nine SHHF-Mc-fa(cp) rats in comparison with eight age-matched Wistar rats. In the SHHF-rats, characterized by progressive LV-dilation and decreasing contractile function between 77-87 weeks of age, left ventricular (LV) hypertrophy was most sensitively demonstrated by increased LV-mass-index (p < 0.001). LV-areas and area-ejection fraction (EF) (2D-images) discriminated more sensitively in the early stages than M-mode-derived diameters and fractional shortening (FS); midwall shortening was the most sensitive parameter of reduced systolic function. Post-mortem measurements showed an excellent correlation with calculated LV-mass (r = 0.91). Post-mortem LV-volumes correlated significantly with diastolic LV-diameters, LV-areas, and calculated LV-volumes (r = 0.56-0.59). Mean within-subject standard deviations in controls were 0.5-0.6 mm (LV-diameters), 3.1-4.6 mm(2) (LV-areas), approximately 10% of the mean for FS, area-EF and midwall shortening, and approximately 20% for wall thickness and LV-mass. The data might be used to choose the most sensitive parameters, and to estimate sample size for echocardiographic investigations in rats.

  20. Reproductive experience reduces circulating 17beta-estradiol and prolactin levels during proestrus and alters estrogen sensitivity in female rats.

    PubMed

    Bridges, Robert S; Byrnes, Elizabeth M

    2006-05-01

    The reproductive experiences of pregnancy, parturition, and lactation affect a range of neural and endocrine processes after the end of lactation. In women, previous parity results in reduced circulating prolactin (PRL) and androgen levels years after giving birth. Reductions in PRL secretion also occur in reproductively experienced, female rats. In the present study we examined the status and regulation of estradiol (E(2)) and PRL during the reproductive cycle after reproductive experience. These hormones regulate one another and have been implicated in a number of disease and aging processes. Using a rat model, the patterns of E(2) and PRL secretion, pituitary PRL content, and estrogen receptor alpha expression were characterized from 1200-1800 h on proestrus in age-matched, primiparous and nulliparous animals. The possible effect of parity on estrogen sensitivity was then examined by challenging nonlactating, ovariectomized, age-matched, multiparous and nulliparous rats with estradiol benzoate (EB; 0, 1, 5, 25, and 125 microg/kg) and measuring PRL responses 24 and 48 h later. Previous parity resulted in modest, yet significant, reductions in E(2) and PRL levels on proestrus, a limited increase in pituitary estrogen receptor alpha expression, and a significant shift in estrogen sensitivity, as measured by EB-induced PRL secretion. Nulliparous animals were more sensitive than multiparous rats to the two lower doses of EB, whereas multiparous animals were more responsive to the highest EB dose. These unique parity-induced alterations in the female's endocrine state that persist beyond lactation may impact a multitude of estrogen-mediated processes over the female's adult life span.

  1. 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

  2. Arrest in ciliated cell expansion on the bronchial lining of adult rats caused by chronic exposure to industrial noise.

    PubMed

    Oliveira, Maria João R; Pereira, António S; Ferreira, Paula G; Guimarães, Laura; Freitas, Diamantino; Carvalho, António P O; Grande, Nuno R; Aguas, Artur P

    2005-03-01

    Workers chronically exposed to high-intensity/low-frequency noise at textile plants show increased frequency of respiratory infections. This phenomenon prompted the herein investigation on the cytology of the bronchial epithelium of Wistar rats submitted to textile noise. Workplace noise from a cotton-mill room of a textile factory was recorded and reproduced in a sound-insulated animal room. The Wistar rats were submitted to a weekly schedule of noise treatment that was similar to that of the textile workers (8h/day, 5 days/week). Scanning electron microscopy (SEM) was used to compare the fine morphology of the inner surface of the bronchi in noise-exposed and control rats. SEM quantitative cytology revealed that exposure to noise for 5-7 months caused inhibition in the natural expansion of the area occupied by ciliated cells on the bronchial epithelium as adult rats grow older. This difference between noise-exposed and age-matched control rats was statistically significant (P<0.05) and documents that the cytology of the rat bronchial epithelium is mildly altered by noise exposure. The decrease in the area of bronchial cilia may impair the mucociliar clearance of the respiratory airways and, thus, increase vulnerability to respiratory infection.

  3. The calcium channel antagonist benidipine reduces plasma and cardiac endothelin-1 levels in type II diabetic rat model.

    PubMed

    Jesmin, Subrina; Sakuma, Ichiro; Hattori, Yuichi; Kitabatake, Akira; Miyauchi, Takashi

    2004-11-01

    Cardiovascular complications are the central feature of type 2 diabetes mellitus, and insulin resistance is an early clinical manifestation of type 2 diabetes mellitus. Calcium channel blockers are widely used to treat cardiovascular diseases in diabetic patients; however, it remains unknown how endothelin-1 (ET-1) is altered and associated with cardiac lesions at the insulin-resistant early stage of type 2 diabetes mellitus, and, if so, whether calcium channel blockers can reverse such alterations. We examined plasma and cardiac expression of ET-1 in male Otsuka Long-Evans Tokushima Fatty (OLETF) rats, a spontaneous model of human type 2 diabetes mellitus. At 8 weeks of age, OLETF rats were treated for 12 weeks with a long acting calcium channel blocker, benidipine (3 mg/kg per day p.o.) (BEN, n = 15), or with vehicle (OLETF, n = 15), and age-matched genetic control, male Long-Evans Tokushima Otsuka (LETO) rats were also used (n = 15). Blood pressure was significantly higher in OLETF than LETO rats, and benidipine treatment of OLETF rats for 12 weeks did not reduce their blood pressure significantly. Plasma and cardiac levels of ET-1 were significantly higher in OLETF compared with LETO rats (both P < 0.01), and were reversed after benidipine treatment. Our results suggest that ET-1 plays a pivotal role in the pathogenesis of cardiac complications at the insulin-resistant stage of diabetes mellitus, and that benidipine treatment may have a beneficial effect on these complications.

  4. Kinematics of treadmill locomotion in rats conceived, born, and reared in a hypergravity field (2 g). Adaptation to 1 g.

    PubMed

    Bouët, V; Borel, L; Harlay, F; Gahéry, Y; Lacour, M

    2004-04-02

    The kinematics of treadmill locomotion in rats conceived, born, and raised in a hypergravity environment (HG: 2g) until the age of 3 months was investigated for 5 weeks after their exposition to earth's gravity. The locomotor performance of the HG rats (N=7) was compared to that of age-matched control rats (N=8) housed at 1g for the same period. Kinematic analysis of treadmill locomotion was performed up to 35 days of terrestrial life by an optoelectronic motion analyzer (ELITE system). Results showed that the HG rats exhibited a faster locomotor rhythm (increased number of steps/s), walked closer to the ground, and had a more dorsiflexed foot position. Also, HG rats had shorter steps. The data also highlight a fast adaptation to normal gravity since all the locomotor parameters returned to normal values within 3 weeks. The locomotor modifications may be seen as the persistence of a hypergravity-induced posturo-locomotor adaptation in the centrifuge and/or to more functional changes of sensorimotor systems. Because locomotor performance of HG rats is not severely affected, it is concluded that early development of locomotion processes is highly resistant to gravito-inertial changes.

  5. Melatonin, given at the time of reperfusion, prevents ventricular arrhythmias in isolated hearts from fructose-fed rats and spontaneously hypertensive rats.

    PubMed

    Diez, Emiliano Raúl; Renna, Nicolás Federico; Prado, Natalia Jorgelina; Lembo, Carina; Ponce Zumino, Amira Zulma; Vazquez-Prieto, Marcela; Miatello, Roberto Miguel

    2013-09-01

    Melatonin reduces reperfusion arrhythmias when administered before coronary occlusion, but in the clinical context of acute coronary syndromes, most of the therapies are administered at the time of reperfusion. Patients frequently have physiological modifications that can reduce the response to therapeutic interventions. This work determined whether acute melatonin administration starting at the moment of reperfusion protects against ventricular arrhythmias in Langendorff-perfused hearts isolated from fructose-fed rats (FFR), a dietary model of metabolic syndrome, and from spontaneous hypertensive rats (SHR). In both experimental models, we confirmed metabolic alterations, a reduction in myocardial total antioxidant capacity and an increase in arterial pressure and NADPH oxidase activity, and in FFR, we also found a decrease in eNOS activity. Melatonin (50 μm) initiated at reperfusion after 15-min regional ischemia reduced the incidence of ventricular fibrillation from 83% to 33% for the WKY strain, from 92% to 25% in FFR, and from 100% to 33% in SHR (P = 0.0361, P = 0.0028, P = 0.0013, respectively, by Fisher's exact test, n = 12 each). Although, ventricular tachycardia incidence was high at the beginning of reperfusion, the severity of the arrhythmias progressively declined in melatonin-treated hearts. Melatonin induced a shortening of the action potential duration at the beginning of reperfusion and in the SHR group also a faster recovery of action potential amplitude. We conclude that melatonin protects against ventricular fibrillation when administered at reperfusion, and these effects are maintained in hearts from rats exposed to major cardiovascular risk factors. These results further support the ongoing translation to clinical trials of this agent.

  6. Variability in ozone-induced pulmonary injury and inflammation in healthy and cardiovascular-compromised rat models.

    PubMed

    Kodavanti, Urmila P; Ledbetter, Allen D; Thomas, Ronald F; Richards, Judy E; Ward, William O; Schladweiler, Mette C; Costa, Daniel L

    2015-01-01

    The molecular bases for variability in air pollutant-induced pulmonary injury due to underlying cardiovascular (CVD) and/or metabolic diseases are unknown. We hypothesized that healthy and genetic CVD-prone rat models will exhibit exacerbated response to acute ozone exposure dependent on the type and severity of disease. Healthy male 12-14-week-old Wistar Kyoto (WKY), Wistar (WS) and Sprague Dawley (SD); and CVD-compromised spontaneously hypertensive (SH), Fawn-Hooded hypertensive (FHH), stroke-prone spontaneously hypertensive (SHSP), obese spontaneously hypertensive heart failure (SHHF) and obese JCR (JCR) rats were exposed to 0.0, 0.25, 0.5, or 1.0 ppm ozone for 4 h; pulmonary injury and inflammation were analyzed immediately following (0-h) or 20-h later. Baseline bronchoalveolar lavage fluid (BALF) protein was higher in CVD strains except for FHH when compared to healthy. Ozone-induced increases in protein and inflammation were concentration-dependent within each strain but the degree of response varied from strain to strain and with time. Among healthy rats, SD were least affected. Among CVD strains, lean rats were more susceptible to protein leakage from ozone than obese rats. Ozone caused least neutrophilic inflammation in SH and SHHF while SHSP and FHH were most affected. BALF neutrophils and protein were poorly correlated when considering the entire dataset (r = 0.55). The baseline and ozone-induced increases in cytokine mRNA varied markedly between strains and did not correlate with inflammation. These data illustrate that the degree of ozone-induced lung injury/inflammation response is likely influenced by both genetic and physiological factors that govern the nature of cardiovascular compromise in CVD models.

  7. 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

  8. Autophagic signaling and proteolytic enzyme activity in cardiac and skeletal muscle of spontaneously hypertensive rats following chronic aerobic exercise.

    PubMed

    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.

  9. Precision-cut liver slices from diet-induced obese rats exposed to ethanol are susceptible to oxidative stress and increased fatty acid synthesis.

    PubMed

    Duryee, Michael J; Willis, Monte S; Schaffert, Courtney S; Reidelberger, Roger D; Dusad, Anand; Anderson, Daniel R; Klassen, Lynell W; Thiele, Geoffrey M

    2014-02-01

    Oxidative stress from fat accumulation in the liver has many deleterious effects. Many believe that there is a second hit that causes relatively benign fat accumulation to transform into liver failure. Therefore, we evaluated the effects of ethanol on ex vivo precision-cut liver slice cultures (PCLS) from rats fed a high-fat diet resulting in fatty liver. Age-matched male Sprague-Dawley rats were fed either high-fat (obese) (45% calories from fat, 4.73 kcal/g) or control diet for 13 mo. PCLS were prepared, incubated with 25 mM ethanol for 24, 48, and 72 h, harvested, and evaluated for ethanol metabolism, triglyceride production, oxidative stress, and cytokine expression. Ethanol metabolism and acetaldehyde production decreased in PCLS from obese rats compared with age-matched controls (AMC). Increased triglyceride and smooth muscle actin production was observed in PCLS from obese rats compared with AMC, which further increased following ethanol incubation. Lipid peroxidation, measured by thiobarbituric acid reactive substances assay, increased in response to ethanol, whereas GSH and heme oxygenase I levels were decreased. TNF-α and IL-6 levels were increased in the PCLS from obese rats and increased further with ethanol incubation. Diet-induced fatty liver increases the susceptibility of the liver to toxins such as ethanol, possibly by the increased oxidative stress and cytokine production. These findings support the concept that the development of fatty liver sensitizes the liver to the effects of ethanol and leads to the start of liver failure, necrosis, and eventually cirrhosis.

  10. Antihypertensive and Antihypertrophic Effects of Acupuncture at PC6 Acupoints in Spontaneously Hypertensive Rats and the Underlying Mechanisms

    PubMed Central

    Xin, Juan-Juan; Gao, Jun-Hong; Wang, Yuan-Yuan; Lu, Feng-Yan; Zhao, Yu-Xue; Jing, Xiang-Hong

    2017-01-01

    The aim of this work is to investigate the effect of electroacupuncture (EA) at PC6 on the hypertension and myocardial hypertrophy in spontaneously hypertensive rats (SHRs). Thirty SHRs were randomized into model, SHR + EA, and SHR + Sham EA group with WKY rats as normal control. EA was applied once a day in 8 consecutive weeks. The blood pressure (BP), cardiac function, and hypertrophy as well as the underlying mechanisms were investigated. After EA treatment, the enhanced BP in SHR + EA group was significantly lower compared to both the period before EA and model group. Echocardiographic, morphological studies showed that the enhanced left ventricular anterior and posterior wall end-diastolic (LVAWd and LVPWd) thickness, diameters and cross-sectional area (CSA) of cardiac myocyte, as well as the ratio of heart weight to body weight (HW/BW), were markedly diminished in SHR + EA group, while the reduced left ventricular ejection fraction, left ventricular short axis fraction shortening, and E/A ratio were significantly ameliorated. The levels of Angiotensin-converting enzyme (ACE) and Angiotensin II Type 1 and 2 receptors (AT1R, AT2R) in SHRs were also significantly attenuated by EA. The results suggest that EA at bilateral PC6 could arrest the hypertension development and ameliorate the cardiac hypertrophy and malfunction in SHRs, which might be mediated by the regulation of ACE, AT1R, and AT2R. PMID:28293268

  11. Antihypertensive and Antihypertrophic Effects of Acupuncture at PC6 Acupoints in Spontaneously Hypertensive Rats and the Underlying Mechanisms.

    PubMed

    Xin, Juan-Juan; Gao, Jun-Hong; Wang, Yuan-Yuan; Lu, Feng-Yan; Zhao, Yu-Xue; Jing, Xiang-Hong; Yu, Xiao-Chun

    2017-01-01

    The aim of this work is to investigate the effect of electroacupuncture (EA) at PC6 on the hypertension and myocardial hypertrophy in spontaneously hypertensive rats (SHRs). Thirty SHRs were randomized into model, SHR + EA, and SHR + Sham EA group with WKY rats as normal control. EA was applied once a day in 8 consecutive weeks. The blood pressure (BP), cardiac function, and hypertrophy as well as the underlying mechanisms were investigated. After EA treatment, the enhanced BP in SHR + EA group was significantly lower compared to both the period before EA and model group. Echocardiographic, morphological studies showed that the enhanced left ventricular anterior and posterior wall end-diastolic (LVAWd and LVPWd) thickness, diameters and cross-sectional area (CSA) of cardiac myocyte, as well as the ratio of heart weight to body weight (HW/BW), were markedly diminished in SHR + EA group, while the reduced left ventricular ejection fraction, left ventricular short axis fraction shortening, and E/A ratio were significantly ameliorated. The levels of Angiotensin-converting enzyme (ACE) and Angiotensin II Type 1 and 2 receptors (AT1R, AT2R) in SHRs were also significantly attenuated by EA. The results suggest that EA at bilateral PC6 could arrest the hypertension development and ameliorate the cardiac hypertrophy and malfunction in SHRs, which might be mediated by the regulation of ACE, AT1R, and AT2R.

  12. 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

  13. Branched-chain amino acid-rich diet improves skeletal muscle wasting caused by cigarette smoke in rats.

    PubMed

    Tomoda, Koichi; Kubo, Kaoru; Hino, Kazuo; Kondoh, Yasunori; Nishii, Yasue; Koyama, Noriko; Yamamoto, Yoshifumi; Yoshikawa, Masanori; Kimura, Hiroshi

    2014-04-01

    Cigarette smoke induces skeletal muscle wasting by a mechanism not yet fully elucidated. Branched-chain amino acids (BCAA) in the skeletal muscles are useful energy sources during exercise or systemic stresses. We investigated the relationship between skeletal muscle wasting caused by cigarette smoke and changes in BCAA levels in the plasma and skeletal muscles of rats. Furthermore, the effects of BCAA-rich diet on muscle wasting caused by cigarette smoke were also investigated. Wistar Kyoto (WKY) rats that were fed with a control or a BCAA-rich diet were exposed to cigarette smoke for four weeks. After the exposure, the skeletal muscle weight and BCAA levels in plasma and the skeletal muscles were measured. Cigarette smoke significantly decreased the skeletal muscle weight and BCAA levels in both plasma and skeletal muscles, while a BCAA-rich diet increased the skeletal muscle weight and BCAA levels in both plasma and skeletal muscles that had decreased by cigarette smoke exposure. In conclusion, skeletal muscle wasting caused by cigarette smoke was related to the decrease of BCAA levels in the skeletal muscles, while a BCAA-rich diet may improve cases of cigarette smoke-induced skeletal muscle wasting.

  14. 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.

  15. Therapeutic effects of autologous bone marrow cells and metabolic intervention in the ischemic hindlimb of spontaneously hypertensive rats involve reduced cell senescence and CXCR4/Akt/eNOS pathways.

    PubMed

    de Nigris, Filomena; Balestrieri, Maria Luisa; Williams-Ignarro, Sharon; D'Armiento, Francesco P; Lerman, Lilach O; Byrns, Russell; Crimi, Ettore; Palagiano, Antonio; Fatigati, Gennaro; Ignarro, Louis J; Napoli, Claudio

    2007-10-01

    Peripheral arterial disease (PAD) is a major health problem, especially when associated with severe hypertension. Administration of autologous bone marrow cells (BMCs) is emerging as a novel intervention to induce neoangiogenesis in ischemic limb models and in patients with PAD. This study evaluates the neovascularization capacity of BMCs alone or in combination with metabolic cotreatment (0.8% vitamin E, 0.05% vitamin C, and 5% of L-arginine) in a rat model of ischemic hindlimbs of spontaneously hypertensive rats (SHR) and normotensive Wistar-Kyoto rats (WKY). Molecular mechanisms were investigated in bone marrow-derived endothelial progenitor cells (BM-EPC) derived from rats. BMC therapy increased blood flow and capillary densities and Ki67 proliferative marker, and it decreased interstitial fibrosis. These effects were amplified by metabolic cotreatment, an intervention that induces vascular protection at least partly through the nitric oxide (NO)/endothelial nitric oxide synthase (eNOS) pathway, reduction of systemic oxidative stress, and macrophage activation. In addition, BMC therapy alone and, more consistently, in combination with metabolic treatment, ameliorated BM-EPC functional activity via decreased cellular senescence and improved homing capacity by increasing CXCR4-expression levels. These data suggest potential therapeutic effects of autologous BMCs and metabolic treatment in hypertensive PAD patients.

  16. Whisker Deprivation Drives Two Phases of Inhibitory Synapse Weakening in Layer 4 of Rat Somatosensory Cortex.

    PubMed

    Gainey, Melanie A; Wolfe, Renna; Pourzia, Olivia; Feldman, Daniel E

    2016-01-01

    Inhibitory synapse development in sensory neocortex is experience-dependent, with sustained sensory deprivation yielding fewer and weaker inhibitory synapses. Whether this represents arrest of synapse maturation, or a more complex set of processes, is unclear. To test this, we measured the dynamics of inhibitory synapse development in layer 4 of rat somatosensory cortex (S1) during continuous whisker deprivation from postnatal day 7, and in age-matched controls. In deprived columns, spontaneous miniature inhibitory postsynaptic currents (mIPSCs) and evoked IPSCs developed normally until P15, when IPSC amplitude transiently decreased, recovering by P16 despite ongoing deprivation. IPSCs remained normal until P22, when a second, sustained phase of weakening began. Delaying deprivation onset by 5 days prevented the P15 weakening. Both early and late phase weakening involved measurable reduction in IPSC amplitude relative to prior time points. Thus, deprivation appears to drive two distinct phases of active IPSC weakening, rather than simple arrest of synapse maturation.

  17. Absorption and metabolism of ( sup 3 H)arachidonic and ( sup 14 C)linoleic acid in essential fatty acid-deficient rats

    SciTech Connect

    Hjelte, L.; Melin, T.; Nilsson, A.; Strandvik, B. )

    1990-07-01

    ({sup 3}H)arachidonic acid (20:4) and ({sup 14}C)linoleic acid (18:2) were fed in a triolein emulsion to essential fatty acid-deficient (EFAD) rats and to age-matched controls. Tissues were analyzed for radioactivity of different lipid classes after 1, 2, and 4 h. As in earlier studies, control rats retained more ({sup 3}H)20:4 than ({sup 14}C)18:2 in all organs except adipose tissue. In EFAD rats, recovery of ({sup 14}C)18:2 was increased in small intestine, liver, heart, and kidneys. In comparison to controls, EFAD rats retained much more ({sup 14}C)18:2 in phospholipids of these organs. The increase in the incorporation of both {sup 3}H and {sup 14}C into phosphatidylethanolamine was particularly pronounced. Another striking feature was the drastic increase in the retention after 4 h of {sup 14}C in cardiolipin, which is specifically located in the inner mitochondrial membrane. In contrast, incorporation of both {sup 3}H and {sup 14}C into phosphatidylinositol was decreased or unchanged in EFAD rats. Although fecal fat excretion was increased there was no evidence for a malabsorption or an increased retention in intestinal triacyglycerol of the radioactive fatty acids in EFAD rats. The proportion of ({sup 14}C)18:2 that had been converted to ({sup 14}C)20:4 was generally low but increased significantly with time in the liver and intestine of EFAD rats.

  18. Beer promotes high levels of alcohol intake in adolescent and adult alcohol-preferring rats.

    PubMed

    Hargreaves, Garth A; Wang, Emyo Y J; Lawrence, Andrew J; McGregor, Iain S

    2011-08-01

    Previous studies suggest that high levels of alcohol consumption can be obtained in laboratory rats by using beer as a test solution. The present study extended these observations to examine the intake of beer and equivalent dilute ethanol solutions with an inbred line of alcohol-preferring P rats. In Experiment 1, male adolescent P rats and age-matched Wistar rats had access to either beer or equivalent ethanol solutions for 1h daily in a custom-built lickometer apparatus. In subsequent experiments, adolescent (Experiment 2) and adult (Experiment 3) male P rats were given continuous 24-h home cage access to beer or dilute ethanol solutions, with concomitant access to lab chow and water. In each experiment, the alcohol content of the beer and dilute ethanol solutions was gradually increased from 0.4, 1.4, 2.4, 3.4, 4.4, 5 to 10% EtOH (vol/vol). All three experiments showed a major augmentation of alcohol intake when rats were given beer compared with equivalent ethanol solutions. In Experiment 1, the overall intake of beer was higher in P rats compared with Wistar rats, but no strain difference was found during the 1-h sessions with plain ethanol consumption. Experiment 1 also showed that an alcohol deprivation effect was more readily obtained in rats with a history of consuming beer rather than plain ethanol solutions. In Experiments 2 and 3, voluntary beer intake in P rats represented ethanol intake of 10-15 g/kg/day, among the highest reported in any study with rats. This excessive consumption was most apparent in adolescent rats. Beer consumption markedly exceeded plain ethanol intake in these experiments except at the highest alcohol concentration (10%) tested. The advantage of using beer rather than dilute ethanol solutions in both selected and nonselected rat strains is therefore confirmed. Our findings encourage the use of beer with alcohol-preferring rats in future research that seeks to obtain high levels of alcohol self-administration.

  19. Layer-specific blood-flow MRI of retinitis pigmentosa in RCS rats.

    PubMed

    Li, Guang; De La Garza, Bryan; Shih, Yen-Yu I; Muir, Eric R; Duong, Timothy Q

    2012-08-01

    The Royal College of Surgeons (RCS) rat is an established animal model of retinitis pigmentosa, a family of inherited retinal diseases which starts with loss of peripheral vision and progresses to eventual blindness. Blood flow (BF), an important physiological parameter, is intricately coupled to metabolic function under normal physiological conditions and is perturbed in many neurological and retinal diseases. This study reports non-invasive high-resolution MRI (44 × 44 × 600 μm) to image quantitative retinal and choroidal BF and layer-specific retinal thicknesses in RCS rat retinas at different stages of retinal degeneration compared with age-matched controls. The unique ability to separate retinal and choroidal BF was made possible by the depth-resolved MRI technique. RBF decreased with progressive retinal degeneration, but ChBF did not change in RCS rats up to post-natal day 90. We concluded that choroidal and retinal circulations have different susceptibility to progressive retinal degeneration in RCS rats. Layer-specific retinal thickness became progressively thinner and was corroborated by histological analysis in the same animals. MRI can detect progressive anatomical and BF changes during retinal degeneration with laminar resolution.

  20. 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.

  1. 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.

  2. Segmental Aging Underlies the Development of a Parkinson Phenotype in the AS/AGU Rat

    PubMed Central

    Khojah, Sohair M.; Payne, Anthony P.; McGuinness, Dagmara; Shiels, Paul G.

    2016-01-01

    There is a paucity of information on the molecular biology of aging processes in the brain. We have used biomarkers of aging (SA β-Gal, p16Ink4a, Sirt5, Sirt6, and Sirt7) to demonstrate the presence of an accelerated aging phenotype across different brain regions in the AS/AGU rat, a spontaneous Parkinsonian mutant of PKCγ derived from a parental AS strain. P16INK4a expression was significantly higher in AS/AGU animals compared to age-matched AS controls (p < 0.001) and displayed segmental expression across various brain regions. The age-related expression of sirtuins similarly showed differences between strains and between brain regions. Our data clearly show segmental aging processes within the rat brain, and that these are accelerated in the AS/AGU mutant. The accelerated aging, Parkinsonian phenotype, and disruption to dopamine signalling in the basal ganglia in AS/AGU rats, suggests that this rat strain represents a useful model for studies of development and progression of Parkinson’s disease in the context of biological aging and may offer unique mechanistic insights into the biology of aging. PMID:27763519

  3. Kynurenic acid, an aryl hydrocarbon receptor ligand, is elevated in serum of Zucker fatty rats

    PubMed Central

    Oxenkrug, G; Cornicelli, J; van der Hart, M; Roeser, J; Summergrad, P

    2016-01-01

    Obesity is an increasingly urgent global problem and the molecular mechanisms of obesity are not fully understood. Dysregulation of the tryptophan (Trp) – kynurenine (Kyn) metabolic pathway (TKP) have been suggested as a mechanism of obesity and described in obese humans and in animal models of obesity. However, to the best of our knowledge, TKP metabolism has not been studied in leptin-receptor-deficient Zucker fatty rats (ZFR) (fa/fa), the best-known and most widely used rat model of obesity. We were interested to determine if there are any deviations of TKP in ZFR. Concentrations of major TKP metabolites were evaluated (HPLC- MS method) in serum of ZFR (fa/fa) and age-matched lean rats (FA/-). Concentrations of kynurenic acid (KYNA) were 50% higher in ZFR than in lean rats (p<0.004, Mann-Whitney two-tailed test). Anthranilic acid (AA) concentrations, while elevated by 33%, did not reach statistical significance (p<0.04, one-tailed test). Elevated KYNA serum concentrations might contribute to development of obesity via KYNA-induced activation of aryl hydrocarbon receptor. Present results warrant further studies of KYNA and AA in ZFR and other animal models of obesity. PMID:27738521

  4. Effect of exercise training on ethanol-induced oxidative damage in aged rats.

    PubMed

    Mallikarjuna, K; Nishanth, K; Hou, Chien-Wen; Kuo, Chia-Hua; Sathyavelu Reddy, K

    2009-02-01

    It is well known that lipid peroxidation increases with age, and alcohol drinking further exacerbates this damage. The present study determined the effect of regular exercise training on alcohol-induced oxidative damage and antioxidant status in the liver of aged animals. The age-matched Wistar albino rats (3 months young, n=24; 18 months old, n=24) were evenly divided into four groups: control (C), exercise trained (Ex), ethanol drinking (Et), and exercise plus ethanol drinking (Ex+Et). With ethanol drinking, hepatic malondialdehyde (MDA) level was significantly elevated above control (P<.001), whereas glutathione (GSH) and ascorbic acid (vitamin C) contents were significantly decreased below control. These changes were found to be greater in the aged rats than those of the young rats. For both age groups, exercise training significantly reversed the increase in MDA and decreases in GSH and ascorbic acid induced by ethanol drinking. The present study showed that ethanol-induced deterioration in lipid peroxidation and reduction in antioxidant status in the liver were exacerbated with age. Here, we found that exercise training significantly reversed the adverse conditions that were caused by ethanol in aged rats.

  5. 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.

  6. 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.

  7. 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.

  8. Systemic elevation of interleukin-15 in vivo promotes apoptosis in skeletal muscles of young adult and aged rats.

    PubMed

    Pistilli, Emidio E; Alway, Stephen E

    2008-08-15

    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.

  9. Evaluation of amygdaloid neuronal dendritic arborization enhancing effect of Centella asiatica (Linn) fresh leaf extract in adult rats.

    PubMed

    Mohandas Rao, K G; Rao, Muddanna S; Rao, Gurumadhva S

    2012-12-03

    OBJECTIVE: Centella asiatica (CeA), a creeper, growing in moist places in India and other Asian countries. Leaves of CeA are used for memory enhancement in Ayurvedic system of medicine, an alternative system of medicine originated from India. In the present study, we have investigated the role of CeA fresh leaf extract treatment on adult rats on dendritic morphology of amygdaloid neurons, one of the regions concerned with learning and memory. METHODS: Adult rats (2.5-month old) were fed with 2, 4 and 6 mL/(day kg) of fresh leaf extract of CeA for 2, 4 and 6 weeks. After the treatment period the rats were killed, brains were removed and amygdaloid neurons were impregnated with silver nitrate (Golgi staining). Such silver impregnated amygdaloid neurons were traced using camera lucida and dendritic branching points (a measure of dendritic arborization) and intersections (a measure of dendritic length) were quantified. These data were compared with those of age matched control rats. RESULTS: The results showed a significant increase in the dendritic length (intersections) and dendritic branching points in amygdaloid neurons of the rats treated with higher dose [6 mL/(day·kg)] of CeA for longer period of time (i.e. 6 weeks). CONCLUSIONS: Constituents/active principles present CeA fresh leaf extract has neuronal dendritic growth stimulating property; hence it can be used for enhancing neuronal dendrites in stress and other neurodegenerative and memory disorders.

  10. Type 2 diabetes alters bone and marrow blood flow and vascular control mechanisms in the ZDF rat.

    PubMed

    Stabley, John N; Prisby, Rhonda D; Behnke, Bradley J; Delp, Michael D

    2015-04-01

    Bone health and cardiovascular function are compromised in individuals with type 2 diabetes mellitus (T2DM). The purpose of this study was to determine whether skeletal vascular control mechanisms are altered during the progression of T2DM in Zucker diabetic fatty (ZDF) rats. 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 potassium chloride, norepinephrine (NE), and a myogenic vasoconstrictor were determined in vitro. Few changes in the PNA vasomotor responses occurred for the prediabetic and short-term diabetic conditions. Endothelium-dependent and -independent vasodilation were reduced, and NE and myogenic vasoconstriction were increased 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 N(G)-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 indicate that the profound impairment of the bone circulation may contribute to the osteopenia found to occur in long bones during chronic T2DM.

  11. Abnormal cardiac function in the streptozotocin-diabetic rat. Changes in active and passive properties of the left ventricle.

    PubMed Central

    Litwin, S E; Raya, T E; Anderson, P G; Daugherty, S; Goldman, S

    1990-01-01

    To provide an integrated assessment of changes in systolic and diastolic function in diabetic rats, we measured conscious hemodynamics and performed ex vivo analysis of left ventricular passive-elastic properties. Rats given streptozotocin (STZ) 65 mg/kg i.v. (n = 14) were compared with untreated age-matched controls (n = 15) and rats treated with insulin after administration of STZ (n = 11). After 7 d, diabetic rats exhibited decreases in heart rate and peak developed left ventricular (LV) pressure during aortic occlusion. After 26 d of diabetes there were significant decreases in resting LV systolic pressure, developed pressure, and maximal +dP/dt, whereas LV end-diastolic pressure increased and the time constant of LV relaxation was prolonged. The passive LV pressure-volume relationship was progressively shifted away from the pressure axis, and the overall chamber stiffness constant was decreased. However, "operating chamber stiffness" calculated at end-diastolic pressure was increased at 7 d, and unchanged at 26 d. LV cavity/wall volume and end-diastolic volume were increased after 26 d of diabetes. Myocardial stiffness was unchanged at both time intervals. All of the above abnormalities were reversed by the administration of insulin. We conclude that the hemodynamic and passive-elastic changes that occur in diabetic rats represent an early dilated cardiomyopathy which is reversible with insulin. Images PMID:2200804

  12. Prior Parity Positively Regulates Learning and Memory in Young and Middle-Aged Rats

    PubMed Central

    Zimberknopf, Erica; Xavier, Gilberto F; Kinsley, Craig H; Felicio, Luciano F

    2011-01-01

    Reproductive experience in female rats modifies acquired behaviors, induces long-lasting functional neuroadaptations and can also modify spatial learning and memory. The present study supports and expands this knowledge base by employing the Morris water maze, which measures spatial memory. Age-matched young adult (YNG) nulliparous (NULL; nonmated) and primiparous (PRIM; one pregnancy and lactation) female rats were tested 15 d after the litter's weaning. In addition, corresponding middle-aged (AGD) PRIM (mated in young adulthood so that pregnancy, parturition, and lactation occurred at the same age as in YNG PRIM) and NULL female rats were tested at 18 mo of age. Behavioral evaluation included: 1) acquisition of reference memory (platform location was fixed for 14 to 19 d of testing); 2) retrieval of this information associated with extinction of the acquired response (probe test involving removal of the platform 24 h after the last training session); and 3) performance in a working memory version of the task (platform presented in a novel location every day for 13 d, and maintained in a fixed location within each day). YNG PRIM outperformed N