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Sample records for attenuates salt-sensitive hypertension

  1. CXCL16 Deficiency Attenuates Renal Injury and Fibrosis in Salt-Sensitive Hypertension

    PubMed Central

    Liang, Hua; Ma, Zhiheng; Peng, Hui; He, Liqun; Hu, Zhaoyong; Wang, Yanlin

    2016-01-01

    Inflammation plays an important role in the pathogenesis of hypertensive kidney disease. However, the molecular mechanisms underlying the induction of inflammation are not completely understood. We have found that CXCL16 is induced in the kidney in deoxycorticosterone acetate (DOCA)-salt hypertension. Here we examined whether CXCL16 is involved in DOCA-salt-induced renal inflammation and fibrosis. Wild-type and CXCL16 knockout mice were subjected to uninephrectomy and DOCA-salt treatment for 3 weeks. There was no difference in blood pressure at baseline between wild-type and CXCL16 knockout mice. DOCA-salt treatment resulted in significant elevation in blood pressure that was comparable between wild-type and CXCL16 knockout mice. CXCL16 knockout mice exhibited less severe renal dysfunction, proteinuria, and fibrosis after DOCA-salt treatment compared with wild-type mice. CXCL16 deficiency attenuated extracellular matrix protein production and suppressed bone marrow–derived fibroblast accumulation and myofibroblast formation in the kidneys following DOCA-salt treatment. Furthermore, CXCL16 deficiency reduced macrophage and T cell infiltration into the kidneys in response to DOCA-salt hypertension. Taken together, our results indicate that CXCL16 plays a key role in the pathogenesis of renal injury and fibrosis in salt-sensitive hypertension through regulation of bone marrow–derived fibroblast accumulation and macrophage and T cell infiltration. PMID:27353044

  2. Inhibition of MMP-9 attenuates hypertensive cerebrovascular dysfunction in Dahl salt-sensitive rats.

    PubMed

    Kalani, Anuradha; Pushpakumar, Sathnur B; Vacek, Jonathan C; Tyagi, Suresh C; Tyagi, Neetu

    2016-02-01

    Hypertensive cerebropathy is a pathological condition associated with cerebral edema and disruption of the blood-brain barrier. However, the molecular pathways leading to this condition remains obscure. We hypothesize that MMP-9 inhibition can help reducing blood pressure and endothelial disruption associated with hypertensive cerebropathy. Dahl salt-sensitive (Dahl/SS) and Lewis rats were fed with high-salt diet for 6 weeks and then treated without and with GM6001 (MMP inhibitor). Treatment of GM6001 (1.2 mg/kg body weight) was administered through intraperitoneal injections on alternate days for 4 weeks. GM6001 non-administered groups were given vehicle (0.9% NaCl in water) treatment as control. Blood pressure was measured by tail-cuff method. The brain tissues were analyzed for oxidative/nitrosative stress, vascular MMP-9 expression, and tight junction proteins (TJPs). GM6001 treatment significantly reduced mean blood pressure in Dahl/SS rats which was significantly higher in vehicle-treated Dahl/SS rats. MMP-9 expression and activity was also considerably reduced in GM6001-treated Dahl/SS rats, which was otherwise notably increased in vehicle-treated Dahl/SS rats. Similarly MMP-9 expression in cerebral vessels of GM6001-treated Dahl/SS rats was also alleviated, as devised by immunohistochemistry analysis. Oxidative/nitrosative stress was significantly higher in vehicle-treated Dahl/SS rats as determined by biochemical estimations of malondialdehyde, nitrite, reactive oxygen species, and glutathione levels. RT-PCR and immunohistochemistry analysis further confirmed considerable alterations of TJPs in hypertensive rats. Interestingly, GM6001 treatment significantly ameliorated oxidative/nitrosative stress and TJPs, which suggest restoration of vascular integrity in Dahl/SS rats. These findings determined that pharmacological inhibition of MMP-9 in hypertensive Dahl-SS rats attenuate high blood pressure and hypertension-associated cerebrovascular pathology. PMID

  3. Interleukin-6 inhibition attenuates hypertension and associated renal damage in Dahl salt-sensitive rats.

    PubMed

    Hashmat, Shireen; Rudemiller, Nathan; Lund, Hayley; Abais-Battad, Justine M; Van Why, Scott; Mattson, David L

    2016-09-01

    Immune cells in the kidney are implicated in the development of hypertension and renal damage in the Dahl salt-sensitive (SS) rat. Interestingly, interleukin 6 (IL-6) mRNA is 54-fold higher in T-lymphocytes isolated from the kidney compared with circulating T-lymphocytes. The present experiments assessed the role of IL-6 in the development of SS hypertension by treating rats (n = 13-14/group) with an IL-6 neutralizing antibody or normal IgG during an 11-day period of high-salt (4.0% NaCl chow) intake. The mean arterial pressure (MAP) and urine albumin excretion rates (Ualb) were not different between the groups fed low salt (0.4% NaCl). Following 11 days of drug treatment and high salt, however, the rats receiving anti-IL-6 demonstrated a 47% reduction of IL-6 in the renal medulla compared with control SS. Moreover, the increase in MAP following 11 days of high-NaCl intake was significantly attenuated in SS administered anti-IL-6 compared with the control group (138 ± 3 vs. 149 ± 3 mmHg) as was the salt-induced increase in Ualb and glomerular and tubular damage. To investigate potential mechanisms of action, a flow cytometric analysis of immune cells in the kidney (n = 8-9/group) demonstrated that the total number of monocytes and macrophages was significantly lower in the treatment vs. the control group. The total number of T- and B-lymphocytes in the kidneys was not different between groups. These studies indicate that IL-6 production may participate in the development of SS hypertension and end-organ damage by mediating increased infiltration or proliferation of macrophages into the kidney. PMID:27279492

  4. High dietary cholecalciferol increases plasma 25-hydroxycholecalciferol concentration, but does not attenuate the hypertension of Dahl salt-sensitive rats fed a high salt diet

    PubMed Central

    Thierry-Palmer, Myrtle; Cephas, Stacy; Muttardy, Farah F.; Al-Mahmoud, Ahmad

    2008-01-01

    The Dahl salt-sensitive rat, a model for salt-induced hypertension, develops hypovitaminosis D during high salt intake, which is caused by loss of protein-bound vitamin D metabolites into urine. We tested the hypothesis that high dietary cholecalciferol (5- and 10-fold standard) would increase plasma 25-hydroxycholecalciferol (25-OHD3) concentration (indicator of vitamin D status) of salt-sensitive rats during high salt intake. Salt-sensitive rats were fed 0.3% salt (low salt, LS), 3% salt (high salt, HS), 3% salt and 7.5 μg cholecalciferol/d (HS-D5), or 3% salt and 15 μg cholecalciferol/d (HS-D10) and sacrificed at week 4. Plasma 25-OHD3 concentrations of the two groups of HS-D rats were similar to that of LS rats and more than twice that of HS rats. Urinary cholecalciferol metabolite content of HS-D rats was more than seven times that of HS rats. Systolic blood pressures of the hypertensive HS and HS-D rats did not significantly differ, whereas LS rats were not hypertensive. We conclude that high dietary cholecalciferol increases plasma 25-OHD3 concentration, but does not attenuate the hypertension of salt-sensitive rats during high salt intake. Low salt intake may be necessary to both maintain optimal vitamin D status and prevent hypertension in salt-sensitive individuals. PMID:18554900

  5. Mechanisms of Salt-Sensitive Hypertension.

    PubMed

    Luzardo, Leonella; Noboa, Oscar; Boggia, José

    2015-01-01

    Hypertension and its consequences, including heart failure, stroke, and kidney disease, are responsible for substantial morbidity and mortality worldwide. Lifestyle changes, particularly sodium reduction, contribute to blood pressure control. However, not all individuals, whether normotensive or hypertensive, have the same susceptibility to the effects of salt. While a variety of approaches have been proposed to identify salt sensitive patients, there is no consensus for a definition of salt sensitivity and the precise mechanisms that explain their association are not yet fully understood. In this review we summarize the current understanding of the various pathophysiological mechanisms potentially involved in determining the salt sensitive phenotype. Genetic, neuronal, and immune alterations are reviewed. Additionally, we provide an update on the current knowledge of a new approach proposing the interstitium of the skin may act as a sodium reservoir. The role of dietary potassium on salt sensitive hypertension is also summarized. PMID:26028243

  6. Mutation of SH2B3 (LNK), a genome-wide association study candidate for hypertension, attenuates Dahl salt-sensitive hypertension via inflammatory modulation.

    PubMed

    Rudemiller, Nathan P; Lund, Hayley; Priestley, Jessica R C; Endres, Bradley T; Prokop, Jeremy W; Jacob, Howard J; Geurts, Aron M; Cohen, Eric P; Mattson, David L

    2015-05-01

    Human genome-wide association studies have linked SH2B adaptor protein 3 (SH2B3, LNK) to hypertension and renal disease, although little experimental investigation has been performed to verify a role for SH2B3 in these pathologies. SH2B3, a member of the SH2B adaptor protein family, is an intracellular adaptor protein that functions as a negative regulator in many signaling pathways, including inflammatory signaling processes. To explore a mechanistic link between SH2B3 and hypertension, we targeted the SH2B3 gene for mutation on the Dahl salt-sensitive (SS) rat genetic background with zinc-finger nucleases. The resulting mutation was a 6-bp, in-frame deletion within a highly conserved region of the Src homology 2 (SH2) domain of SH2B3. This mutation significantly attenuated Dahl SS hypertension and renal disease. Also, infiltration of leukocytes into the kidneys, a key mediator of Dahl SS pathology, was significantly blunted in the Sh2b3(em1Mcwi) mutant rats. To determine whether this was because of differences in immune signaling, bone marrow transplant studies were performed in which Dahl SS and Sh2b3(em1Mcwi) mutants underwent total body irradiation and were then transplanted with Dahl SS or Sh2b3(em1Mcwi) mutant bone marrow. Rats that received Sh2b3(em1Mcwi) mutant bone marrow had a significant reduction in mean arterial pressure and kidney injury when placed on a high salt diet (4% NaCl). These data further support a role for the immune system as a modulator of disease severity in the pathogenesis of hypertension and provide insight into inflammatory mechanisms at play in human hypertension and renal disease. PMID:25776069

  7. Mutation within the hinge region of the transcription factor Nr2f2 attenuates salt-sensitive hypertension

    PubMed Central

    Kumarasamy, Sivarajan; Waghulde, Harshal; Gopalakrishnan, Kathirvel; Mell, Blair; Morgan, Eric; Joe, Bina

    2015-01-01

    Genome-wide association studies (GWAS) have prioritized a transcription factor, Nuclear Receptor 2 Family 2 (NR2F2), as being associated with essential hypertension in humans. Here we provide evidence that validates this association and indicates that Nr2f2 is a genetic determinant of blood pressure (BP). Using the zinc-finger nuclease technology, the generation of a targeted Nr2f2-edited rat model is reported. The resulting gene-edited rats have a 15bp deletion in exon 2 leading to a 5 amino acid deletion in the hinge region of the mutant Nr2f2 protein. Both systolic and diastolic blood pressures of the Nr2f2mutant rats are significantly lower than controls. Because the hinge region of Nr2f2 is required for interaction with Friend of Gata2 (Fog2), protein-protein interaction is examined. Interaction of Nr2f2mutant protein with Fog2 is greater than that with the wild type Nr2f2 indicating that the extent of interaction between these two transcription factors critically influences BP. PMID:25687237

  8. Diagnostic tools for hypertension and salt sensitivity testing

    PubMed Central

    Felder, Robin A.; White, Marquitta J.; Williams, Scott M.; Jose, Pedro A.

    2013-01-01

    Purpose of review One-third of the world’s population has hypertension and it is responsible for almost 50% of deaths from stroke or coronary heart disease. These statistics do not distinguish salt-sensitive from salt-resistant hypertension or include normotensives who are salt-sensitive even though salt sensitivity, independent of blood pressure, is a risk factor for cardiovascular and other diseases, including cancer. This review describes new personalized diagnostic tools for salt sensitivity. Recent findings The relationship between salt intake and cardiovascular risk is not linear, but rather fits a J-shaped curve relationship. Thus, a low-salt diet may not be beneficial to everyone and may paradoxically increase blood pressure in some individuals. Current surrogate markers of salt sensitivity are not adequately sensitive or specific. Tests in the urine that could be surrogate markers of salt sensitivity with a quick turn-around time include renal proximal tubule cells, exosomes, and microRNA shed in the urine. Summary Accurate testing of salt sensitivity is not only laborious but also expensive, and with low patient compliance. Patients who have normal blood pressure but are salt-sensitive cannot be diagnosed in an office setting and there are no laboratory tests for salt sensitivity. Urinary surrogate markers for salt sensitivity are being developed. PMID:23197156

  9. Salt Sensitivity: Challenging and Controversial Phenotype of Primary Hypertension.

    PubMed

    Iatrino, Rossella; Manunta, Paolo; Zagato, Laura

    2016-09-01

    Increases in life expectancy and cardiovascular adverse events in patients with hypertension highlight the need for new risk-reduction strategies to reduce the burden of degenerative diseases. Among the environmental factors, high salt consumption is currently considered the most important risk factor of hypertension. However, while high salt intake significantly raises blood pressure in some individuals, others do not show variation or even decrease their blood pressure. This heterogeneity is respectively classified as salt sensitivity and salt resistance. In this review, we propose salt sensitivity as a useful phenotype to unravel the mechanistic complexity of primary hypertension. The individual variability in blood pressure modification in response to salt intake changes derives from the combination of genetic and environmental determinants. This combination of random and non random determinants leads to the development of a personal index of sensitivity to salt. However, those genes involved in susceptibility to salt are still not completely identified, and the triggering mechanisms underlying the following development of hypertension still remain uncovered. One reason might be represented by the absence of a specific protocol, universally followed, for a standard definition of salt sensitivity. Another reason may be linked to the absence of common criteria for patient recruitment during clinical studies. Thus, the generation of a reliable approach for a proper recognition of this personal index of sensitivity to salt, and through it the identification of novel therapeutic targets for primary hypertension, should be one of the aspirations for the scientific community. PMID:27614755

  10. Caffeine intake antagonizes salt sensitive hypertension through improvement of renal sodium handling

    PubMed Central

    Yu, Hao; Yang, Tao; Gao, Peng; Wei, Xing; Zhang, Hexuan; Xiong, Shiqiang; Lu, Zongshi; Li, Li; Wei, Xiao; Chen, Jing; Zhao, Yu; Arendshorst, William J.; Shang, Qianhui; Liu, Daoyan; Zhu, Zhiming

    2016-01-01

    High salt intake is a major risk factor for hypertension. Although acute caffeine intake produces moderate diuresis and natriuresis, caffeine increases the blood pressure (BP) through activating sympathetic activity. However, the long-term effects of caffeine on urinary sodium excretion and blood pressure are rarely investigated. Here, we investigated whether chronic caffeine administration antagonizes salt sensitive hypertension by promoting urinary sodium excretion. Dahl salt-sensitive (Dahl-S) rats were fed with high salt diet with or without 0.1% caffeine in drinking water for 15 days. The BP, heart rate and locomotor activity of rats was analyzed and urinary sodium excretion was determined. The renal epithelial Na+ channel (ENaC) expression and function were measured by in vivo and in vitro experiments. Chronic consumption of caffeine attenuates hypertension induced by high salt without affecting sympathetic nerve activity in Dahl-S rats. The renal α-ENaC expression and ENaC activity of rats decreased after chronic caffeine administration. Caffeine increased phosphorylation of AMPK and decrease α-ENaC expression in cortical collecting duct cells. Inhibiting AMPK abolished the effect of caffeine on α-ENaC. Chronic caffeine intake prevented the development of salt-sensitive hypertension through promoting urinary sodium excretion, which was associated with activation of renal AMPK and inhibition of renal tubular ENaC. PMID:27173481

  11. Caffeine intake antagonizes salt sensitive hypertension through improvement of renal sodium handling.

    PubMed

    Yu, Hao; Yang, Tao; Gao, Peng; Wei, Xing; Zhang, Hexuan; Xiong, Shiqiang; Lu, Zongshi; Li, Li; Wei, Xiao; Chen, Jing; Zhao, Yu; Arendshorst, William J; Shang, Qianhui; Liu, Daoyan; Zhu, Zhiming

    2016-01-01

    High salt intake is a major risk factor for hypertension. Although acute caffeine intake produces moderate diuresis and natriuresis, caffeine increases the blood pressure (BP) through activating sympathetic activity. However, the long-term effects of caffeine on urinary sodium excretion and blood pressure are rarely investigated. Here, we investigated whether chronic caffeine administration antagonizes salt sensitive hypertension by promoting urinary sodium excretion. Dahl salt-sensitive (Dahl-S) rats were fed with high salt diet with or without 0.1% caffeine in drinking water for 15 days. The BP, heart rate and locomotor activity of rats was analyzed and urinary sodium excretion was determined. The renal epithelial Na(+) channel (ENaC) expression and function were measured by in vivo and in vitro experiments. Chronic consumption of caffeine attenuates hypertension induced by high salt without affecting sympathetic nerve activity in Dahl-S rats. The renal α-ENaC expression and ENaC activity of rats decreased after chronic caffeine administration. Caffeine increased phosphorylation of AMPK and decrease α-ENaC expression in cortical collecting duct cells. Inhibiting AMPK abolished the effect of caffeine on α-ENaC. Chronic caffeine intake prevented the development of salt-sensitive hypertension through promoting urinary sodium excretion, which was associated with activation of renal AMPK and inhibition of renal tubular ENaC. PMID:27173481

  12. Renal Tumor Necrosis Factor α Contributes to Hypertension in Dahl Salt-Sensitive Rats

    PubMed Central

    Huang, Baorui; Cheng, Yuan; Usa, Kristie; Liu, Yong; Baker, Maria Angeles; Mattson, David L.; He, Yongcheng; Wang, Niansong; Liang, Mingyu

    2016-01-01

    Tumor necrosis factor α (TNFα) is a major proinflammatory cytokine and its level is elevated in hypertensive states. Inflammation occurs in the kidneys during the development of hypertension. We hypothesized that TNFα specifically in the kidney contributes to the development of hypertension and renal injury in Dahl salt-sensitive (SS) rats, a widely used model of human salt-sensitive hypertension and renal injury. SS rats were chronically instrumented for renal interstitial infusion and blood pressure measurement in conscious, freely moving state. Gene expression was measured using real-time PCR and renal injury assessed with histological analysis. The abundance of TNFα in the renal medulla of SS rats, but not the salt-insensitive congenic SS.13BN26 rats, was significantly increased when rats had been fed a high-salt diet for 7 days (n = 6 or 9, p < 0.01). The abundance of TNFα receptors in the renal medulla was significantly higher in SS rats than SS.13BN26 rats. Renal interstitial administration of Etanercept, an inhibitor of TNFα, significantly attenuated the development of hypertension in SS rats on a high-salt diet (n = 7–8, p < 0.05). Glomerulosclerosis and interstitial fibrosis were also significantly ameliorated. These findings indicate intrarenal TNFα contributes to the development of hypertension and renal injury in SS rats. PMID:26916681

  13. Renal Tumor Necrosis Factor α Contributes to Hypertension in Dahl Salt-Sensitive Rats.

    PubMed

    Huang, Baorui; Cheng, Yuan; Usa, Kristie; Liu, Yong; Baker, Maria Angeles; Mattson, David L; He, Yongcheng; Wang, Niansong; Liang, Mingyu

    2016-01-01

    Tumor necrosis factor α (TNFα) is a major proinflammatory cytokine and its level is elevated in hypertensive states. Inflammation occurs in the kidneys during the development of hypertension. We hypothesized that TNFα specifically in the kidney contributes to the development of hypertension and renal injury in Dahl salt-sensitive (SS) rats, a widely used model of human salt-sensitive hypertension and renal injury. SS rats were chronically instrumented for renal interstitial infusion and blood pressure measurement in conscious, freely moving state. Gene expression was measured using real-time PCR and renal injury assessed with histological analysis. The abundance of TNFα in the renal medulla of SS rats, but not the salt-insensitive congenic SS.13(BN26) rats, was significantly increased when rats had been fed a high-salt diet for 7 days (n = 6 or 9, p < 0.01). The abundance of TNFα receptors in the renal medulla was significantly higher in SS rats than SS.13(BN26) rats. Renal interstitial administration of Etanercept, an inhibitor of TNFα, significantly attenuated the development of hypertension in SS rats on a high-salt diet (n = 7-8, p < 0.05). Glomerulosclerosis and interstitial fibrosis were also significantly ameliorated. These findings indicate intrarenal TNFα contributes to the development of hypertension and renal injury in SS rats. PMID:26916681

  14. GPER activation ameliorates aortic remodeling induced by salt-sensitive hypertension.

    PubMed

    Liu, Liu; Kashyap, Shreya; Murphy, Brennah; Hutson, Dillion D; Budish, Rebecca A; Trimmer, Emma H; Zimmerman, Margaret A; Trask, Aaron J; Miller, Kristin S; Chappell, Mark C; Lindsey, Sarah H

    2016-04-15

    The mRen2 female rat is an estrogen- and salt-sensitive model of hypertension that reflects the higher pressure and salt sensitivity associated with menopause. We previously showed that the G protein-coupled estrogen receptor (GPER) mediates estrogenic effects in this model. The current study hypothesized that GPER protects against vascular injury during salt loading. Intact mRen2 female rats were fed a normal (NS; 0.5% Na(+)) or high-salt diet (HS; 4% Na(+)) for 10 wk, which significantly increased systolic blood pressure (149 ± 5 vs. 224 ± 8 mmHg;P< 0.001). Treatment with the selective GPER agonist G-1 for 2 wk did not alter salt-sensitive hypertension (216 ± 4 mmHg;P> 0.05) or ex vivo vascular responses to angiotensin II or phenylephrine (P> 0.05). However, G-1 significantly attenuated salt-induced aortic remodeling assessed by media-to-lumen ratio (NS: 0.43; HS+veh: 0.89; HS+G-1: 0.61;P< 0.05). Aortic thickening was not accompanied by changes in collagen, elastin, or medial proliferation. However, HS induced increases in medial layer glycosaminoglycans (0.07 vs. 0.42 mm(2);P< 0.001) and lipid peroxidation (0.11 vs. 0.51 mm(2);P< 0.01), both of which were reduced by G-1 (0.20 mm(2)and 0.23 mm(2); both P< 0.05). We conclude that GPER's beneficial actions in the aorta of salt-loaded mRen2 females occur independently of changes in blood pressure and vasoreactivity. GPER-induced attenuation of aortic remodeling was associated with a reduction in oxidative stress and decreased accumulation of glycosaminoglycans. Endogenous activation of GPER may protect females from salt- and pressure-induced vascular damage. PMID:26873963

  15. Chronic Antagonism of the Mineralocorticoid Receptor Ameliorates Hypertension and End Organ Damage in a Rodent Model of Salt-Sensitive Hypertension

    PubMed Central

    Zhou, Xiaoyan; Crook, Martin F; Sharif-Rodriguez, Wanda; Zhu, Yonghua; Ruben, Zadok; Pan, Yi; Urosevic-Price, Olga; Wang, Li; Flattery, Amy M; Forrest, Gail; Szeto, Daphne; Zhao, Huawei; Roy, Sophie; Forrest, Michael J

    2011-01-01

    We investigated the effects of chronic mineralocorticoid receptor blockade with eplerenone on the development and progression of hypertension and end organ damage in Dahl salt-sensitive rats. Eplerenone significantly attenuated the progressive rise in systolic blood pressure (SBP) (204 ± 3 vs. 179±3 mmHg, p < 0.05), reduced proteinuria (605.5 ± 29.6 vs. 479.7 ± 26.1 mg/24h, p < 0.05), improved injury scores of glomeruli, tubules, renal interstitium, and vasculature in Dahl salt-sensitive rats fed a high-salt diet. These results demonstrate that mineralocorticoid receptor antagonism provides target organ protection and attenuates the development of elevated blood pressure (BP) in a model of salt-sensitive hypertension. PMID:21950654

  16. Role of renal medullary oxidative and/or carbonyl stress in salt-sensitive hypertension and diabetes.

    PubMed

    Mori, Takefumi; Ogawa, Susumu; Cowely, Allen W; Ito, Sadayoshi

    2012-01-01

    1. Salt-sensitive hypertension is commonly associated with diabetes, obesity and chronic kidney disease. The present review focuses on renal mechanisms involved in the development of this type of hypertension. 2. The renal medullary circulation plays an important role in the development of salt-sensitive hypertension. In vivo animal studies have demonstrated that the balance between nitric oxide (NO) and reactive oxygen species (ROS) in the renal medulla is an important element of salt-sensitive hypertension. The medullary thick ascending limb (mTAL) in the outer medulla is an important source of NO and ROS production and we have explored the mechanisms that stimulate their production, as well as the effects of NO superoxide and hydrogen peroxide on mTAL tubular sodium reabsorption and the regulation of medullary blood flow. 3. Angiotensin II-stimulated NO produced in the mTAL is able to diffuse from the renal mTAL to the surrounding vasa recta capillaries, providing a mechanism by which to increase medullary blood flow and counteract the direct vasoconstrictor effects of angiotensin II. Enhanced oxidative stress attenuates NO diffusion in this region. 4. Carbonyl stress, like oxidative stress, can also play an important role in the pathogenesis of chronic kidney disease, such as insulin resistance, salt-sensitive hypertension and renal vascular complications. 5. Despite the large number of studies undertaken in this area, there is as yet no drug available that directly targets renal ROS. Oxidative and/or carbonyl stress may be the next target of drug discovery to protect against salt-sensitive hypertension and associated end-organ damage. PMID:22150746

  17. [Hormonal profile and participation of nitric oxide in salt-sensitive and salt-resistant essential arterial hypertension].

    PubMed

    Gómez-Fernández, P; Moreno, V G; Cornejo, M; Vargas, J C; García-Barroso, C; Velasco, G; Almaraz, M

    2000-01-01

    results showed that patients with salt sensitive hypertension displayed a suppressed renin-aldosterone system, an attenuated nocturnal decline in blood pressure on high-salt diet and an impairment of endothelial function. The relationship between urinary nitrate excretion and arterial pressure suggest that the salt sensitivity of arterial pressure may be related bo blunted generation of endogenous nitric oxide. PMID:11100662

  18. Norepinephrine-evoked salt-sensitive hypertension requires impaired renal sodium chloride cotransporter activity in Sprague-Dawley rats.

    PubMed

    Walsh, Kathryn R; Kuwabara, Jill T; Shim, Joon W; Wainford, Richard D

    2016-01-15

    Recent studies have implicated a role of norepinephrine (NE) in the activation of the sodium chloride cotransporter (NCC) to drive the development of salt-sensitive hypertension. However, the interaction between NE and increased salt intake on blood pressure remains to be fully elucidated. This study examined the impact of a continuous NE infusion on sodium homeostasis and blood pressure in conscious Sprague-Dawley rats challenged with a normal (NS; 0.6% NaCl) or high-salt (HS; 8% NaCl) diet for 14 days. Naïve and saline-infused Sprague-Dawley rats remained normotensive when placed on HS and exhibited dietary sodium-evoked suppression of peak natriuresis to hydrochlorothiazide. NE infusion resulted in the development of hypertension, which was exacerbated by HS, demonstrating the development of the salt sensitivity of blood pressure [MAP (mmHg) NE+NS: 151 ± 3 vs. NE+HS: 172 ± 4; P < 0.05]. In these salt-sensitive animals, increased NE prevented dietary sodium-evoked suppression of peak natriuresis to hydrochlorothiazide, suggesting impaired NCC activity contributes to the development of salt sensitivity [peak natriuresis to hydrochlorothiazide (μeq/min) Naïve+NS: 9.4 ± 0.2 vs. Naïve+HS: 7 ± 0.1; P < 0.05; NE+NS: 11.1 ± 1.1; NE+HS: 10.8 ± 0.4). NE infusion did not alter NCC expression in animals maintained on NS; however, dietary sodium-evoked suppression of NCC expression was prevented in animals challenged with NE. Chronic NCC antagonism abolished the salt-sensitive component of NE-mediated hypertension, while chronic ANG II type 1 receptor antagonism significantly attenuated NE-evoked hypertension without restoring NCC function. These data demonstrate that increased levels of NE prevent dietary sodium-evoked suppression of the NCC, via an ANG II-independent mechanism, to stimulate the development of salt-sensitive hypertension. PMID:26608659

  19. [Role of renal inflammation in the physiopathology of salt-sensitive hypertension].

    PubMed

    Castro Torres, Yaniel; Santos Portela, Alejandro Emilio; Garrido Bősze, Ildiko María

    2014-01-01

    Salt-sensitive hypertension is produced by a decrease in salt renal excretion after a salt overload. Over the last few years, a new theory has been developed to explain this condition based on renal tissue inflammation. This process begins with free radicals production in renal tissue due to oxidative metabolism. Then they favor a renal inflammation mechanism with T-lymphocytes infiltration and other immune cells. Essentially, T-lymphocytes determine an increase in angiotensin ii production which raises sodium and water retention. Association among autoimmune diseases and hypertension may be explained, in part, by the relationship between salt-sensitive hypertension and renal inflammation. The use of antioxidant drugs and the development of new medicaments may be a choice for treating patients affected with this condition. PMID:25024004

  20. High Perfusion Pressure Accelerates Renal Injury in Salt-Sensitive Hypertension

    PubMed Central

    Mori, Takefumi; Polichnowski, Aaron; Glocka, Padden; Kaldunski, Mary; Ohsaki, Yusuke; Liang, Mingyu; Cowley, Allen W.

    2008-01-01

    Renal injury in the Dahl salt-sensitive rat mimics human salt-sensitive forms of hypertension that are particularly prevalent in black individuals, but the mechanisms that lead to the development of this injury are incompletely understood. We studied the impact of renal perfusion pressure (RPP) on the development of renal injury in this model. During the development of salt-induced hypertension over 2 wk, the RPP to the left kidney was maintained at control levels (125 ± 2 mmHg) by continuous servocontrol inflation of an aortic balloon implanted between the renal arteries; during the same period, the RPP to the right kidney rose to 164 ± 8 mmHg. After 2 wk of a 4% salt diet, DNA microarray and real-time PCR identified genes related to fibrosis and epithelial-to-mesenchymal transition in the kidneys exposed to hypertension. The increased RPP to the right kidney accounted for differences in renal injury between the two kidneys, measured by percentage of injured cortical and juxtamedullary glomeruli, quantified proteinaceous casts, number of ED-1–positive cells per glomerular tuft area, and interstitial fibrosis. Interlobular arteriolar injury was not increased in the kidney exposed to elevated pressure but was reduced in the control kidney. We conclude that elevations of RPP contribute significantly to the fibrosis and epithelial-to-mesenchymal transition found in the early phases of hypertension in the salt-sensitive rat. PMID:18417720

  1. Brain Gαi2-subunit proteins and the prevention of salt sensitive hypertension

    PubMed Central

    Carmichael, Casey Y.; Wainford, Richard D.

    2015-01-01

    To counter the development of salt-sensitive hypertension, multiple brain G-protein-coupled receptor (GPCR) systems are activated to facilitate sympathoinhibition, sodium homeostasis, and normotension. Currently there is a paucity of knowledge regarding the role of down-stream GPCR-activated Gα-subunit proteins in these critically important physiological regulatory responses required for long-term blood pressure regulation. We have determined that brain Gαi2-proteins mediate natriuretic and sympathoinhibitory responses produced by acute pharmacological (exogenous central nociceptin/orphanin FQ receptor (NOP) and α2-adrenoceptor activation) and physiological challenges to sodium homeostasis (intravenous volume expansion and 1 M sodium load) in conscious Sprague–Dawley rats. We have demonstrated that in salt-resistant rat phenotypes, high dietary salt intake evokes site-specific up-regulation of hypothalamic paraventricular nucleus (PVN) Gαi2-proteins. Further, we established that PVN Gαi2 protein up-regulation prevents the development of renal nerve-dependent sympathetically mediated salt-sensitive hypertension in Sprague–Dawley and Dahl salt-resistant rats. Additionally, failure to up-regulate PVN Gαi2 proteins during high salt-intake contributes to the pathophysiology of Dahl salt-sensitive (DSS) hypertension. Collectively, our data demonstrate that brain, and likely PVN specific, Gαi2 protein pathways represent a central molecular pathway mediating sympathoinhibitory renal-nerve dependent responses evoked to maintain sodium homeostasis and a salt-resistant phenotype. Further, impairment of this endogenous “anti-hypertensive” mechanism contributes to the pathophysiology of salt-sensitive hypertension. PMID:26347659

  2. Targeting Interleukin-1 beta to Suppress Sympathoexcitation in Hypothalamic Paraventricular Nucleus in Dahl Salt-Sensitive Hypertensive Rats.

    PubMed

    Qi, Jie; Zhao, Xiu-Fang; Yu, Xiao-Jing; Yi, Qiu-Yue; Shi, Xiao-Lian; Tan, Hong; Fan, Xiao-Yan; Gao, Hong-Li; Yue, Li-Ying; Feng, Zhi-Peng; Kang, Yu-Ming

    2016-07-01

    Findings from our laboratory indicate that expressions of some proinflammatory cytokines such as tumor necrosis factor, interleukin-6 and oxidative stress responses are increased in the hypothalamic paraventricular nucleus (PVN) and contribute to the progression of salt-sensitive hypertension. In this study, we determined whether interleukin-1 beta (IL-1β) activation within the PVN contributes to sympathoexcitation during development of salt-dependent hypertension. Eight-week-old male Dahl salt-sensitive (S) rats received a high-salt diet (HS, 8 % NaCl) or a normal-salt diet (NS, 0.3 % NaCl) for 6 weeks, and all rats were treated with bilateral PVN injection of gevokizumab (IL-1β inhibitor, 1 μL of 10 μg) or vehicle once a week. The mean arterial pressure (MAP), heart rate (HR) and plasma norepinephrine (NE) were significantly increased in high-salt-fed rats. In addition, rats with high-salt diet had higher levels of NOX-2, NOX-4 [subunits of NAD (P) H oxidase], IL-1β, NLRP3 (NOD-like receptor family pyrin domain containing 3), Fra-LI (an indicator of chronic neuronal activation) and lower levels of IL-10 in the PVN than normal-diet rats. Bilateral PVN injection of gevokizumab decreased MAP, HR and NE, attenuated the levels of oxidative stress and restored the balance of cytokines. These findings suggest that IL-1β activation in the PVN plays a role in salt-sensitive hypertension. PMID:26304161

  3. Genetic Decreases in Atrial Natriuretic Peptide and Salt-Sensitive Hypertension

    NASA Astrophysics Data System (ADS)

    John, Simon W. M.; Krege, John H.; Oliver, Paula M.; Hagaman, John R.; Hodgin, Jeffrey B.; Pang, Stephen C.; Flynn, T. Geoffrey; Smithies, Oliver

    1995-02-01

    To determine if defects in the atrial natriuretic peptide (ANP) system can cause hypertension, mice were generated with a disruption of the proANP gene. Homozygous mutants had no circulating or atrial ANP, and their blood pressures were elevated by 8 to 23 millimeters of mercury when they were fed standard (0.5 percent sodium chloride) and intermediate (2 percent sodium chloride) salt diets. On standard salt diets, heterozygotes had normal amounts of circulating ANP and normal blood pressures. However, on high (8 percent sodium chloride) salt diets they were hypertensive, with blood pressures elevated by 27 millimeters of mercury. These results demonstrate that genetically reduced production of ANP can lead to salt-sensitive hypertension.

  4. Inhibition of cyclooxygenase-2 in hematopoietic cells results in salt-sensitive hypertension

    PubMed Central

    Zhang, Ming-Zhi; Yao, Bing; Wang, Yinqiu; Yang, Shilin; Wang, Suwan; Fan, Xiaofeng; Harris, Raymond C.

    2015-01-01

    Inhibition of prostaglandin (PG) production with either nonselective or selective inhibitors of cyclooxygenase-2 (COX-2) activity can induce or exacerbate salt-sensitive hypertension. This effect has been previously attributed to inhibition of intrinsic renal COX-2 activity and subsequent increase in sodium retention by the kidney. Here, we found that macrophages isolated from kidneys of high-salt–treated WT mice have increased levels of COX-2 and microsomal PGE synthase–1 (mPGES-1). Furthermore, BM transplantation (BMT) from either COX-2–deficient or mPGES-1–deficient mice into WT mice or macrophage-specific deletion of the PGE2 type 4 (EP4) receptor induced salt-sensitive hypertension and increased phosphorylation of the renal sodium chloride cotransporter (NCC). Kidneys from high-salt–treated WT mice transplanted with Cox2–/– BM had increased macrophage and T cell infiltration and increased M1- and Th1-associated markers and cytokines. Skin macrophages from high-salt–treated mice with either genetic or pharmacologic inhibition of the COX-2 pathway expressed decreased M2 markers and VEGF-C production and exhibited aberrant lymphangiogenesis. Together, these studies demonstrate that COX-2–derived PGE2 in hematopoietic cells plays an important role in both kidney and skin in maintaining homeostasis in response to chronically increased dietary salt. Moreover, these results indicate that inhibiting COX-2 expression or activity in hematopoietic cells can result in a predisposition to salt-sensitive hypertension. PMID:26485285

  5. Macula Densa Nitric Oxide Synthase 1β Protects against Salt-Sensitive Hypertension.

    PubMed

    Lu, Yan; Wei, Jin; Stec, David E; Roman, Richard J; Ge, Ying; Cheng, Liang; Liu, Eddie Y; Zhang, Jie; Hansen, Pernille B Laerkegaard; Fan, Fan; Juncos, Luis A; Wang, Lei; Pollock, Jennifer; Huang, Paul L; Fu, Yiling; Wang, Shaohui; Liu, Ruisheng

    2016-08-01

    Nitric oxide (NO) is an important negative modulator of tubuloglomerular feedback responsiveness. We recently found that macula densa expresses α-, β-, and γ-splice variants of neuronal nitric oxide synthase 1 (NOS1), and NOS1β expression in the macula densa increases on a high-salt diet. This study tested whether upregulation of NOS1β expression in the macula densa affects sodium excretion and salt-sensitive hypertension by decreasing tubuloglomerular feedback responsiveness. Expression levels of NOS1β mRNA and protein were 30- and five-fold higher, respectively, than those of NOS1α in the renal cortex of C57BL/6 mice. Furthermore, macula densa NO production was similar in the isolated perfused juxtaglomerular apparatus of wild-type (WT) and nitric oxide synthase 1α-knockout (NOS1αKO) mice. Compared with control mice, mice with macula densa-specific knockout of all nitric oxide synthase 1 isoforms (MD-NOS1KO) had a significantly enhanced tubuloglomerular feedback response and after acute volume expansion, significantly reduced GFR, urine flow, and sodium excretion. Mean arterial pressure increased significantly in MD-NOS1KO mice (P<0.01) but not NOS1flox/flox mice fed a high-salt diet. After infusion of angiotensin II, mean arterial pressure increased by 61.6 mmHg in MD-NOS1KO mice versus 32.0 mmHg in WT mice (P<0.01) fed a high-salt diet. These results indicate that NOS1β is a primary NOS1 isoform expressed in the macula densa and regulates the tubuloglomerular feedback response, the natriuretic response to acute volume expansion, and the development of salt-sensitive hypertension. These findings show a novel mechanism for salt sensitivity of BP and the significance of tubuloglomerular feedback response in long-term control of sodium excretion and BP. PMID:26647426

  6. The protective effect of Liu-Wei-Di-Huang-Fang in salt-sensitive hypertension rats.

    PubMed

    Yang, Qiang; He, Yanming; Wang, Wenjian

    2014-01-01

    Abstract Hypertension is considered as a chronic and complex disease relating to multiple systemic systems. Apart from lowering blood pressure, the final purpose of the treatment lies in reducing the variability of blood pressure and other risk factors. Traditional Chinese medicine (TCM) has a long history of treating hypertension. This study was designed to determine the effect of Liu-Wei-Di-Huang-Fang (L-W-D-H-F), a compound used in traditional Chinese herbal medicine, to treat salt-sensitive hypertension (SSHT) induced by a high-salt and high-fat diet. L-W-D-H-F was prepared from six plant extracts. It was dissolved in 0.9% sodium chloride solution prior to use. Male Sprague-Dawley (6 weeks) rats were randomly divided into four groups: normal diet (CON); HSF (Without Drug Intervention); VAL (Valsartan 13.33 mg/kg/day); and LW (L-W-D-H-F 8.13 g/kg/day). Six weeks after blood pressure treatment, plasma biochemical analyses and histological and functional examination of the kidney were performed. L-W-D-H-F decreased the levels of mean arterial pressure (MAP), fasting blood glucose (FG), insulin (INS), high-density lipoprotein cholesterol (HDL-c), homeostasis model assessment of basal insulin resistance (HOMA-IR) and angiotensin II (Ang II) from plasma and Ang II and renin from kidney. It also promoted the excretion of urinary Na(+), reducing the loss of urinary K(+) and microalbuminuria (MAU), and improved the glomerular afferent arteriole, arterioles and each kidney unit. Together, these results suggest that L-W-D-H-F is capable of moderately reducing MAP in salt-sensitive hypertension and can work at different levels on multiple differential targets. PMID:24164386

  7. The role of mineralocorticoid action in the brain in salt-sensitive hypertension

    PubMed Central

    Oki, Kenji; Gomez-Sanchez, Elise P.; Gomez-Sanchez, Celso E.

    2011-01-01

    Summary 1. The mechanisms by which excessive salt causes hypertension involve more than retention of sodium and water by the kidneys and are far from clear. Mineralocorticoids act centrally to increase salt appetite, sympathetic drive and vasopressin release, resulting in hypertension that is prevented by the central infusion of mineralocorticoid receptor (MR) antagonists. The MR has similar affinity for aldo and the glucocorticoids corticosterone or cortisol. Specificity is conferred in transport epithelia by the co-localization of the MR with 11β-hydroxysteroid dehydrogenase type 2. Co-expression also occurs in some neurons, notably those of the nucleus tractus solitarius that are activated by sodium depletion and aldo and mediate salt seeking behavior. 2. The salt-induced hypertension of the Dahl Salt Sensitive rat is mitigated by the central infusion of a mineralocorticoid antagonist even though circulating aldo is normal or reduced in SS. Contrary to reports that salt appetite in the SS rat is depressed, we found that it is increased compared to the Spraque-Dawley (SD). 3. Extra-adrenal aldo synthesis in the brain occurs in minute amounts that could only be relevant locally. mRNA for aldo synthase enzyme and aldo concentration in the brain of the Dahl SS are increased compared to SD rats. The central infusion of inhibitors of aldo synthesis lowers salt-induced hypertension in the SS, suggesting a role for excessive aldo synthesis in the brain. Brain MR, particularly those in the PVN, regulate inflammatory processes that are exacerbated by sodium and lead to cardiovascular dysfunction. PMID:21585422

  8. Pappa2 is linked to salt-sensitive hypertension in Dahl S rats.

    PubMed

    Cowley, Allen W; Yang, Chun; Kumar, Vikash; Lazar, Jozef; Jacob, Howard; Geurts, Aron M; Liu, Pengyuan; Dayton, Alex; Kurth, Theresa; Liang, Mingyu

    2016-01-01

    A 1.37 Mbp region of chromosome 13 previously identified by exclusion mapping was consistently associated with a reduction of salt-induced hypertension in the Dahl salt-sensitive (SS) rat. This region contained five genes that were introgressed from the salt-insensitive Brown Norway (BN) rat. The goal of the present study was to further narrow that region to identify the gene(s) most likely to protect from salt-induced hypertension. The studies yielded a subcongenic SS rat strain containing a 0.71 Mbp insert from BN (26-P strain) in which salt-induced hypertension was reduced by 24 mmHg. The region contained two protein-coding genes (Astn1 and Pappa2) and a microRNA (miR-488). Pappa2 mRNA in the renal cortex of the protected 26-P was 6- to 10-fold greater than in SS fed a 0.4% NaCl diet but was reduced to levels observed in SS when fed 8.0% NaCl diet for 7 days. Compared with brain nuclei (NTS, RVLM, CVLM) and the adrenal gland, Pappa2 in the renal cortex was the only gene found to be differentially expressed between SS and 26-P and that responded to changes of salt diet. Immunohistochemistry studies found Pappa2 localized in the cytosol of the epithelial cells of the cortical thick ascending limbs. In more distal segments of the renal tubules, it was observed within tubular lumens and most notably bound to the apical membranes of the intercalated cells of collecting ducts. We conclude that we have identified a variant form of Pappa2 that can protect against salt-induced hypertension in the Dahl S rat. PMID:26534937

  9. Evidence of the Importance of Nox4 in Production of Hypertension in Dahl Salt-Sensitive Rats.

    PubMed

    Cowley, Allen W; Yang, Chun; Zheleznova, Nadezhda N; Staruschenko, Alexander; Kurth, Theresa; Rein, Lisa; Kumar, Vikash; Sadovnikov, Katherine; Dayton, Alex; Hoffman, Matthew; Ryan, Robert P; Skelton, Meredith M; Salehpour, Fahimeh; Ranji, Mahsa; Geurts, Aron

    2016-02-01

    This study reports the consequences of knocking out NADPH (nicotinamide adenine dinucleotide phosphate) oxidase 4 (Nox4) on the development of hypertension and kidney injury in the Dahl salt-sensitive (SS) rat. Zinc finger nuclease injection of single-cell SS embryos was used to create an 8 base-pair frame-shift deletion of Nox4, resulting in a loss of the ≈68 kDa band in Western blot analysis of renal cortical tissue of the knock out of Nox4 in the SS rat (SS(Nox4-/-)) rats. SS(Nox4-/-) rats exhibited a significant reduction of salt-induced hypertension compared with SS rats after 21 days of 4.0% NaCl diet (134±5 versus 151±3 mm Hg in SS) and a significant reduction of albuminuria, tubular casts, and glomerular injury. Optical fluorescence 3-dimensional cryoimaging revealed significantly higher redox ratios (NADH/FAD [reduced nicotinamide adenine dinucleotide/flavin adenine dinucleotide]) in the kidneys of SS(Nox4-/-) rats even when fed the 0.4% NaCl diet, indicating greater levels of mitochondrial electron transport chain metabolic activity and reduced oxidative stress compared with SS rats. Before the development of hypertension, RNA expression levels of Nox subunits Nox2, p67(phox), and p22(phox) were found to be significantly lower (P<0.05) in SS(Nox4-/-) compared with SS rats in the renal cortex. Thus, the mutation of Nox4 seems to modify transcription of several genes in ways that contribute to the protective effects observed in the SS(Nox4-/-) rats. We conclude that the reduced renal injury and attenuated blood pressure response to high salt in the SS(Nox4-/-) rat could be the result of multiple pathways, including gene transcription, mitochondrial energetics, oxidative stress, and protein matrix production impacted by the knock out of Nox4. PMID:26644237

  10. Glucose-independent renoprotective mechanisms of the tissue dipeptidyl peptidase-4 inhibitor, saxagliptin, in Dahl salt-sensitive hypertensive rats.

    PubMed

    Uchii, Masako; Kimoto, Naoya; Sakai, Mariko; Kitayama, Tetsuya; Kunori, Shunji

    2016-07-15

    Although previous studies have shown an important role of renal dipeptidyl peptidase-4 (DPP-4) inhibition in ameliorating kidney injury in hypertensive rats, the renal distribution of DPP-4 and mechanisms of renoprotective action of DPP-4 inhibition remain unclear. In this study, we examined the effects of the DPP-4 inhibitor saxagliptin on DPP-4 activity in renal cells (using in situ DPP-4 staining) and on renal gene expression related to inflammation and fibrosis in the renal injury in hypertensive Dahl salt-sensitive (Dahl-S) rats. Male rats fed a high-salt (8% NaCl) diet received vehicle (water) or saxagliptin (12.7mg/kg/day) for 4 weeks. Blood pressure (BP), serum glucose and 24-h urinary albumin and sodium excretions were measured, and renal histopathology was performed. High salt-diet increased BP and urinary albumin excretion, consequently resulting in glomerular sclerosis and tubulointerstitial fibrosis. Although saxagliptin did not affect BP and blood glucose levels, it significantly ameliorated urinary albumin excretion. In situ staining showed DPP-4 activity in glomerular and tubular cells. Saxagliptin significantly suppressed DPP-4 activity in renal tissue extracts and in glomerular and tubular cells. Saxagliptin also significantly attenuated the increase in inflammation and fibrosis-related gene expressions in the kidney. Our results demonstrate that saxagliptin inhibited the development of renal injury independent of its glucose-lowering effect. Glomerular and tubular DPP-4 inhibition by saxagliptin was associated with improvements in albuminuria and the suppression of inflammation and fibrosis-related genes. Thus, local glomerular and tubular DPP-4 inhibition by saxagliptin may play an important role in its renoprotective effects in Dahl-S rats. PMID:27063445

  11. Dietary protein source determines the degree of hypertension and renal disease in the Dahl salt-sensitive rat.

    PubMed

    Mattson, David L; Meister, Carla J; Marcelle, Michelle L

    2005-04-01

    Previous studies demonstrated that a whole-grain diet attenuated sodium-dependent hypertension and renal disease in Dahl salt-sensitive rats from the colony at the Medical College of Wisconsin (Dahl SS/Mcw rats) compared with rats maintained on a purified AIN-76A diet. The present experiments determined which component(s) of the grain diet prevented renal and cardiovascular disease. Male SS/Mcw rats were maintained on isocaloric diets identical to AIN-76A, except the source of protein (wheat gluten for casein), carbohydrate (wheat flour for sucrose), or fat (soybean oil for corn oil) was substituted in separate diets. Rats were maintained on the different diets from weaning and studied after 3 weeks on a high-salt (4.0% NaCl) diet. Substitution of the carbohydrate in the diet did not affect body weight, arterial pressure, or renal disease. Replacement of casein with wheat gluten significantly reduced body weight (258+/-7 versus 353+/-3 grams), mean arterial pressure (133+/-2 versus 153+/-2 mm Hg), and albumin excretion (9+/-1 versus 50+/-7 mg/d) to levels of rats fed the whole-grain diet (n=7 to 16/group). Replacement of the fat in the diet increased arterial pressure without affecting body weight or albumin excretion. The results of the present study indicate that dietary components other than sodium play an important role in the development of hypertension and renal disease in the Dahl SS/Mcw rat. PMID:15699463

  12. Angiotensin AT2 receptor agonist prevents salt-sensitive hypertension in obese Zucker rats.

    PubMed

    Ali, Quaisar; Patel, Sanket; Hussain, Tahir

    2015-06-15

    High-sodium intake is a risk factor for the pathogenesis of hypertension, especially in obesity. The present study is designed to investigate whether angiotensin type 2 receptor (AT2R) activation with selective agonist C21 prevents high-sodium diet (HSD)-induced hypertension in obese animals. Male obese rats were treated with AT2R agonist C21 (1 mg·kg(-1)·day(-1), oral) while maintained on either normal-sodium diet (NSD; 0.4%) or HSD (4%) for 2 wk. Radiotelemetric recording showed a time-dependent increase in systolic blood pressure in HSD-fed obese rats, being maximal increase (∼27 mmHg) at day 12 of the HSD regimen. C21 treatment completely prevented the increase in blood pressure of HSD-fed rats. Compared with NSD controls, HSD-fed obese rats had greater natriuresis/diuresis and urinary levels of nitrates, and these parameters were further increased by C21 treatment. Also, C21 treatment improved glomerular filtration rate in HSD-fed rats. HSD-fed rats expressed higher level of cortical ANG II, which was reduced to 50% by C21 treatment. HSD feeding and/or C21 treatment had no effects on cortical renin activity and the expression of angiotensin-converting enzyme (ACE) and chymase, which are ANG II-producing enzymes. However, ANG(1-7) concentration and ACE2 activity in the renal cortex were reduced by HSD feeding, and C21 treatment rescued both the parameters. Also, C21 treatment reduced the cortical expression of AT1R in HSD-fed rats, but had no effect of AT2R expression. We conclude that chronic treatment with the AT2R agonist C21 prevents salt-sensitive hypertension in obese rats, and a reduction in the renal ANG II/AT1R and enhanced ACE2/ANG(1-7) levels may play a potential role in this phenomenon. PMID:25855512

  13. Salt-sensitive hypertension and cardiac hypertrophy in transgenic mice expressing a corin variant identified in blacks.

    PubMed

    Wang, Wei; Cui, Yujie; Shen, Jianzhong; Jiang, Jingjing; Chen, Shenghan; Peng, Jianhao; Wu, Qingyu

    2012-11-01

    Blacks represent a high-risk population for salt-sensitive hypertension and heart disease, but the underlying mechanism remains unclear. Corin is a cardiac protease that regulates blood pressure by activating natriuretic peptides. A corin gene variant (T555I/Q568P) was identified in blacks with hypertension and cardiac hypertrophy. In this study, we tested the hypothesis that the corin variant contributes to the hypertensive and cardiac hypertrophic phenotype in vivo. Transgenic mice were generated to express wild-type (WT) or T555I/Q568P variant corin in the heart under the control of α-myosin heavy chain promoter. The mice were crossed into a corin knockout (KO) background to create KO/TgWT and KO/TgV mice that expressed WT or variant corin, respectively, in the heart. Functional studies showed that KO/TgV mice had significantly higher levels of proatrial natriuretic peptide in the heart compared with that in control KO/TgWT mice, indicating that the corin variant was defective in processing natriuretic peptides in vivo. By radiotelemetry, corin KO/TgV mice were found to have hypertension that was sensitive to dietary salt loading. The mice also developed cardiac hypertrophy at 12 to 14 months of age when fed a normal salt diet or at a younger age when fed a high-salt diet. The phenotype of salt-sensitive hypertension and cardiac hypertrophy in KO/TgV mice closely resembles the pathological findings in blacks who carry the corin variant. The results indicate that corin defects may represent an important mechanism in salt-sensitive hypertension and cardiac hypertrophy in blacks. PMID:22987923

  14. Salt-sensitive hypertension is associated with dysfunctional Cyp4a10 gene and kidney epithelial sodium channel

    PubMed Central

    Nakagawa, Kiyoshi; Holla, Vijaykumar R.; Wei, Yuan; Wang, Wen-Hui; Gatica, Arnaldo; Wei, Shouzou; Mei, Shaojun; Miller, Crystal M.; Cha, Dae Ryong; Price, Edward; Zent, Roy; Pozzi, Ambra; Breyer, Matthew D.; Guan, Youfei; Falck, John R.; Waterman, Michael R.; Capdevila, Jorge H.

    2006-01-01

    Functional and biochemical data have suggested a role for the cytochrome P450 arachidonate monooxygenases in the pathophysiology of hypertension, a leading cause of cardiovascular, cerebral, and renal morbidity and mortality. We show here that disruption of the murine cytochrome P450, family 4, subfamily a, polypeptide 10 (Cyp4a10) gene causes a type of hypertension that is, like most human hypertension, dietary salt sensitive. Cyp4a10–/– mice fed low-salt diets were normotensive but became hypertensive when fed normal or high-salt diets. Hypertensive Cyp4a10–/– mice had a dysfunctional kidney epithelial sodium channel and became normotensive when administered amiloride, a selective inhibitor of this sodium channel. These studies (a) establish a physiological role for the arachidonate monooxygenases in renal sodium reabsorption and blood pressure regulation, (b) demonstrate that a dysfunctional Cyp4a10 gene causes alterations in the gating activity of the kidney epithelial sodium channel, and (c) identify a conceptually novel approach for studies of the molecular basis of human hypertension. It is expected that these results could lead to new strategies for the early diagnosis and clinical management of this devastating disease. PMID:16691295

  15. Proton channels and renal hypertensive injury: a key piece of the Dahl salt-sensitive rat puzzle?

    PubMed

    O'Connor, Paul M; Guha, Avirup; Stilphen, Carly A; Sun, Jingping; Jin, Chunhua

    2016-04-15

    Hv1 is a voltage-gated proton channel highly expressed in phagocytic cells, where it participates in the NADPH oxidase-dependent respiratory burst. We have recently identified Hv1 as a novel renal channel, expressed in the renal medullary thick ascending limb that appears to importantly contribute to the pathogenesis of renal hypertensive injury in the Dahl salt-sensitive rat model. The purpose of this review is to describe the experimental approaches that we have undertaken to identify the source of excess reactive oxygen species production in the renal outer medulla of Dahl salt-sensitive rats and the resulting evidence that the voltage-gated proton channel Hv1 mediates augmented superoxide production and contributes to renal medullary oxidative stress and renal injury. In addition, we will attempt to point out areas of current controversy, as well as propose areas in which further experimental studies are likely to move the field forward. The content of the following review was presented as part of the Water and Electrolyte Homeostasis Section New Investigator Award talk at Experimental Biology 2014. PMID:26843580

  16. Does a medical history of hypertension influence disclosing genetic testing results of the risk for salt-sensitive hypertension, in primary care?

    PubMed Central

    Okayama, Masanobu; Takeshima, Taro; Harada, Masanori; Ae, Ryusuke; Kajii, Eiji

    2016-01-01

    Objective Disclosing genetic testing results may contribute to the prevention and management of many common diseases. However, whether the presence of a disease influences these effects is unclear. This study aimed to clarify the difference in the effects of disclosing genetic testing results of the risk for developing salt-sensitive hypertension on the behavioral modifications with respect to salt intake in hypertensive and nonhypertensive patients. Methods A cross-sectional study using a self-administered questionnaire was conducted for outpatients aged >20 years (N=2,237) at six primary care clinics and hospitals in Japan. The main factors assessed were medical histories of hypertension, salt preferences, reduced salt intakes, and behavior modifications for reducing salt intake. Behavioral modifications of participants were assessed using their behavior stages before and after disclosure of the hypothetical genetic testing results. Results Of the 2,237 participants, 1,644 (73.5%) responded to the survey. Of these respondents, 558 (33.9%) patients were hypertensive and 1,086 (66.1%) were nonhypertensive. After being notified of the result “If with genetic risk”, the nonhypertensive participants were more likely to make positive behavioral modifications compared to the hypertensive patients among all participants and in those aged <65 years (adjusted relative ratio [ad-RR], 1.76; 95% confidence interval, 1.12−2.76 and ad-RR, 1.99; 1.11−3.57, respectively). In contrast, no difference in negative behavioral modifications between hypertensive and nonhypertensive patients was detected after being notified of the result “If without genetic risk” (ad-RR, 1.05; 95% confidence interval, 0.70−1.57). Conclusion The behavior of modifying salt intake after disclosure of the genetic testing results differed between hypertensive and nonhypertensive patients. Disclosing a genetic risk for salt-sensitive hypertension was likely to cause nonhypertensive patients

  17. Gene expression responses of threespine stickleback to salinity: implications for salt-sensitive hypertension

    PubMed Central

    Wang, Gang; Yang, Ence; Smith, Kerri J.; Zeng, Yong; Ji, Guoli; Connon, Richard; Fangue, Nann A.; Cai, James J.

    2014-01-01

    Despite recent success with genome-wide association studies (GWAS), identifying hypertension (HTN)-susceptibility loci in the general population remains difficult. Here, we present a novel strategy to address this challenge by studying salinity adaptation in the threespine stickleback, a fish species with diverse salt-handling ecotypes. We acclimated native freshwater (FW) and anadromous saltwater (SW) threespine sticklebacks to fresh, brackish, and sea water for 30 days, and applied RNA sequencing to determine the gene expression in fish kidneys. We identified 1844 salt-responsive genes that were differentially expressed between FW sticklebacks acclimated to different salinities and/or between SW and FW sticklebacks acclimated to full-strength sea water. Significant overlap between stickleback salt-responsive genes and human genes implicated in HTN was detected (P < 10−7, hypergeometric test), suggesting a possible similarity in genetic mechanisms of salt handling between threespine sticklebacks and humans. The overlapping genes included a newly discovered HTN gene—MAP3K15, whose expression in FW stickleback kidneys decreases with salinity. These also included genes located in the GWAS loci such as AGTRAP-PLOD1 and CYP1A1-ULK3, which contain multiple potentially causative genes contributing to HTN susceptibility that need to be prioritized for study. Taken together, we show that stickleback salt-responsive genes provide valuable information facilitating the identification of human HTN genes. Thus, threespine sticklebacks may be used as a model, complementary to existing animal models, in human HTN research. PMID:25309574

  18. Gene expression responses of threespine stickleback to salinity: implications for salt-sensitive hypertension.

    PubMed

    Wang, Gang; Yang, Ence; Smith, Kerri J; Zeng, Yong; Ji, Guoli; Connon, Richard; Fangue, Nann A; Cai, James J

    2014-01-01

    Despite recent success with genome-wide association studies (GWAS), identifying hypertension (HTN)-susceptibility loci in the general population remains difficult. Here, we present a novel strategy to address this challenge by studying salinity adaptation in the threespine stickleback, a fish species with diverse salt-handling ecotypes. We acclimated native freshwater (FW) and anadromous saltwater (SW) threespine sticklebacks to fresh, brackish, and sea water for 30 days, and applied RNA sequencing to determine the gene expression in fish kidneys. We identified 1844 salt-responsive genes that were differentially expressed between FW sticklebacks acclimated to different salinities and/or between SW and FW sticklebacks acclimated to full-strength sea water. Significant overlap between stickleback salt-responsive genes and human genes implicated in HTN was detected (P < 10(-7), hypergeometric test), suggesting a possible similarity in genetic mechanisms of salt handling between threespine sticklebacks and humans. The overlapping genes included a newly discovered HTN gene-MAP3K15, whose expression in FW stickleback kidneys decreases with salinity. These also included genes located in the GWAS loci such as AGTRAP-PLOD1 and CYP1A1-ULK3, which contain multiple potentially causative genes contributing to HTN susceptibility that need to be prioritized for study. Taken together, we show that stickleback salt-responsive genes provide valuable information facilitating the identification of human HTN genes. Thus, threespine sticklebacks may be used as a model, complementary to existing animal models, in human HTN research. PMID:25309574

  19. Intermittent electrical stimulation of the right cervical vagus nerve in salt-sensitive hypertensive rats: effects on blood pressure, arrhythmias, and ventricular electrophysiology

    PubMed Central

    Annoni, Elizabeth M; Xie, Xueyi; Lee, Steven W; Libbus, Imad; KenKnight, Bruce H; Osborn, John W; Tolkacheva, Elena G

    2015-01-01

    Hypertension (HTN) is the single greatest risk factor for potentially fatal cardiovascular diseases. One cause of HTN is inappropriately increased sympathetic nervous system activity, suggesting that restoring the autonomic nervous balance may be an effective means of HTN treatment. Here, we studied the potential of vagus nerve stimulation (VNS) to treat chronic HTN and cardiac arrhythmias through stimulation of the right cervical vagus nerve in hypertensive rats. Dahl salt-sensitive rats (n = 12) were given a high salt diet to induce HTN. After 6 weeks, rats were randomized into two groups: HTN-Sham and HTN-VNS, in which VNS was provided to HTN-VNS group for 4 weeks. In vivo blood pressure and electrocardiogram activities were monitored continuously by an implantable telemetry system. After 10 weeks, rats were euthanized and their hearts were extracted for ex vivo electrophysiological studies using high-resolution optical mapping. Six weeks of high salt diet significantly increased both mean arterial pressure (MAP) and pulse pressure, demonstrating successful induction of HTN in all rats. After 4 weeks of VNS treatment, the increase in MAP and the number of arrhythmia episodes in HTN-VNS rats was significantly attenuated when compared to those observed in HTN-Sham rats. VNS treatment also induced changes in electrophysiological properties of the heart, such as reduction in action potential duration (APD) during rapid drive pacing, slope of APD restitution, spatial dispersion of APD, and increase in conduction velocity of impulse propagation. Overall, these results provide further evidence for the therapeutic efficacy of VNS in HTN and HTN-related heart diseases. PMID:26265746

  20. Inhibition of Nitric Oxide Synthase 1 Induces Salt-Sensitive Hypertension in Nitric Oxide Synthase 1α Knockout and Wild-Type Mice.

    PubMed

    Wang, Ximing; Chandrashekar, Kiran; Wang, Lei; Lai, En Yin; Wei, Jin; Zhang, Gensheng; Wang, Shaohui; Zhang, Jie; Juncos, Luis A; Liu, Ruisheng

    2016-04-01

    We recently showed that α, β, and γ splice variants of neuronal nitric oxide synthase (NOS1) expressed in the macula densa and NOS1β accounts for most of the NO generation. We have also demonstrated that the mice with deletion of NOS1 specifically from the macula densa developed salt-sensitive hypertension. However, the global NOS1 knockout (NOS1KO) strain is neither hypertensive nor salt sensitive. This global NOS1KO strain is actually an NOS1αKO model. Consequently, we hypothesized that inhibition of NOS1β in NOS1αKO mice induces salt-sensitive hypertension. NOS1αKO and C57BL/6 wild-type (WT) mice were implanted with telemetry transmitters and divided into 7-nitroindazole (10 mg/kg/d)-treated and nontreated groups. All of the mice were fed a normal salt (0.4% NaCl) diet for 5 days, followed by a high-salt diet (4% NaCl). NO generation by the macula densa was inhibited by >90% in WT and NOS1αKO mice treated with 7-nitroindazole. Glomerular filtration rate in conscious mice was increased by ≈40% after a high-salt diet in both NOS1αKO and WT mice. In response to acute volume expansion, glomerular filtration rate, diuretic and natriuretic response were significantly blunted in the WT and knockout mice treated with 7-nitroindazole. Mean arterial pressure had no significant changes in mice fed a high-salt diet, but increased ≈15 mm Hg similarly in NOS1αKO and WT mice treated with 7-nitroindazole. We conclude that NOS1β, but not NOS1α, plays an important role in control of sodium excretion and hemodynamics in response to either an acute or a chronic salt loading. PMID:26883268

  1. Mononuclear phagocyte system depletion blocks interstitial tonicity-responsive enhancer binding protein/vascular endothelial growth factor C expression and induces salt-sensitive hypertension in rats.

    PubMed

    Machnik, Agnes; Dahlmann, Anke; Kopp, Christoph; Goss, Jennifer; Wagner, Hubertus; van Rooijen, Nico; Eckardt, Kai-Uwe; Müller, Dominik N; Park, Joon-Keun; Luft, Friedrich C; Kerjaschki, Dontscho; Titze, Jens

    2010-03-01

    We showed recently that mononuclear phagocyte system (MPS) cells provide a buffering mechanism for salt-sensitive hypertension by driving interstitial lymphangiogenesis, modulating interstitial Na(+) clearance, and increasing endothelial NO synthase protein expression in response to very high dietary salt via a tonicity-responsive enhancer binding protein/vascular endothelial growth factor C regulatory mechanism. We now tested whether isotonic saline and deoxycorticosterone acetate (DOCA)-salt treatment leads to a similar regulatory response in Sprague-Dawley rats. Male rats were fed a low-salt diet and received tap water (low-salt diet LSD), 1.0% saline (high-salt diet HSD), or DOCA+1.0% saline (DOCA-HSD). To test the regulatory role of interstitial MPS cells, we further depleted MPS cells with clodronate liposomes. HSD and DOCA-HSD led to Na(+) accumulation in the skin, MPS-driven tonicity-responsive enhancer binding protein/vascular endothelial growth factor C-mediated hyperplasia of interstitial lymph capillaries, and increased endothelial NO synthase protein expression in skin interstitium. Clodronate liposome MPS cell depletion blocked MPS infiltration in the skin interstitium, resulting in unchanged tonicity-responsive enhance binding protein/vascular endothelial growth factor C levels and absent hyperplasia of the lymph capillary network. Moreover, no increased skin endothelial NO synthase protein expression occurred in either clodronate liposome-treated HSD or DOCA-salt rats. Thus, absence of the MPS-cell regulatory response converted a salt-resistant blood-pressure state to a salt-sensitive state in HSD rats. Furthermore, salt-sensitive hypertension in DOCA-salt rats was aggravated. We conclude that MPS cells act as onsite controllers of interstitial volume and blood pressure homeostasis, providing a local regulatory salt-sensitive tonicity-responsive enhancer binding protein/vascular endothelial growth factor C-mediated mechanism in the skin to maintain

  2. Endothelin-1 critically contribute to EPC reduction and dysfunction via an ETA/NADPH oxidase pathway-induced oxidative stress in salt-sensitive hypertension

    PubMed Central

    Chen, Dan-Dan; Dong, Yu-Gang; Chen, Alex F.

    2012-01-01

    Circulating endothelial progenitor cells (EPCs) are reduced in hypertension, which inversely correlates with its mortality. DOCA–salt hypertension features elevated ET-1 and oxidative stress. We tested the hypothesis that ET-1 induces EPC dysfunction by elevating oxidative stress through the ETA/NADPH oxidase pathway in salt-sensitive hypertension. Both ETA and ETB receptors were expressed in EPCs, but only ETA receptors were significantly increased in EPCs of DOCA-salt rats. EPC number and function were reduced in DOCA-salt rats compared with Sham controls, both were reversed by in vivo blockade of ETA receptors or NADPH oxidase. The enzymatic activity of NAPDH oxidase and its subunits gp91phox, p22phox and Rac1 were augmented in EPCs of DOCA-salt rats, with concomitantly decreased antioxidant enzymes MnSOD, CuZnSOD, and GPx-1. ROS level was elevated in EPCs from DOCA-salt rats, accompanied by increased EPC telomerase inactivation, senescence and apoptosis, which were rescued by ETA or NADPH oxidase blockade. Cell therapy of normal or treated DOCA EPCs, but not untreated DOCA EPCs, significantly increased capillary density and blood perfusion in ischemic hindlimbs of DOCA-salt rats. p53 and Bax/Bcl-2 ratios were increased in EPCs of DOCA-salt rats, which were reversed by ETA antagonist or NADPH oxidase inhibitor or superoxide scavenger (PEG-SOD). Finally, in ETB-deficient rats, plasma ET-1 was elevated and EPC number and telomerase activity were diminished. These results demonstrate, for the first time, that ET-1 contributes to EPC reduction and dysfunction via an ETA/NADPH oxidase pathway-induced oxidative stress in salt-sensitive hypertension. PMID:22431579

  3. Critical role of renal dipeptidyl peptidase-4 in ameliorating kidney injury induced by saxagliptin in Dahl salt-sensitive hypertensive rats.

    PubMed

    Sakai, Mariko; Uchii, Masako; Myojo, Kensuke; Kitayama, Tetsuya; Kunori, Shunji

    2015-08-15

    Saxagliptin, a potent dipeptidyl peptidase-4 (DPP-4) inhibitor, is currently used to treat type 2 diabetes mellitus, and it has been reported to exhibit a slower rate of dissociation from DPP-4 compared with another DPP-4 inhibitor, sitagliptin. In this study, we compared the effects of saxagliptin and sitagliptin on hypertension-related renal injury and the plasma and renal DPP-4 activity levels in Dahl salt-sensitive hypertensive (Dahl-S) rats. The high-salt diet (8% NaCl) significantly increased the blood pressure and quantity of urinary albumin excretion and induced renal glomerular injury in the Dahl-S rats. Treatment with saxagliptin (14mg/kg/day via drinking water) for 4 weeks significantly suppressed the increase in urinary albumin excretion and tended to ameliorate glomerular injury without altering the blood glucose levels and systolic blood pressure. On the other hand, the administration of sitagliptin (140mg/kg/day via drinking water) did not affect urinary albumin excretion and glomerular injury in the Dahl-S rats. Meanwhile, the high-salt diet increased the renal DPP-4 activity but did not affect the plasma DPP-4 activity in the Dahl-S rats. Both saxagliptin and sitagliptin suppressed the plasma DPP-4 activity by 95% or more. Although the renal DPP-4 activity was also inhibited by both drugs, the inhibitory effect of saxagliptin was more potent than that of sitagliptin. These results indicate that saxagliptin has a potent renoprotective effect in the Dahl-S rats, independent of its glucose-lowering actions. The inhibition of the renal DPP-4 activity induced by saxagliptin may contribute to ameliorating renal injury in hypertension-related renal injury. PMID:25936515

  4. Renal denervation attenuates NADPH oxidase-mediated oxidative stress and hypertension in rats with hydronephrosis.

    PubMed

    Peleli, Maria; Al-Mashhadi, Ammar; Yang, Ting; Larsson, Erik; Wåhlin, Nils; Jensen, Boye L; G Persson, A Erik; Carlström, Mattias

    2016-01-01

    Hydronephrosis is associated with the development of salt-sensitive hypertension. Studies have suggested that increased sympathetic nerve activity and oxidative stress play important roles in hypertension and the modulation of salt sensitivity. The present study primarily aimed to examine the role of renal sympathetic nerve activity in the development of hypertension in rats with hydronephrosis. In addition, we aimed to investigate if NADPH oxidase (NOX) function could be affected by renal denervation. Partial unilateral ureteral obstruction (PUUO) was created in 3-wk-old rats to induce hydronephrosis. Sham surgery or renal denervation was performed at the same time. Blood pressure was measured during normal, high-, and low-salt diets. The renal excretion pattern, NOX activity, and expression as well as components of the renin-angiotensin-aldosterone system were characterized after treatment with the normal salt diet. On the normal salt diet, rats in the PUUO group had elevated blood pressure compared with control rats (115 ± 3 vs. 87 ± 1 mmHg, P < 0.05) and displayed increased urine production and lower urine osmolality. The blood pressure change in response to salt loading (salt sensitivity) was more pronounced in the PUUO group compared with the control group (15 ± 2 vs. 5 ± 1 mmHg, P < 0.05). Renal denervation in PUUO rats attenuated both hypertension (97 ± 3 mmHg) and salt sensitivity (5 ± 1 mmHg, P < 0.05) and normalized the renal excretion pattern, whereas the degree of renal fibrosis and inflammation was not changed. NOX activity and expression as well as renin and ANG II type 1A receptor expression were increased in the renal cortex from PUUO rats and normalized by denervation. Plasma Na(+) and K(+) levels were elevated in PUUO rats and normalized after renal denervation. Finally, denervation in PUUO rats was also associated with reduced NOX expression, superoxide production, and fibrosis in the heart. In conclusion, renal denervation attenuates

  5. MATERNAL DIET DURING GESTATION AND LACTATION MODIFIES THE SEVERITY OF SALT-INDUCED HYPERTENSION AND RENAL INJURY IN DAHL SALT-SENSITIVE RATS

    PubMed Central

    Geurts, Aron M.; Mattson, David L.; Liu, Pengyuan; Cabacungan, Erwin; Skelton, Meredith M.; Kurth, Theresa M.; Yang, Chun; Endres, Bradley T.; Klotz, Jason; Liang, Mingyu; Cowley, Allen W.

    2014-01-01

    Environmental exposure of parents or early in life may affect disease development in adults. We found that hypertension and renal injury induced by a high-salt diet were substantially attenuated in Dahl SS/JrHsdMcwiCrl (SS/Crl) rats that had been maintained for many generations on the grain-based 5L2F diet compared to SS/JrHsdMcwi rats (SS/Mcw) maintained on the casein-based AIN-76A diet (mean arterial pressure 116±9 vs. 154±25 mmHg; urinary albumin excretion 23±12 vs. 170±80 mg/day). RNA-seq analysis of the renal outer medulla identified 129 and 82 genes responding to a high-salt diet uniquely in SS/Mcw and SS/Crl rats, respectively, along with minor genetic differences between the SS substrains. The 129 genes responding to salt in the SS/Mcw strain included numerous genes with homologs associated with hypertension, cardiovascular disease, or renal disease in human. To narrow the critical window of exposure, we performed embryo transfer experiments in which single-cell embryos from one colony (SS/Mcw or SS/Crl) were transferred to surrogate mothers from the other colony, with parents and surrogate mothers maintained on their respective original diet. All offspring were fed the AIN-76A diet after weaning. Salt-induced hypertension and renal injury were substantially exacerbated in rats developed from SS/Crl embryos transferred to SS/Mcw surrogate mothers. Conversely, salt-induced hypertension and renal injury were significantly attenuated in rats developed from SS/Mcw embryos transferred to SS/Crl surrogate mothers. Together, the data suggests that maternal diet during the gestational-lactational period has substantial effects on the development of salt-induced hypertension and renal injury in adult SS rats. PMID:25452472

  6. Maternal diet during gestation and lactation modifies the severity of salt-induced hypertension and renal injury in Dahl salt-sensitive rats.

    PubMed

    Geurts, Aron M; Mattson, David L; Liu, Pengyuan; Cabacungan, Erwin; Skelton, Meredith M; Kurth, Theresa M; Yang, Chun; Endres, Bradley T; Klotz, Jason; Liang, Mingyu; Cowley, Allen W

    2015-02-01

    Environmental exposure of parents or early in life may affect disease development in adults. We found that hypertension and renal injury induced by a high-salt diet were substantially attenuated in Dahl SS/JrHsdMcwiCrl (SS/Crl) rats that had been maintained for many generations on the grain-based 5L2F diet compared with SS/JrHsdMcwi rats (SS/Mcw) maintained on the casein-based AIN-76A diet (mean arterial pressure, 116±9 versus 154±25 mm Hg; urinary albumin excretion, 23±12 versus 170±80 mg/d). RNAseq analysis of the renal outer medulla identified 129 and 82 genes responding to a high-salt diet uniquely in SS/Mcw and SS/Crl rats, respectively, along with minor genetic differences between the SS substrains. The 129 genes responding to salt in the SS/Mcw strain included numerous genes with homologs associated with hypertension, cardiovascular disease, or renal disease in human. To narrow the critical window of exposure, we performed embryo-transfer experiments in which single-cell embryos from 1 colony (SS/Mcw or SS/Crl) were transferred to surrogate mothers from the other colony, with parents and surrogate mothers maintained on their respective original diet. All offspring were fed the AIN-76A diet after weaning. Salt-induced hypertension and renal injury were substantially exacerbated in rats developed from SS/Crl embryos transferred to SS/Mcw surrogate mothers. Conversely, salt-induced hypertension and renal injury were significantly attenuated in rats developed from SS/Mcw embryos transferred to SS/Crl surrogate mothers. Together, the data suggest that maternal diet during the gestational-lactational period has substantial effects on the development of salt-induced hypertension and renal injury in adult SS rats. PMID:25452472

  7. High-intensity interval training attenuates endothelial dysfunction in a Dahl salt-sensitive rat model of heart failure with preserved ejection fraction.

    PubMed

    Adams, Volker; Alves, Marcia; Fischer, Tina; Rolim, Natale; Werner, Sarah; Schütt, Nicole; Bowen, T Scott; Linke, Axel; Schuler, Gerhard; Wisloff, Ulrik

    2015-09-15

    Heart failure patients with preserved left ventricular ejection fraction (HFpEF) have endothelial dysfunction, but the underlying molecular mechanisms remain unknown. In addition, whether exercise training improves endothelial function in HFpEF is still controversial. The present study therefore aimed to determine the functional and molecular alterations in the endothelium associated with HFpEF, while further assessing the effects of high-intensity interval training (HIT). Female Dahl salt-sensitive rats were randomized for 28 wk into the following groups: 1) control: fed 0.3% NaCl; 2) HFpEF: fed 8% NaCl; and 3) HFpEF + HIT: animals fed 8% NaCl and HIT treadmill exercise. Echocardiography and invasive hemodynamic measurements were used to assess diastolic dysfunction. Endothelial function of the aorta was measured in vitro. Expression of endothelial nitric oxide synthase (eNOS), nicotinamide adenine dinucleotide phosphate-oxidase [NAD(P)H oxidase], and advanced glycation end product (AGE)-modified proteins were quantified by Western blot, and zymography quantified matrix metalloproteinase (MMP) activity. In this model of HFpEF, endothelium-dependent and -independent vasodilation was impaired. However, this was prevented by HIT. In HFpEF protein expression of eNOS was reduced by 47%, but MMP-2 and MMP-9 activity was elevated by 186 and 68%. The expression of AGE-modified proteins was increased by 106%. All of these changes were prevented by HIT. Endothelial function was impaired in this model of HFpEF, which was associated with reduced expression of eNOS, increased MMP activity, and increased AGE-modified proteins. HIT was able to attenuate both these functional and molecular alterations. These findings therefore suggest HFpEF induces endothelial dysfunction, but this is reversible by HIT. PMID:26229002

  8. Role of the monocyte chemoattractant protein-1/C-C chemokine receptor 2 signaling pathway in transient receptor potential vanilloid type 1 ablation-induced renal injury in salt-sensitive hypertension.

    PubMed

    Wang, Youping; Zhu, Mingjun; Xu, Hui; Cui, Lin; Liu, Weihong; Wang, Xiaoxiao; Shen, Si; Wang, Donna H

    2015-09-01

    Our recent studies indicate that the transient receptor potential vanilloid type 1 (TRPV1) channel may act as a potential regulator of monocyte/macrophage recruitment to reduce renal injury in salt-sensitive hypertension. This study tests the hypothesis that deletion of TRPV1 exaggerates salt-sensitive hypertension-induced renal injury due to enhanced inflammatory responses via monocyte chemoattractant protein-1 (MCP-1)/C-C chemokine receptor 2 (CCR2)-dependent pathways. Wild type (WT) and TRPV1-null mutant (TRPV1(-/-)) mice were subjected to uninephrectomy and deoxycorticosterone acetate (DOCA)-salt treatment for four weeks with or without the selective CCR2 antagonist, RS504393. DOCA-salt treatment increased systolic blood pressure (SBP) to the same degree in both strains, but increased urinary excretion of albumin and 8-isoprostane and decreased creatinine clearance with greater magnitude in TRPV1(-/-) mice compared to WT mice. DOCA-salt treatment also caused renal glomerulosclerosis, tubulointerstitial injury, collagen deposition, monocyte/macrophage infiltration, proinflammatory cytokine and chemokine production, and NF-κB activation in greater degree in TRPV1(-/-) mice compared to WT mice. Blockade of the CCR2 with RS504393 (4 mg/kg/day) had no effect on SBP in DOCA-salt-treated WT or TRPV1(-/-) mice compared to their respective controls. However, treatment with RS504393 ameliorated renal dysfunction and morphological damage, and prevented the increase in monocyte/macrophage infiltration, cytokine/chemokine production, and NF-κB activity in both DOCA-salt hypertensive strains with a greater effect in DOCA-salt-treated TRPV1(-/-) mice compared to DOCA-salt-treated WT mice. No differences in CCR2 protein expression in kidney were found between DOCA-salt-treated WT and TRPV1(-/-) mice with or without RS504393 treatment. Our studies for the first time indicate that deletion of TRPV1 aggravated renal injury in salt-sensitive hypertension via enhancing MCP-1

  9. Plasma 24,25-dihydroxyvitamin D concentration of Dahl salt-sensitive rats decreases during high salt intake

    NASA Technical Reports Server (NTRS)

    Thierry-Palmer, Myrtle; Tewolde, Teclemicael K.; Forte, Camille; Wang, Min; Bayorh, Mohamed A.; Emmett, Nerimiah L.; White, Jolanda; Griffin, Keri

    2002-01-01

    Dahl salt-sensitive rats, but not salt-resistant rats, develop hypertension in response to high salt intake. We have previously shown an inverse relationship between plasma 25-hydroxyvitamin D (25-OHD) concentration and blood pressure of Dahl salt-sensitive rats during high salt intake. In this study, we report on the relationship between high salt intake and plasma 24,25-dihydroxyvitamin D (24,25-(OH)(2)D) concentration of Dahl salt-sensitive and salt-resistant rats. Rats were fed a high salt diet (8%) and sacrificed at day 2, 7, 14, 21, and 28. Plasma 24,25-(OH)(2)D concentrations of salt-sensitive rats were reduced to 50% of that at baseline at day 2-when blood pressure and plasma 25-OHD concentration were unchanged, but 25-OHD content in the kidney was 81% of that at baseline. Plasma 24,25-(OH)(2)D concentration was reduced further to 10% of that at baseline from day 7 to 14 of high salt intake, a reduction that was prevented in rats switched to a low salt (0.3%) diet at day 7. Exogenous 24,25-dihydroxycholecalciferol (24,25-(OH)(2)D(3)), administered at a level that increased plasma 24,25-(OH)(2)D concentration to five times normal, did not attenuate the salt-induced hypertension of salt-sensitive rats. Plasma 24,25-(OH)(2)D concentration of salt-resistant rats was gradually reduced to 50% of that at baseline at day 14 and returned to baseline value at day 28 of high salt intake. We conclude that the decrease in plasma 24,25-(OH)(2)D concentration in salt-sensitive rats during high salt intake is caused by decreased 25-OHD content in the kidney and also by another unidentified mechanism.

  10. Novel genetic variations associated with salt sensitivity in the Korean population.

    PubMed

    Rhee, Moo-Yong; Yang, Soo Jin; Oh, Sang Woo; Park, Yongsoon; Kim, Cho-il; Park, Hye-Kyung; Park, Sung Woo; Park, Cheol-Young

    2011-05-01

    Salt sensitivity is a risk factor for cardiovascular morbidity and mortality. To date, only a few genetic variations have been identified as being associated with salt sensitivity. This study aimed to estimate the prevalence of salt sensitivity in the Korean population and to identify genetic variants affecting its development. A total of 101 Korean participants consumed a low-salt diet for 7 days followed by a high-salt diet for 7 additional days. Salt sensitivity was determined by noting any significant elevation in the 24-h mean arterial blood pressure. To determine genetic variants affecting salt sensitivity, 36 single-nucleotide polymorphisms (SNPs) that were previously reported to be associated with hypertension were tested for any associations with salt sensitivity. Of the 101 subjects, 28 (27.7%) were determined to have salt sensitivity. Out of the 36 SNPs tested, four were significantly associated with salt sensitivity after adjusting for confounding factors: rs2681472 in ATPase, Ca(++) transporting, plasma membrane 1 (ATP2B1), rs7961152 in branched chain aminotransferase 1 (BCAT1), rs16998073 in fibroblast growth factor 5 (FGF5) and rs2398162 in LOC100132798. For rs3754777 in serine threonine kinase 39 (STK39) and rs1937506, associations with salt sensitivity were observed before adjusting for confounding factors. Haplotype analysis revealed that the A-C haplotype of rs3754777-rs6749447 in STK39 was more frequent in the salt-sensitive group compared with the salt-resistant group, and was associated with salt sensitivity. This study estimates the prevalence of salt sensitivity in the Korean population and demonstrates a novel association between salt sensitivity and the ATP2B1, BCAT1, FGF5, LOC100132798 and STK39 genetic variations. PMID:21228780

  11. Salt sensitivity: a review with a focus on non-Hispanic blacks and Hispanics

    PubMed Central

    Richardson, Safiya I.; Freedman, Barry I.; Ellison, David H.; Rodriguez, Carlos J.

    2015-01-01

    The purpose of this review is to summarize the available information regarding salt sensitivity particularly as it relates to non-Hispanic blacks and Hispanics and to clarify possible etiologies, especially those that might shed light on potential treatment options. In non-Hispanic blacks, there is evidence that endothelial dysfunction, reduced potassium intake, decreased urinary kallikrein excretion, upregulation of sodium channel activity, dysfunction in atrial natriuretic peptide (ANP) production, and APOL1 gene nephropathy risk variants may cause or contribute to salt sensitivity. Supported treatment avenues include diets high in potassium and soybean protein, the components of which stimulate nitric oxide production. Racial heterogeneity complicates the study of salt sensitivity in Hispanic populations. Caribbean Hispanics, who have a higher proportion of African ancestry, may respond to commonly prescribed anti-hypertensive agents in a way that is characteristic of non-Hispanic black hypertensives. The low-renin hypertensive phenotype commonly seen in non-Hispanic blacks has been linked to salt sensitivity and may indicate an increased risk for salt sensitivity in a portion of the Hispanic population. In conclusion, increased morbidity and mortality associated with salt sensitivity mandates further studies evaluating the efficacy of tailored dietary and pharmacologic treatment in non-Hispanic blacks and determining the prevalence of low renin hypertension and salt sensitivity within the various subgroups of Hispanic Americans. PMID:23428408

  12. Overexpression of VEGF-C attenuates chronic high salt intake-induced left ventricular maladaptive remodeling in spontaneously hypertensive rats.

    PubMed

    Yang, Guo-Hong; Zhou, Xin; Ji, Wen-Jie; Zeng, Shan; Dong, Yan; Tian, Lu; Bi, Ying; Guo, Zhao-Zeng; Gao, Fei; Chen, Hong; Jiang, Tie-Min; Li, Yu-Ming

    2014-02-15

    Recent studies have shown that the tonicity-responsive enhancer binding protein (TonEBP)/vascular endothelial growth factor-C (VEGF-C) signaling pathway-induced lymphangiogenesis provides a buffering mechanism for high salt (HS) intake-induced elevation of blood pressure (BP). Moreover, blocking of TonEBP/VEGF-C signaling by mononuclear phagocyte depletion can induce salt-sensitive hypertension in rats. We hypothesized that HS intake could have an impact on cardiac lymphangiogenesis, and regulation of VEGF-C bioactivity, which is largely through the main receptor for VEGFR-3, may modulate HS intake-induced left ventricular remodeling. We demonstrated upregulation of TonEBP, increased macrophage infiltration, and enhanced lymphangiogenesis in the left ventricles of spontaneously hypertensive rats (SHR) that were fed a HS diet (8.0% NaCl). Then, retrovirus vectors capable of overexpression (ΔNΔC/VEGF-C/Cys152Ser, used for overexpressing VEGF-C) and blocking (VEGFR-3-Rg, used for trapping of bioactive VEGF-C) of VEGF-C and control vector (pLPCX) were intravenously administered to SHR from week 9 of a 12-wk HS loading period. At the end of the HS challenge, overexpression of VEGF-C led to enhanced cardiac lymphangiogenesis, decreased myocardial fibrosis, and macrophage infiltration, preserved left ventricular functions, as well as decreased blood pressure level compared with the HS group and the control vector-treated HS group. In contrast, systemic blocking of VEGF-C was associated with elevation of blood pressure level and an exacerbation of hypertensive left ventricular remodeling, as indicated by increased fibrosis and macrophage infiltration, and diminished lymphangiogenesis. Hence, our findings highlight that VEGF-C/VEGFR-3 is a promising therapeutic target to attenuate hypertensive left ventricular remodeling induced by HS intake, presumably via blood pressure-dependent and -independent mechanisms. PMID:24337460

  13. Mycophenolate mofetil attenuates pulmonary arterial hypertension in rats

    SciTech Connect

    Suzuki, Chihiro; Takahashi, Masafumi . E-mail: masafumi@sch.md.shinshu-u.ac.jp; Morimoto, Hajime; Izawa, Atsushi; Ise, Hirohiko; Hongo, Minoru; Hoshikawa, Yasushi; Ito, Takayuki; Miyashita, Hiroshi; Kobayashi, Eiji; Shimada, Kazuyuki; Ikeda, Uichi

    2006-10-20

    Pulmonary arterial hypertension (PAH) is characterized by abnormal proliferation of smooth muscle cells (SMCs), leading to occlusion of pulmonary arterioles, right ventricular (RV) hypertrophy, and death. We investigated whether mycophenolate mofetil (MMF), a potent immunosuppresssant, prevents the development of monocrotaline (MCT)-induced PAH in rats. MMF effectively decreased RV systolic pressure and RV hypertrophy, and reduced the medial thickness of pulmonary arteries. MMF significantly inhibited the number of proliferating cell nuclear antigen (PCNA)-positive cells, infiltration of macrophages, and expression of P-selectin and interleukin-6 on the endothelium of pulmonary arteries. The infiltration of T cells and mast cells was not affected by MMF. In vitro experiments revealed that mycophenolic acid (MPA), an active metabolite of MMF, dose-dependently inhibited proliferation of human pulmonary arterial SMCs. MMF attenuated the development of PAH through its anti-inflammatory and anti-proliferative properties. These findings provide new insight into the potential role of immunosuppressants in the treatment of PAH.

  14. MURC deficiency in smooth muscle attenuates pulmonary hypertension

    PubMed Central

    Nakanishi, Naohiko; Ogata, Takehiro; Naito, Daisuke; Miyagawa, Kotaro; Taniguchi, Takuya; Hamaoka, Tetsuro; Maruyama, Naoki; Kasahara, Takeru; Nishi, Masahiro; Matoba, Satoaki; Ueyama, Tomomi

    2016-01-01

    Emerging evidence suggests that caveolin-1 (Cav1) is associated with pulmonary arterial hypertension. MURC (also called Cavin-4) is a member of the cavin family, which regulates caveolar formation and functions together with caveolins. Here, we show that hypoxia increased Murc mRNA expression in the mouse lung, and that Murc-null mice exhibited attenuation of hypoxia-induced pulmonary hypertension (PH) accompanied by reduced ROCK activity in the lung. Conditional knockout mice lacking Murc in smooth muscle also resist hypoxia-induced PH. MURC regulates the proliferation and migration of pulmonary artery smooth muscle cells (PASMCs) through Rho/ROCK signalling. Cav1 suppresses RhoA activity in PASMCs, which is reversed by MURC. MURC binds to Cav1 and inhibits the association of Cav1 with the active form of Gα13, resulting in the facilitated association of the active form of Gα13 with p115RhoGEF. These results reveal that MURC has a function in the development of PH through modulating Rho/ROCK signalling. PMID:27546070

  15. The blood pressure-salt sensitivity paradigm: pathophysiologically sound yet of no practical value.

    PubMed

    Galletti, Ferruccio; Strazzullo, Pasquale

    2016-09-01

    Sodium plays an important pathophysiological role in blood pressure (BP) values and in the development of hypertension, and epidemiological studies such as the Intersalt Study have shown that the increase in BP occurring with age is determined by salt intake. Recently, a meta-analysis of 13 prospective studies has also shown the close relationship between excess sodium intake and higher risk of stroke and total cardiovascular events. However, the BP response to changing salt intake displayed a marked variability, as first suggested by Kawasaki et al. (The effect of high-sodium and low-sodium intakes on blood pressure and other related variables in human subjects with idiopathic hypertension. Am J Med 1978; 64: 193-198) and later by Weinberger et al. (Definitions and characteristics of sodium sensitivity and blood pressure resistance. Hypertension 1986; 8: II127-II134), who recognized the heterogeneity of the BP response to salt and developed the concept of salt sensitivity. We have a large body of evidence in favour of a major role of metabolic and neuro-hormonal factors in determining BP salt sensitivity in association with the effect of genetic variation. There is evidence that salt sensitivity influences the development of organ damage, even independently-at least in part-of BP levels and the occurrence of hypertension. In addition, several observational studies indicate that salt sensitivity is clearly associated with a higher rate of cardiovascular events and mortality, independently of BP levels and hypertension. A cluster of factors with well-known atherogenic potential such as hyperinsulinaemia, dyslipidaemia and microalbuminuria-all known to be prevalent in salt-sensitive hypertension-might at least partially explain the increased cardiovascular risk observed in salt sensitive individuals. The gold standard for the evaluation of BP salt sensitivity is the BP response to a moderate reduction of salt intake for several weeks; nevertheless, these protocols

  16. Nifedipine attenuation of abdominal aortic aneurysm in hypertensive and non-hypertensive mice: Mechanisms and implications.

    PubMed

    Miao, Xiao Niu; Siu, Kin Lung; Cai, Hua

    2015-10-01

    Rupture of abdominal aortic aneurysm (AAA) is a lethal event. No oral medicine has been available to prevent or treat AAA. We have recently identified a novel mechanism of eNOS uncoupling by which AAA develops, in angiotensin II (Ang II) infused hyperphenylalaninemia 1 (hph-1) mice. Using this unique model we investigated effects on AAA formation of the L-type calcium channel blocker nifedipine, in view of the unclear relationship between hypertension and AAA, and unclear mechanisms of aneurysm protective effects of some blood pressure lowering drugs. Six-month old hph-1 mice were infused with Ang II (0.7 mg/kg/day) for 2 weeks, and fed nifedipine chow at two different doses (5 and 20 mg/kg/day). While the high dose of nifedipine reduced blood pressure, the lower dose had no effect. Interestingly, the incidence rate of AAA dropped from 71% to 7 and 12.5% for low and high dose nifedipine, respectively. Expansion of abdominal aorta, determined by ultrasound imaging, was abolished by both doses of nifedipine, which recoupled eNOS completely to improve NO bioavailability. Both also abrogated aortic superoxide production. Of note, Ang II activation of NADPH oxidase in vascular smooth muscle cells and endothelial cells, known to uncouple eNOS, was also attenuated by nifedipine. Although low dose was a sub-pressor while the high dose reduced blood pressure via inhibition of calcium channels, both doses were highly effective in preventing AAA by preserving eNOS coupling activity to eliminate sustained oxidative stress from uncoupled eNOS. These data demonstrate that oral treatment of nifedipine is highly effective in preserving eNOS function to attenuate AAA formation. Nifedipine may be used for AAA prevention either at low dose in AAA risk group, or at high dose in patients with co-existing hypertension. PMID:26254182

  17. A blueberry enriched diet attenuates nephropathy in a rat model of hypertension via reduction in oxidative stress

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Objective: To assess renoprotective effects of a blueberry-enriched diet in a rat model of hypertension. Background: Oxidative stress (OS) appears to be involved in the development of hypertension and related renal injury. Pharmacological antioxidants can attenuate hypertension and hypertension-indu...

  18. Comparative effects of valsartan in combination with cilnidipine or amlodipine on cardiac remodeling and diastolic dysfunction in Dahl salt-sensitive rats.

    PubMed

    Nagasawa, Kai; Takahashi, Keiji; Matsuura, Natsumi; Takatsu, Miwa; Hattori, Takuya; Watanabe, Shogo; Harada, Eri; Niinuma, Kazumi; Murohara, Toyoaki; Nagata, Kohzo

    2015-01-01

    Angiotensin receptor blockers (ARBs) are often supplemented with calcium channel blockers (CCBs) for treatment of hypertension. We recently showed that the L/N-type CCB cilnidipine has superior cardioprotective effects compared with the L-type CCB amlodipine in Dahl salt-sensitive (DS) rats. We have now compared the effects of the ARB valsartan combined with cilnidipine or amlodipine on cardiac pathophysiology in DS rats. DS rats fed a high-salt diet from 6 weeks of age were treated with vehicle, valsartan alone (10 mg kg(-1) per day), or valsartan combined with either cilnidipine (1 mg kg(-1) per day) or amlodipine (1 mg kg(-1) per day) from 7 to 11 weeks. The salt-induced increase in systolic blood pressure apparent in the vehicle group was attenuated similarly in the three drug treatment groups. Valsartan-cilnidipine attenuated left ventricular (LV) fibrosis and diastolic dysfunction as well as cardiac oxidative stress and inflammation to a greater extent than did valsartan alone or valsartan-amlodipine. In addition, the increases in urinary excretion of dopamine and epinephrine as well as in cardiac renin-angiotensin-aldosterone-system (RAAS) gene expression apparent in vehicle-treated rats were attenuated to a greater extent by valsartan-cilnidipine than by the other two treatments. Valsartan-cilnidipine thus attenuated LV remodeling and diastolic dysfunction more effectively than did valsartan or valsartan-amlodipine in rats with salt-sensitive hypertension, and this superior cardioprotective action of valsartan-cilnidipine compared with valsartan-amlodipine is likely attributable, at least in part, to the greater antioxidant and antiinflammatory effects associated with both greater inhibition of cardiac RAAS gene expression and N-type calcium channel blockade. PMID:25209105

  19. Soluble Guanylate Cyclase Stimulation Prevents Fibrotic Tissue Remodeling and Improves Survival in Salt-Sensitive Dahl Rats

    PubMed Central

    Geschka, Sandra; Kretschmer, Axel; Sharkovska, Yuliya; Evgenov, Oleg V.; Lawrenz, Bettina; Hucke, Andreas; Hocher, Berthold; Stasch, Johannes-Peter

    2011-01-01

    Background A direct pharmacological stimulation of soluble guanylate cyclase (sGC) is an emerging therapeutic approach to the management of various cardiovascular disorders associated with endothelial dysfunction. Novel sGC stimulators, including riociguat (BAY 63-2521), have a dual mode of action: They sensitize sGC to endogenously produced nitric oxide (NO) and also directly stimulate sGC independently of NO. Little is known about their effects on tissue remodeling and degeneration and survival in experimental malignant hypertension. Methods and Results Mortality, hemodynamics and biomarkers of tissue remodeling and degeneration were assessed in Dahl salt-sensitive rats maintained on a high salt diet and treated with riociguat (3 or 10 mg/kg/d) for 14 weeks. Riociguat markedly attenuated systemic hypertension, improved systolic heart function and increased survival from 33% to 85%. Histological examination of the heart and kidneys revealed that riociguat significantly ameliorated fibrotic tissue remodeling and degeneration. Correspondingly, mRNA expression of the pro-fibrotic biomarkers osteopontin (OPN), tissue inhibitor of matrix metalloproteinase-1 (TIMP-1) and plasminogen activator inhibitor-1 (PAI-1) in the myocardium and the renal cortex was attenuated by riociguat. In addition, riociguat reduced plasma and urinary levels of OPN, TIMP-1, and PAI-1. Conclusions Stimulation of sGC by riociguat markedly improves survival and attenuates systemic hypertension and systolic dysfunction, as well as fibrotic tissue remodeling in the myocardium and the renal cortex in a rodent model of pressure and volume overload. These findings suggest a therapeutic potential of sGC stimulators in diseases associated with impaired cardiovascular and renal functions. PMID:21789188

  20. Grating formation in diazo salt (sensitized) gelatin.

    PubMed

    Gladden, J W

    1980-05-01

    Diazo (sensitized) gelatins are photosensitive recording materials that, unlike dichromated gelatin, have a long shelf life. Because of their stability, the diazo emulsions have replaced the dichromated colloids used in the photolithographic field and enabled commercialization of presensitized printing plates. We have produced plane wave gratings with peak efficiencies near 67% at an exposure of 625 mJ/cm(2) and a recording wavelength of 488.0 nm in one diazo recording material. Called diazo salt (sensitized) gelatin, the photosensitive material produces gratings in gelatin by a complex process that we found not to be a function of exposure. The methods used are described. PMID:20221070

  1. Polydatin Attenuates Hypoxic Pulmonary Hypertension and Reverses Remodeling through Protein Kinase C Mechanisms

    PubMed Central

    Miao, Qing; Shi, Xiao-Peng; Ye, Ming-Xiang; Zhang, Jin; Miao, Shan; Wang, Si-Wang; Li, Bo; Jiang, Xiu-Xiu; Zhang, Song; Hu, Nan; Li, Juan; Zhang, Jian

    2012-01-01

    Hypoxic pulmonary hypertension is a life-threatening emergency if untreated. Consistent pulmonary hypertension also leads to arteries and ventricular remodeling. The clinical therapeutic strategy for pulmonary hypertension and the corresponding remodeling mainly interacts with NO, angiotensin II (Ang II) and elevated endothelin (ET) targets. In the present study, we evaluated the effects of polydatin on hypoxia-induced pulmonary hypertension. It was observed that polydatin attenuated hypoxic pulmonary hypertension, reversed remodeling, and regulated NO, Ang II, ET contents in the serum and lung samples. However, forced activation of PKC signaling by its selective activator thymeleatoxin (THX) could abate the effects of polydatain. These results suggest that polydatin might be a promising candidate for hypoxic pulmonary treatment through interaction with PKC mechanisms. PMID:22837726

  2. Sodium nitrite therapy attenuates hypertensive effects of HBOC-201 via nitrite reduction

    PubMed Central

    Rodriguez, Cilina; Vitturi, Dario A.; He, Jin; Vandromme, Marianne; Brandon, Angela; Hutchings, Anne; Rue, Loring W.; Kerby, Jeffrey D; Patel, Rakesh P.

    2009-01-01

    Synopsis Hypertension secondary to scavenging of nitric oxide (NO) remains a limitation in the use hemoglobin based oxygen carriers (HBOCs). Recent studies suggest that nitrite reduction to NO by deoxyhemoglobin supports NO-signaling. Herein, we tested whether nitrite would attenuate HBOC-mediated hypertension using HBOC-201 (Biopure), a bovine cross-linked, low oxygen affinity hemoglobin. Similar to unmodified hemoglobin, deoxygenated HBOC-201 reduced nitrite to NO with rates directly proportional to the extent of deoxygenation. The functional importance of HBOC-201 dependent nitrite reduction was demonstrated using isolated aortic rings and a murine model of trauma, hemorrhage and resuscitation. In the former, HBOC-201 inhibited NO-donor and nitrite-dependent vasodilation when oxygenated. However, deoxygenated HBOC-201 failed to affect nitrite dependent vasodilation but still inhibited NO-donor dependent vasodilation consistent with a model in which nitrite-reduction by deoxyHBOC-201 counters NO-scavenging. Finally, resuscitation using HBOC-201 after trauma and hemorrhage, resulted in mild hypertension (~5-10mmHg). Administration of a single bolus nitrite (30-100nmol) at the onset of HBOC-201 resuscitation prevented hypertension. Nitrite had no effect on mean arterial pressure during resuscitation with lactated Ringers suggesting a role for nitrite-HBOC reactions in attenuating HBOC-mediated hypertension. Taken together these data support the concept that nitrite can be used as an adjunct therapy to prevent HBOC-dependent hypertension. PMID:19555351

  3. Salt sensitivity of blood pressure is associated with polymorphisms in the sodium-bicarbonate cotransporter.

    PubMed

    Carey, Robert M; Schoeffel, Cynthia D; Gildea, John J; Jones, John E; McGrath, Helen E; Gordon, Lindsay N; Park, Min Jeong; Sobota, Rafal S; Underwood, Patricia C; Williams, Jonathan; Sun, Bei; Raby, Benjamin; Lasky-Su, Jessica; Hopkins, Paul N; Adler, Gail K; Williams, Scott M; Jose, Pedro A; Felder, Robin A

    2012-11-01

    Previous studies have demonstrated that single nucleotide polymorphisms (SNPs) of the sodium-bicarbonate co-transporter gene (SLC4A5) are associated with hypertension. We tested the hypothesis that SNPs in SLC4A5 are associated with salt sensitivity of blood pressure in 185 whites consuming an isocaloric constant diet with a randomized order of 7 days of low Na(+) (10 mmol/d) and 7 days of high Na(+) (300 mmol/d) intake. Salt sensitivity was defined as a ≥ 7-mm Hg increase in mean arterial pressure during a randomized transition between high and low Na(+) diet. A total of 35 polymorphisms in 17 candidate genes were assayed, 25 of which were tested for association. Association analyses with salt sensitivity revealed 3 variants that associated with salt sensitivity, 2 in SLC4A5 (P<0.001) and 1 in GRK4 (P=0.020). Of these, 2 SNPs in SLC4A5 (rs7571842 and rs10177833) demonstrated highly significant results and large effects sizes, using logistic regression. These 2 SNPs had P values of 1.0 × 10(-4) and 3.1 × 10(-4) with odds ratios of 0.221 and 0.221 in unadjusted regression models, respectively, with the G allele at both sites conferring protection. These SNPs remained significant after adjusting for body mass index and age (P=8.9 × 10(-5) and 2.6 × 10(-4) and odds ratios 0.210 and 0.286, respectively). Furthermore, the association of these SNPs with salt sensitivity was replicated in a second hypertensive population. Meta-analysis demonstrated significant associations of both SNPs with salt sensitivity (rs7571842 [P=1.2 × 10(-5)]; rs1017783 [P=1.1 × 10(-4)]). In conclusion, SLC4A5 variants are strongly associated with salt sensitivity of blood pressure in 2 separate white populations. PMID:22987918

  4. Vascular glycocalyx sodium store – determinant of salt sensitivity?

    PubMed

    Oberleithner, Hans; Wilhelmi, Marianne

    2015-01-01

    Smart mechanisms allow frictionless slipping of rather rigid erythrocytes (red blood cells, RBC) through narrow blood vessels. Nature solved this problem in an elegant way coating the moving object (RBC) and the tunnel wall (endothelium) by negative charges (glycocalyx). As long as these surfaces are intact, repulsive forces create a 'security zone' that keeps the respective surfaces separated from each other. However, damage of either one of these surfaces causes loss of negative charges, allowing an unfavorable physical interaction between the RBC and the endothelium. It has been recently shown that any alteration of the endothelial glycocalyx leaves nasty footprints on the RBC glycocalyx. In this scenario, sodium ions hold a prominent role. Plasma sodium is stored in the glycocalyx partially neutralizing the negative surface charges. A 'good' glycocalyx has a high sodium store capacity but still maintains sufficient surface negativity at normal plasma sodium. A 'bad' glycocalyx shows the opposite. This concept was used for the development of the so-called 'salt blood test' (SBT) that quantitatively measures RBC sodium store capacity of the glycocalyx and thus indirectly evaluates the quality of the inner vessel wall. In an initial step, the applicability of the SBT was tested in eight different medical facilities. The study shows that an increased salt sensitivity, as measured by the SBT, is more frequently found in individuals with a hypertensive history, despite antihypertensive medication. Taken together, preservation of the endothelial glycocalyx appears to be of utmost importance for maintaining a well-balanced function of the vascular system. PMID:25659848

  5. SALT SENSITIVITY IN RESPONSE TO RENAL INJURY REQUIRES RENAL ANGIOTENSIN-CONVERTING ENZYME

    PubMed Central

    Giani, Jorge F.; Bernstein, Kenneth E.; Janjulia, Tea; Han, Jiyang; Toblli, Jorge E.; Shen, Xiao Z.; Rodriguez-Iturbe, Bernardo; McDonough, Alicia A.; Gonzalez-Villalobos, Romer A.

    2015-01-01

    Recent evidence indicates that salt-sensitive hypertension can result from a subclinical injury that impairs the kidneys’ capacity to properly respond to a high salt diet. However, how this occurs is not well understood. Here, we showed that while previously salt resistant wild-type mice became salt-sensitive after the induction of renal injury with the nitric oxide synthase inhibitor Nω-Nitro-L-arginine methyl ester hydrochloride (L-NAME); mice lacking renal angiotensin-converting enzyme, exposed to the same insult, did not become hypertensive when faced with a sodium load. This is because the activity of renal angiotensin-converting enzyme plays a critical role in: 1) augmenting the local pool of angiotensin II and, 2) the establishment of the anti-natriuretic state via modulation of glomerular filtration rate and sodium tubular transport. Thus, this study demonstrates that the presence of renal angiotensin-converting enzyme plays a pivotal role in the development of salt sensitivity in response to renal injury. PMID:26150439

  6. Cinnamaldehyde Attenuates Cataractogenesis via Restoration of Hypertension and Oxidative Stress in Fructose-Fed Hypertensive rats

    PubMed Central

    Singh, Amrita; Khan, Samsroz Ahmad; Choudhary, Rajesh

    2016-01-01

    Objectives: Several studies have revealed that systemic hypertension is strongly associated with cataractogenesis. However, the pathophysiology and treatment is often unclear. In this study, we evaluated the anti-cataractogenic effect of cinnamaldehyde (CA), a natural organic compound, in rats with fructose-induced hypertension. Methods: The rats were divided into six groups. For six weeks, the normal group received a suspension of 0.5% carboxy methyl cellulose (10 mL/kg/day, p.o.) while five other groups received a 10% (w/v) fructose solution in their drinking water to induce hypertension. By the end of the third week hypertension had been induced in all the animals receiving fructose. From the beginning of the fourth week to the end of the sixth week, one of those five groups (control) continued to receive only 10% (w/v) fructose solution, one group (standard) received ramipril (1 mg/kg/day, p.o.) plus 10% (w/v) fructose solution, and three groups (experimental) received CA at doses of 20, 30, and 40 mg/kg/day p.o., plus 10% (w/v) fructose solution. Blood pressure was measured weekly using a non-invasive blood pressure apparatus. After six weeks, the animals were sacrificed, and the anti-cataractogenic effects on the eye lenses were evaluated. Results: Administration of fructose elevated both the systolic and the diastolic blood pressures, which were significantly reduced by CA at all dose levels. In the control group, a significant increase in the malonaldehyde (MDA) level and decreases in the total protein, Ca2+adenosine triphosphate (ATP)ase activity, glutathione peroxidase, catalase, superoxide dismutase and glutathione levels, as compared to the normal group, were observed. Administration of CA at all doses significantly restored the enzymatic, non-enzymatic, antioxidants, total protein, and Ca2+ATPase levels, but decreased the MDA level, as compared to the control group. Conclusion: The present study revealed that CA modulated the antioxidant parameters of

  7. Histone deacetylase inhibitor, CG200745, attenuates cardiac hypertrophy and fibrosis in DOCA-induced hypertensive rats

    PubMed Central

    Lee, Eunjo; Song, Min-ji; Lee, Hae-Ahm; Kang, Seol-Hee; Kim, Mina; Yang, Eun Kyoung; Lee, Do Young; Ro, Seonggu; Cho, Joong Myung

    2016-01-01

    CG200745 is a novel inhibitor of histone deacetylases (HDACs), initially developed for treatment of various hematological and solid cancers. Because it is water-soluble, it can be administered orally. We hypothesized that the HDAC inhibitor, CG200745, attenuates cardiac hypertrophy and fibrosis in deoxycorticosterone acetate (DOCA)-induced hypertensive rats. For establishment of hypertension, 40 mg/kg of DOCA was subcutaneously injected four times weekly into Sprague-Dawley rats. All the rats used in this study including those in the sham group had been unilaterally nephrectomized and allowed free access to drinking water containing 1% NaCl. Systolic blood pressure was measured by the tail-cuff method. Blood chemistry including sodium, potassium, glucose, triglyceride, and cholesterol levels was analyzed. Sections of the heart were visualized after trichrome and hematoxylin and eosin stain. The expression of hypertrophic genes such as atrial natriuretic peptide A (Nppa) and atrial natriuretic peptide B (Nppb) in addition to fibrotic genes such as Collagen-1, Collagen-3, connective tissue growth factor (Ctgf), and Fibronectin were measured by quantitative real-time PCR (qRT-PCR). Injection of DOCA increased systolic blood pressure, heart weight, and cardiac fibrosis, which was attenuated by CG200745. Neither DOCA nor CG200745 affected body weight, vascular contraction and relaxation responses, and blood chemistry. Injection of DOCA increased expression of both hypertrophic and fibrotic genes, which was abrogated by CG200745. These results indicate that CG200745 attenuates cardiac hypertrophy and fibrosis in DOCA-induced hypertensive rats. PMID:27610034

  8. Histone deacetylase inhibitor, CG200745, attenuates cardiac hypertrophy and fibrosis in DOCA-induced hypertensive rats.

    PubMed

    Lee, Eunjo; Song, Min-Ji; Lee, Hae-Ahm; Kang, Seol-Hee; Kim, Mina; Yang, Eun Kyoung; Lee, Do Young; Ro, Seonggu; Cho, Joong Myung; Kim, Inkyeom

    2016-09-01

    CG200745 is a novel inhibitor of histone deacetylases (HDACs), initially developed for treatment of various hematological and solid cancers. Because it is water-soluble, it can be administered orally. We hypothesized that the HDAC inhibitor, CG200745, attenuates cardiac hypertrophy and fibrosis in deoxycorticosterone acetate (DOCA)-induced hypertensive rats. For establishment of hypertension, 40 mg/kg of DOCA was subcutaneously injected four times weekly into Sprague-Dawley rats. All the rats used in this study including those in the sham group had been unilaterally nephrectomized and allowed free access to drinking water containing 1% NaCl. Systolic blood pressure was measured by the tail-cuff method. Blood chemistry including sodium, potassium, glucose, triglyceride, and cholesterol levels was analyzed. Sections of the heart were visualized after trichrome and hematoxylin and eosin stain. The expression of hypertrophic genes such as atrial natriuretic peptide A (Nppa) and atrial natriuretic peptide B (Nppb) in addition to fibrotic genes such as Collagen-1, Collagen-3, connective tissue growth factor (Ctgf), and Fibronectin were measured by quantitative real-time PCR (qRT-PCR). Injection of DOCA increased systolic blood pressure, heart weight, and cardiac fibrosis, which was attenuated by CG200745. Neither DOCA nor CG200745 affected body weight, vascular contraction and relaxation responses, and blood chemistry. Injection of DOCA increased expression of both hypertrophic and fibrotic genes, which was abrogated by CG200745. These results indicate that CG200745 attenuates cardiac hypertrophy and fibrosis in DOCA-induced hypertensive rats. PMID:27610034

  9. Chronic cathepsin inhibition by E-64 in Dahl salt-sensitive rats.

    PubMed

    Blass, Gregory; Levchenko, Vladislav; Ilatovskaya, Daria V; Staruschenko, Alexander

    2016-09-01

    Cysteine cathepsins are lysosomal enzymes expressed in the kidneys and other tissues, and are involved in the maturation and breakdown of cellular proteins. They have been shown to be integrally involved in the progression of many cardiovascular and renal diseases. The goal of this study was to determine the involvement of cysteine cathepsins in the development of salt-sensitive hypertension and associated kidney damage. In our experiments, Dahl salt-sensitive (SS) rats were fed an 8% high salt NaCl diet and intravenously infused with the irreversible cysteine cathepsin inhibitor E-64 (1 mg/day) or the vehicle (control). Both the control and E-64 infused groups developed significant hypertension and kidney damage, and no difference of the mean arterial pressure and the hypertension-associated albuminuria was observed between the groups. We next tested basal calcium levels in the podocytes of both control and infused groups using confocal calcium imaging. Basal calcium did not differ between the groups, indicative of the lack of a protective or aggravating influence by the cathepsin inhibition. The efficacy of E-64 was tested in Western blotting. Our findings corresponded to the previously reported, E-64 induced increase in cathepsin B and L abundance. We conclude that the inhibition of cysteine cathepsins by E-64 does not have any effects on the blood pressure development and kidney damage, at least under the studied conditions of this model of SS hypertension. PMID:27597769

  10. Chronic infusion of lisinopril into hypothalamic paraventricular nucleus modulates cytokines and attenuates oxidative stress in rostral ventrolateral medulla in hypertension

    SciTech Connect

    Li, Hong-Bao; Qin, Da-Nian; Ma, Le; Miao, Yu-Wang; Zhang, Dong-Mei; Lu, Yan; Song, Xin-Ai; Zhu, Guo-Qing; Kang, Yu-Ming

    2014-09-01

    The hypothalamic paraventricular nucleus (PVN) and rostral ventrolateral medulla (RVLM) play a critical role in the generation and maintenance of sympathetic nerve activity. The renin–angiotensin system (RAS) in the brain is involved in the pathogenesis of hypertension. This study was designed to determine whether inhibition of the angiotensin-converting enzyme (ACE) in the PVN modulates cytokines and attenuates oxidative stress (ROS) in the RVLM, and decreases the blood pressure and sympathetic activity in renovascular hypertensive rats. Renovascular hypertension was induced in male Sprague–Dawley rats by the two-kidney one-clip (2K1C) method. Renovascular hypertensive rats received bilateral PVN infusion with ACE inhibitor lisinopril (LSP, 10 μg/h) or vehicle via osmotic minipump for 4 weeks. Mean arterial pressure (MAP), renal sympathetic nerve activity (RSNA), and plasma proinflammatory cytokines (PICs) were significantly increased in renovascular hypertensive rats. The renovascular hypertensive rats also had higher levels of ACE in the PVN, and lower level of interleukin-10 (IL-10) in the RVLM. In addition, the levels of PICs, the chemokine MCP-1, the subunit of NAD(P)H oxidase (gp91{sup phox}) and ROS in the RVLM were increased in hypertensive rats. PVN treatment with LSP attenuated those changes occurring in renovascular hypertensive rats. Our findings suggest that the beneficial effects of ACE inhibition in the PVN in renovascular hypertension are partly due to modulation cytokines and attenuation oxidative stress in the RVLM. - Highlights: • Chronic ACE inhibition in PVN on renovascular hypertension was investigated. • 2K1C resulted in sympathoexcitation, increased plasma PICs and hypertension. • 2K1C rats had higher levels of cytokines and reactive oxygen species (ROS) in RVLM. • Chronic inhibiting PVN ACE attenuates cytokines and ROS in RVLM in hypertension.

  11. Heme biosynthesis modulation via δ-aminolevulinic acid administration attenuates chronic hypoxia-induced pulmonary hypertension

    PubMed Central

    Alhawaj, Raed; Patel, Dhara; Kelly, Melissa R.; Sun, Dong

    2015-01-01

    This study examines how heme biosynthesis modulation with δ-aminolevulinic acid (ALA) potentially functions to prevent 21-day hypoxia (10% oxygen)-induced pulmonary hypertension in mice and the effects of 24-h organoid culture with bovine pulmonary arteries (BPA) with the hypoxia and pulmonary hypertension mediator endothelin-1 (ET-1), with a focus on changes in superoxide and regulation of micro-RNA 204 (miR204) expression by src kinase phosphorylation of signal transducer and activator of transcription-3 (STAT3). The treatment of mice with ALA attenuated pulmonary hypertension (assessed through echo Doppler flow of the pulmonary valve, and direct measurements of right ventricular systolic pressure and right ventricular hypertrophy), increases in pulmonary arterial superoxide (detected by lucigenin), and decreases in lung miR204 and mitochondrial superoxide dismutase (SOD2) expression. ALA treatment of BPA attenuated ET-1-induced increases in mitochondrial superoxide (detected by MitoSox), STAT3 phosphorylation, and decreases in miR204 and SOD2 expression. Because ALA increases BPA protoporphyrin IX (a stimulator of guanylate cyclase) and cGMP-mediated protein kinase G (PKG) activity, the effects of the PKG activator 8-bromo-cGMP were examined and found to also attenuate the ET-1-induced increase in superoxide. ET-1 increased superoxide production and the detection of protoporphyrin IX fluorescence, suggesting oxidant conditions might impair heme biosynthesis by ferrochelatase. However, chronic hypoxia actually increased ferrochelatase activity in mouse pulmonary arteries. Thus, a reversal of factors increasing mitochondrial superoxide and oxidant effects that potentially influence remodeling signaling related to miR204 expression and perhaps iron availability needed for the biosynthesis of heme by the ferrochelatase reaction could be factors in the beneficial actions of ALA in pulmonary hypertension. PMID:25659899

  12. Inhibition of NF-κB activity in the hypothalamic paraventricular nucleus attenuates hypertension and cardiac hypertrophy by modulating cytokines and attenuating oxidative stress

    SciTech Connect

    Yu, Xiao-Jing; Zhang, Dong-Mei; Jia, Lin-Lin; Qi, Jie; Song, Xin-Ai; Tan, Hong; Cui, Wei; Chen, Wensheng; Zhu, Guo-Qing; Qin, Da-Nian; Kang, Yu-Ming

    2015-05-01

    We hypothesized that chronic inhibition of NF-κB activity 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), attenuating nuclear factor-κB (NF-κB) p65 and NAD(P)H oxidase in the PVN of young spontaneously hypertensive rats (SHR). Young normotensive Wistar–Kyoto (WKY) and SHR rats received bilateral PVN infusions with NF–κB inhibitor pyrrolidine dithiocarbamate (PDTC) or vehicle for 4 weeks. SHR rats had higher mean arterial pressure and cardiac hypertrophy as indicated by increased whole heart weight/body weight ratio, whole heart weight/tibia length ratio, left ventricular weight/tibia length ratio, cardiomyocyte diameters of the left cardiac ventricle, and mRNA expressions of cardiac atrial natriuretic peptide (ANP) and beta-myosin heavy chain (β-MHC). These SHR rats had higher PVN levels of proinflammatory cytokines (PICs), reactive oxygen species (ROS), the chemokine monocyte chemoattractant protein-1 (MCP-1), NAD(P)H oxidase activity, mRNA expression of NOX-2 and NOX-4, and lower PVN IL-10, and higher plasma levels of PICs and NE, and lower plasma IL-10. PVN infusion of NF-κB inhibitor PDTC attenuated all these changes. These findings suggest that NF-κB activation in the PVN increases sympathoexcitation and hypertensive response, which are associated with the increases of PICs and oxidative stress in the PVN; PVN inhibition of NF-κB activity attenuates PICs and oxidative stress in the PVN, thereby attenuates hypertension and cardiac hypertrophy. - Highlights: • Spontaneously hypertensive rats exhibit neurohormonal excitation in the PVN. • PVN inhibition of NF-κB attenuates hypertension-induced cardiac hypertrophy. • PVN inhibition of NF-κB attenuates hypertension-induced neurohormonal excitation. • PVN inhibition of NF-κB attenuates hypertension-induced imbalance of cytokines

  13. 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

  14. Brazilian Red Propolis Attenuates Hypertension and Renal Damage in 5/6 Renal Ablation Model

    PubMed Central

    Teles, Flávio; da Silva, Tarcilo Machado; da Cruz Júnior, Francisco Pessoa; Honorato, Vitor Hugo; de Oliveira Costa, Henrique; Barbosa, Ana Paula Fernandes; de Oliveira, Sabrina Gomes; Porfírio, Zenaldo; Libório, Alexandre Braga; Borges, Raquel Lerner; Fanelli, Camilla

    2015-01-01

    The pathogenic role of inflammation and oxidative stress in chronic kidney disease (CKD) is well known. Anti-inflammatories and antioxidant drugs has demonstrated significant renoprotection in experimental nephropathies. Moreover, the inclusion of natural antioxidants derived from food and herbal extracts (such as polyphenols, curcumin and lycopene) as an adjuvant therapy for slowing CKD progression has been largely tested. Brazilian propolis is a honeybee product, whose anti-inflammatory, antimicrobial and antioxidant effects have been widely shown in models of sepsis, cancer, skin irritation and liver fibrosis. Furthermore, previous studies demonstrated that this compound promotes vasodilation and reduces hypertension. However, potential renoprotective effects of propolis in CKD have never been investigated. The aim of this study was to evaluate the effects of a subtype of Brazilian propolis, the Red Propolis (RP), in the 5/6 renal ablation model (Nx). Adult male Wistar rats underwent Nx and were divided into untreated (Nx) and RP-treated (Nx+RP) groups, after 30 days of surgery; when rats already exhibited marked hypertension and proteinuria. Animals were observed for 90 days from the surgery day, when Nx+RP group showed significant reduction of hypertension, proteinuria, serum creatinine retention, glomerulosclerosis, renal macrophage infiltration and oxidative stress, compared to age-matched untreated Nx rats, which worsened progressively over time. In conclusion, RP treatment attenuated hypertension and structural renal damage in Nx model. Reduction of renal inflammation and oxidative stress could be a plausible mechanism to explain this renoprotection. PMID:25607548

  15. Calorie Restriction Attenuates Monocrotaline-induced Pulmonary Arterial Hypertension in Rats

    PubMed Central

    Ding, Mingge; Lei, Jingyi; Qu, Yinxian; Zhang, Huan; Xin, Weichuan; Ma, Feng; Liu, Shuwen; Li, Zhichao; Jin, Faguang

    2015-01-01

    Abstract: Calorie restriction (CR) is one of the most effective nonpharmacological interventions protecting against cardiovascular disease, such as hypertension in the systemic circulation. However, whether CR could attenuate pulmonary arterial hypertension (PAH) is largely unknown. The PAH model was developed by subjecting the rats to a single subcutaneous injection of monocrotaline. CR lowered mean pulmonary arterial pressure (mPAP) and reduced vascular remodeling and right ventricular hypertrophy in PAH rats. Meanwhile, CR attenuated endothelial dysfunction as evidenced by increased relaxation in response to acetylcholine. The beneficial effects of CR were associated with restored sirtuin-1 (SIRT1) expression and endothelial nitric oxide synthase (eNOS) phosphorylation and reduced eNOS acetylation in pulmonary arteries of PAH rats. To further clarify the role of SIRT1 in the protective effects of CR, adenoviral vectors for overexpression of SIRT1 were administered intratracheally at 1 day before monocrotaline injection. Overexpression of SIRT1 exhibited similar beneficial effects on mPAP and endothelial function, and increased eNOS phosphorylation and reduced eNOS acetylation in the absence of CR. Moreover, SIRT1 overexpression attenuated the increase in mPAP in hypoxia-induced PAH animals. Overall, the present data demonstrate that CR may serve as an effective treatment of PAH, and targeting the SIRT1/eNOS pathway may improve treatment of PAH. PMID:25636073

  16. Neutrophil Depletion Attenuates Placental Ischemia-Induced Hypertension in the Rat.

    PubMed

    Regal, Jean F; Lillegard, Kathryn E; Bauer, Ashley J; Elmquist, Barbara J; Loeks-Johnson, Alex C; Gilbert, Jeffrey S

    2015-01-01

    Preeclampsia is characterized by reduced placental perfusion with placental ischemia and hypertension during pregnancy. Preeclamptic women also exhibit a heightened inflammatory state and greater number of neutrophils in the vasculature compared to normal pregnancy. Since neutrophils are associated with tissue injury and inflammation, we hypothesized that neutrophils are critical to placental ischemia-induced hypertension and fetal demise. Using the reduced uteroplacental perfusion pressure (RUPP) model of placental ischemia-induced hypertension in the rat, we determined the effect of neutrophil depletion on blood pressure and fetal resorptions. Neutrophils were depleted with repeated injections of polyclonal rabbit anti-rat polymorphonuclear leukocyte (PMN) antibody (antiPMN). Rats received either antiPMN or normal rabbit serum (Control) on 13.5, 15.5, 17.5, and 18.5 days post conception (dpc). On 14.5 dpc, rats underwent either Sham surgery or clip placement on ovarian arteries and abdominal aorta to reduce uterine perfusion pressure (RUPP). On 18.5 dpc, carotid arterial catheters were placed and mean arterial pressure (MAP) was measured on 19.5 dpc. Neutrophil-depleted rats had reduced circulating neutrophils from 14.5 to 19.5 dpc compared to Control, as well as decreased neutrophils in lung and placenta on 19.5 dpc. MAP increased in RUPP Control vs Sham Control rats, and neutrophil depletion attenuated this increase in MAP in RUPP rats without any effect on Sham rats. The RUPP-induced increase in fetal resorptions and complement activation product C3a were not affected by neutrophil depletion. Thus, these data are the first to indicate that neutrophils play an important role in RUPP hypertension and that cells of the innate immune system may significantly contribute to pregnancy-induced hypertension. PMID:26135305

  17. Dahl salt-sensitive rats develop hypovitaminosis D and hyperparathyroidism when fed a standard diet

    NASA Technical Reports Server (NTRS)

    Thierry-Palmer, Myrtle; Cephas, Stacy; Sayavongsa, Phouyong; Doherty, Akins; Arnaud, Sara B.

    2005-01-01

    The Dahl salt-sensitive rat (S), a model for salt-sensitive hypertension, excretes protein-bound 25-hydroxyvitamin D (25-OHD) into urine when fed a low salt diet. Urinary 25-OHD increases during high salt intake. We tested the hypothesis that continuous loss of 25-OHD into urine would result in low plasma 25-OHD concentration in mature S rats raised on a standard diet. Dahl S and salt-resistant (R) male rats were raised to maturity (12-month-old) on a commercial rat diet (1% salt) and switched to 0.3% (low) or 2% (high) salt diets 3 weeks before euthanasia. Urine (24 h) was collected at the end of the dietary treatments. Urinary 25-OHD and urinary 25-OHD binding activity of S rats were three times that of R rats, resulting in lower plasma 25-OHD and 24,25-dihydroxyvitamin D concentrations in S rats than in R rats (P < 0.001). Plasma parathyroid hormone concentrations of S rats were twice that of R rats. S rats fed 2% salt had higher plasma 1,25-dihydroxyvitamin D concentrations than those fed 0.3% salt (P = 0.002). S rats excreted more calcium into urine than R rats (P < 0.001) and did not exhibit the expected calciuric response to salt. Proteinuria of the S rats was three times that of the R rats, suggesting kidney damage in the S rats. Low plasma 25-OHD and 24,25-dihydroxyvitamin D and high plasma 1,25-dihydroxyvitamin D and PTH concentrations seen in the mature S rats have also been reported for elderly patients with low-renin (salt-induced) hypertension. An implication of this study is that low vitamin D status may occur with age in salt-sensitive individuals, even when salt intake is normal.

  18. Melatonin attenuates hypertension-induced renal injury partially through inhibiting oxidative stress in rats

    PubMed Central

    QIAO, YU-FENG; GUO, WEN-JUAN; LI, LU; SHAO, SHAN; QIAO, XI; SHAO, JIN-JIN; ZHANG, QIONG; LI, RONG-SHAN; WANG, LI-HUA

    2016-01-01

    The aim of the present study was to investigate the protective effects of melatonin (MLT) on hypertension-induced renal injury and identify its mechanism of action. Twenty-four healthy male Wistar rats were divided into a sham control group (n=8), which was subjected to sham operation and received vehicle treatment (physiological saline intraperitoneally at 0.1 ml/100 g), a vehicle group (n=8), which was subjected to occlusion of the left renal artery and vehicle treatment, and the MLT group (n=8), which was subjected to occlusion of the left renal artery and treated with MLT (10 mg/kg/day). Pathological features of the renal tissues were determined using hematoxylin and eosin staining and Masson staining. Urine protein, serum creatinine (Scr), superoxide dismutase (SOD) and malondialdehyde (MDA) were determined. Immunohistochemical analysis was performed to determine the expression of heme oxygenase-1 (HO-1), intercellular adhesion molecule-1 (ICAM-1), inducible nitric oxide synthase (iNOS) and endothelial nitric oxide synthase (eNOS). Furthermore, reverse transcription polymerase chain reaction was conducted to determine the mRNA expression of HO-1, ICAM-1, eNOS and iNOS. A marked decrease in blood pressure was noticed in the MLT group at week 4 compared with that of the vehicle group (P<0.01). Furthermore, MLT treatment attenuated the infiltration of inflammatory cells and oedema/atrophy of renal tubules. MLT attenuated hypertension-induced increases in urine protein excretion, serum creatinine and MDA as well as decreases in SOD activity in renal tissues. Furthermore, MLT attenuated hypertension-induced increases in iNOS and ICAM-1 as well as decreases in eNOS and HO-1 expression at the mRNA and protein level. In conclusion, the results of the present study indicated that MLT had protective roles in hypertension-induced renal injury. Its mechanism of action is, at least in part, associated with the inhibition of oxidative stress. PMID:26531807

  19. Role of the Vascular Wall in Sodium Homeostasis and Salt Sensitivity

    PubMed Central

    Olde Engberink, Rik H.G.; Rorije, Nienke M.G.; Homan van der Heide, Jaap J.; van den Born, Bert-Jan H.

    2015-01-01

    Excessive sodium intake is associated with both hypertension and an increased risk of cardiovascular events, presumably because of an increase in extracellular volume. The extent to which sodium intake affects extracellular volume and BP varies considerably among individuals, discriminating subjects who are salt-sensitive from those who are salt-resistant. Recent experiments have shown that, other than regulation by the kidney, sodium homeostasis is also regulated by negatively charged glycosaminoglycans in the skin interstitium, where sodium is bound to glycosaminoglycans without commensurate effects on extracellular volume. The endothelial surface layer is a dynamic layer on the luminal side of the endothelium that is in continuous exchange with flowing blood. Because negatively charged glycosaminoglycans are abundantly present in this layer, it may act as an intravascular buffer compartment that allows sodium to be transiently stored. This review focuses on the putative role of the endothelial surface layer as a contributor to salt sensitivity, the consequences of a perturbed endothelial surface layer on sodium homeostasis, and the endothelial surface layer as a possible target for the treatment of hypertension and an expanded extracellular volume. PMID:25294232

  20. EP3 receptor deficiency attenuates pulmonary hypertension through suppression of Rho/TGF-β1 signaling.

    PubMed

    Lu, Ankang; Zuo, Caojian; He, Yuhu; Chen, Guilin; Piao, Lingjuan; Zhang, Jian; Xiao, Bing; Shen, Yujun; Tang, Juan; Kong, Deping; Alberti, Sara; Chen, Di; Zuo, Shenkai; Zhang, Qianqian; Yan, Shuai; Fei, Xiaochun; Yuan, Fei; Zhou, Bin; Duan, Shengzhong; Yu, Yu; Lazarus, Michael; Su, Yunchao; Breyer, Richard M; Funk, Colin D; Yu, Ying

    2015-03-01

    Pulmonary arterial hypertension (PAH) is commonly associated with chronic hypoxemia in disorders such as chronic obstructive pulmonary disease (COPD). Prostacyclin analogs are widely used in the management of PAH patients; however, clinical efficacy and long-term tolerability of some prostacyclin analogs may be compromised by concomitant activation of the E-prostanoid 3 (EP3) receptor. Here, we found that EP3 expression is upregulated in pulmonary arterial smooth muscle cells (PASMCs) and human distal pulmonary arteries (PAs) in response to hypoxia. Either pharmacological inhibition of EP3 or Ep3 deletion attenuated both hypoxia and monocrotaline-induced pulmonary hypertension and restrained extracellular matrix accumulation in PAs in rodent models. In a murine PAH model, Ep3 deletion in SMCs, but not endothelial cells, retarded PA medial thickness. Knockdown of EP3α and EP3β, but not EP3γ, isoforms diminished hypoxia-induced TGF-β1 activation. Expression of either EP3α or EP3β in EP3-deficient PASMCs restored TGF-β1 activation in response to hypoxia. EP3α/β activation in PASMCs increased RhoA-dependent membrane type 1 extracellular matrix metalloproteinase (MMP) translocation to the cell surface, subsequently activating pro-MMP-2 and promoting TGF-β1 signaling. Activation or disruption of EP3 did not influence PASMC proliferation. Together, our results indicate that EP3 activation facilitates hypoxia-induced vascular remodeling and pulmonary hypertension in mice and suggest EP3 inhibition as a potential therapeutic strategy for pulmonary hypertension. PMID:25664856

  1. EP3 receptor deficiency attenuates pulmonary hypertension through suppression of Rho/TGF-β1 signaling

    PubMed Central

    Lu, Ankang; Zuo, Caojian; He, Yuhu; Chen, Guilin; Piao, Lingjuan; Zhang, Jian; Xiao, Bing; Shen, Yujun; Tang, Juan; Kong, Deping; Alberti, Sara; Chen, Di; Zuo, Shenkai; Zhang, Qianqian; Yan, Shuai; Fei, Xiaochun; Yuan, Fei; Zhou, Bin; Duan, Shengzhong; Yu, Yu; Lazarus, Michael; Su, Yunchao; Breyer, Richard M.; Funk, Colin D.; Yu, Ying

    2015-01-01

    Pulmonary arterial hypertension (PAH) is commonly associated with chronic hypoxemia in disorders such as chronic obstructive pulmonary disease (COPD). Prostacyclin analogs are widely used in the management of PAH patients; however, clinical efficacy and long-term tolerability of some prostacyclin analogs may be compromised by concomitant activation of the E-prostanoid 3 (EP3) receptor. Here, we found that EP3 expression is upregulated in pulmonary arterial smooth muscle cells (PASMCs) and human distal pulmonary arteries (PAs) in response to hypoxia. Either pharmacological inhibition of EP3 or Ep3 deletion attenuated both hypoxia and monocrotaline-induced pulmonary hypertension and restrained extracellular matrix accumulation in PAs in rodent models. In a murine PAH model, Ep3 deletion in SMCs, but not endothelial cells, retarded PA medial thickness. Knockdown of EP3α and EP3β, but not EP3γ, isoforms diminished hypoxia-induced TGF-β1 activation. Expression of either EP3α or EP3β in EP3-deficient PASMCs restored TGF-β1 activation in response to hypoxia. EP3α/β activation in PASMCs increased RhoA-dependent membrane type 1 extracellular matrix metalloproteinase (MMP) translocation to the cell surface, subsequently activating pro–MMP-2 and promoting TGF-β1 signaling. Activation or disruption of EP3 did not influence PASMC proliferation. Together, our results indicate that EP3 activation facilitates hypoxia-induced vascular remodeling and pulmonary hypertension in mice and suggest EP3 inhibition as a potential therapeutic strategy for pulmonary hypertension. PMID:25664856

  2. Lysine deacetylase inhibition attenuates hypertension and is accompanied by acetylation of mineralocorticoid receptor instead of histone acetylation in spontaneously hypertensive rats.

    PubMed

    Seok, Young Mi; Lee, Hae Ahm; Park, Kwon Moo; Hwangbo, Mi-Hyang; Kim, In Kyeom

    2016-07-01

    Inhibition of lysine deacetylase (KDAC) attenuated development of hypertension in spontaneously hypertensive rats (SHRs). We hypothesized that KDAC inhibition attenuates hypertension and is accompanied by acetylation of mineralocorticoid receptors (MR) instead of histone acetylation in SHRs. Valproate (VPA, 0.71 % wt/vol), an inhibitor of class I KDACs, was administered in drinking water to 7-week-old SHRs and Wistar Kyoto rats for 11 weeks. MR acetylation was determined by immunoprecipitation with anti-MR antibody followed by western blot with anti-acetyl-lysine antibody. Expression levels of acetylated histone H3, KDACs, MR target genes, or MR corepressors in the kidney cortex were measured by using western blot analysis or real-time PCR. Recruitment of MR and RNA polymerase II (Pol II) and histone modifications on promoters of target genes were analyzed by performing a chromatin immunoprecipitation (ChIP) assay. Treatment of SHR with VPA increased MR acetylation without affecting MR expression, which attenuated development of hypertension in SHR VPA decreased expression of KDAC class I but globally increased acetylated histone H3. Although VPA treatment increased histone 3 acetylation (H3Ac) and trimethylation of the fourth lysine (H3K4me3) in the promoter regions of MR target genes, it decreased the expression of target genes as well as recruitment of MR and Pol II. These results suggest that KDAC inhibition attenuates the development of hypertension in SHRs and is accompanied by acetylation of MR that is independent of histone acetylation. PMID:27106211

  3. Responsiveness vs. basal activity of plasma ANG II as a determinant of arterial pressure salt sensitivity.

    PubMed

    Osborn, John W; Ariza-Nieto, Pilar; Collister, John P; Soucheray, Sandra; Zimmerman, Benjamin; Katz, Stephen

    2003-11-01

    Infusion of angiotensin II (ANG II) causes salt-sensitive hypertension. It is unclear whether this is due to the body's inability to suppress ANG II during increased salt intake or, rather, an elevated basal level of plasma ANG II itself. To distinguish between these mechanisms, Sprague-Dawley rats were instrumented with arterial and venous catheters for measurement of arterial pressure and infusion of drugs, respectively. The sensitivity of arterial pressure to salt was measured in four groups with the following treatments: 1) saline control (Con, n = 12); 2) administration of the angiotensin-converting enzyme inhibitor enalapril to block endogenous ANG II (ANG-Lo, n = 10); 3) administration of enalapril and 5 ng.kg(-1).min(-1) ANG II to clamp plasma ANG II at normal levels (ANG-Norm, n = 10); and 4) administration of enalapril and 20 ng.kg(-1).min(-1) ANG II to clamp ANG II at high levels (ANG-Hi, n = 10). Rats ingested a 0.4% NaCl diet for 3 days and then a 4.0% NaCl diet for 11 days. Arterial pressure of rats fed the 0.4% NaCl diet was lower in ANG-Lo (84 +/- 2 mmHg) compared with Con (101 +/- 3 mmHg) and ANG-Norm (98 +/- 4 mmHg) groups, whereas ANG-Hi rats were hypertensive (145 +/- 4 mmHg). Salt sensitivity was expressed as the change in arterial pressure divided by the change in sodium intake on the last day of the 4.0% NaCl diet. Salt sensitivity (in mmHg/meq Na) was lowest in Con rats (0.0 +/- 0.1) and progressed from ANG-Lo (0.8 +/- 0.2) to ANG-Norm (1.5 +/- 0.5) to ANG-Hi (3.5 +/- 0.5) rats. We conclude that the major determinant of salt sensitivity of arterial pressure is the basal level of plasma ANG II rather than the responsiveness of the renin-angiotensin system. PMID:12881218

  4. Melatonin attenuates hypertension-induced renal injury partially through inhibiting oxidative stress in rats.

    PubMed

    Qiao, Yu-Feng; Guo, Wen-Juan; Li, Lu; Shao, Shan; Qiao, Xi; Shao, Jin-Jin; Zhang, Qiong; Li, Rong-Shan; Wang, Li-Hua

    2016-01-01

    The aim of the present study was to investigate the protective effects of melatonin (MLT) on hypertension-induced renal injury and identify its mechanism of action. Twenty-four healthy male Wistar rats were divided into a sham control group (n=8), which was subjected to sham operation and received vehicle treatment (physiological saline intraperitoneally at 0.1 ml/100 g), a vehicle group (n=8), which was subjected to occlusion of the left renal artery and vehicle treatment, and the MLT group (n=8), which was subjected to occlusion of the left renal artery and treated with MLT (10 mg/kg/day). Pathological features of the renal tissues were determined using hematoxylin and eosin staining and Masson staining. Urine protein, serum creatinine (Scr), superoxide dismutase (SOD) and malondialdehyde (MDA) were determined. Immunohistochemical analysis was performed to determine the expression of heme oxygenase‑1 (HO‑1), intercellular adhesion molecule‑1 (ICAM‑1), inducible nitric oxide synthase (iNOS) and endothelial nitric oxide synthase (eNOS). Furthermore, reverse transcription polymerase chain reaction was conducted to determine the mRNA expression of HO‑1, ICAM‑1, eNOS and iNOS. A marked decrease in blood pressure was noticed in the MLT group at week 4 compared with that of the vehicle group (P<0.01). Furthermore, MLT treatment attenuated the infiltration of inflammatory cells and oedema/atrophy of renal tubules. MLT attenuated hypertension-induced increases in urine protein excretion, serum creatinine and MDA as well as decreases in SOD activity in renal tissues. Furthermore, MLT attenuated hypertension-induced increases in iNOS and ICAM‑1 as well as decreases in eNOS and HO‑1 expression at the mRNA and protein level. In conclusion, the results of the present study indicated that MLT had protective roles in hypertension‑induced renal injury. Its mechanism of action is, at least in part, associated with the inhibition of oxidative stress. PMID:26531807

  5. Salt sensitivity of children with low birth weight.

    PubMed

    Simonetti, Giacomo D; Raio, Luigi; Surbek, Daniel; Nelle, Mathias; Frey, Felix J; Mohaupt, Markus G

    2008-10-01

    Compromised intrauterine fetal growth leading to low birth weight (<2500 g) is associated with adulthood renal and cardiovascular disease. The aim of this study was to assess the effect of salt intake on blood pressure (salt sensitivity) in children with low birth weight. White children (n=50; mean age: 11.3+/-2.1 years) born with low (n=35) or normal (n=15) birth weight and being either small or appropriate for gestational age (n=25 in each group) were investigated. The glomerular filtration rate was calculated using the Schwartz formula, and renal size was measured by ultrasound. Salt sensitivity was assigned if mean 24-hour blood pressure increased by >or=3 mm Hg on a high-salt diet as compared with a controlled-salt diet. Baseline office blood pressure was higher and glomerular filtration rate lower in children born with low birth weight as compared with children born at term with appropriate weight (P<0.05). Salt sensitivity was present in 37% and 47% of all of the low birth weight and small for gestational age children, respectively, higher even than healthy young adults from the same region. Kidney length and volume (both P<0.0001) were reduced in low birth weight children. Salt sensitivity inversely correlated with kidney length (r(2)=0.31; P=0.005) but not with glomerular filtration rate. We conclude that a reduced renal mass in growth-restricted children poses a risk for a lower renal function and for increased salt sensitivity. Whether the changes in renal growth are causative or are the consequence of the same abnormal "fetal programming" awaits clarification. PMID:18695145

  6. Renal medullary microRNAs in Dahl salt-sensitive rats: miR-29b regulates several collagens and related genes.

    PubMed

    Liu, Yong; Taylor, Norman E; Lu, Limin; Usa, Kristie; Cowley, Allen W; Ferreri, Nicholas R; Yeo, Nan Cher; Liang, Mingyu

    2010-04-01

    MicroRNAs are endogenous repressors of gene expression. We examined microRNAs in the renal medulla of Dahl salt-sensitive rats and consomic SS-13(BN) rats. Salt-induced hypertension and renal injury in Dahl salt-sensitive rats, particularly medullary interstitial fibrosis, have been shown previously to be substantially attenuated in SS-13(BN) rats. Of 377 microRNAs examined, 5 were found to be differentially expressed between Dahl salt-sensitive rats and consomic SS-13(BN) rats receiving a high-salt diet. Real-time PCR analysis demonstrated that high-salt diets induced substantial upregulation of miR-29b in the renal medulla of SS-13(BN) rats but not in SS rats. miR-29b was predicted to regulate 20 collagen genes, matrix metalloproteinase 2 (Mmp2), integrin beta1 (Itgb1), and other genes related to the extracellular matrix. Expression of 9 collagen genes and Mmp2 was upregulated by a high-salt diet in the renal medulla of SS rats, but not in SS-13(BN) rats, an expression pattern opposite to miR-29b. Knockdown of miR-29b in the kidneys of SS-13(BN) rats resulted in upregulation of several collagen genes. miR-29b reduced expression levels of several collagen genes and Itgb1 in cultured rat renal medullary epithelial cells. Moreover, miR-29b suppressed the activity of luciferase when the reporter gene was linked to a 3'-untranslated segment of collagen genes Col1a1, Col3a1, Col4a1, Col5a1, Col5a2, Col5a3, Col7a1, Col8a1, Mmp2, or Itgb1 but not Col12a1. The result demonstrated broad effects of miR-29b on a large number of collagens and genes related to the extracellular matrix and suggested involvement of miR-29b in the protection from renal medullary injury in SS-13(BN) rats. PMID:20194304

  7. Variants in Striatin Gene are Associated with Salt Sensitive Blood Pressure in Mice and Humans

    PubMed Central

    Sun, Bei; Williams, Jonathan; Lasky-Su, Jessica; Baudrand, Rene; Yao, Tham; Moize, Burhanuddin; Hafiz, Wan M; Romero, Jose R.; Adler, Gail K.; Ferri, Claudio; Hopkins, Paul N.; Pojoga, Luminita H.; Williams, Gordon H.

    2015-01-01

    Striatin is a novel protein that interacts with steroid receptors and modifies rapid, non-genomic activity in vitro. We tested the hypothesis that striatin would in turn affect mineralocorticoid receptor function and consequently sodium, water, and blood pressure homeostasis in an animal model. We evaluated salt sensitivity of blood pressure in novel striatin heterozygote knockout mice. When compared with wild type, striatin heterozygote exhibited a significant increase in blood pressure when sodium intake was increased from restricted (0.03%) to liberal (1.6%) sodium). Further, renal expression of mineralocorticoid receptor and its genomic downstream targets serum/glucocoticoid-regulated kinase 1 and epithelial sodium channel were increased in striatin heterozygote versus wild type mice on liberal sodium intake while the pAkt/Akt ratio, readout of mineralocoriticoid receptor's rapid, non-genomic pathway, was reduced. To determine the potential clinical relevance of these findings, we tested the association between single nucleotide polymorphic variants of striatin gene and salt sensitivity of blood presure in 366 Caucasian hypertensive subjects. HapMap derived tagging single nucleotide polymorphisms identified an association between rs2540923 with salt sensitivity of blood pressure (OR, 6.25; 95% CI 1.7-20; P=0.01). These data provide the first in vivo evidence in humans and rodents that associates striatin with markers of mineralocoriticoid receptor activity. The data also support the hypothesis that the rapid, non-genomic mineralocoriticoid receptor pathway (mediated via striatin) has a role in modulating the interaction between salt intake and blood pressure. PMID:25368024

  8. Inhibition of reactive oxygen species in hypothalamic paraventricular nucleus attenuates the renin–angiotensin system and proinflammatory cytokines in hypertension

    SciTech Connect

    Su, Qing; Qin, Da-Nian; Wang, Fu-Xin; Ren, Jun; Li, Hong-Bao; Zhang, Meng; Yang, Qing; Miao, Yu-Wang; Yu, Xiao-Jing; Qi, Jie; Zhu, Zhiming; Zhu, Guo-Qing; Kang, Yu-Ming

    2014-04-15

    Aims: To explore whether reactive oxygen species (ROS) scavenger (tempol) in the hypothalamic paraventricular nucleus (PVN) attenuates renin–angiotensin system (RAS) and proinflammatory cytokines (PICs), and decreases the blood pressure and sympathetic activity in angiotensin II (ANG II)-induced hypertension. Methods and results: Male Sprague–Dawley rats were infused intravenously with ANG II (10 ng/kg per min) or normal saline (NS) for 4 weeks. These rats were treated with bilateral PVN infusion of oxygen free radical scavenger tempol (TEMP, 20 μg/h) or vehicle (artificial cerebrospinal fluid, aCSF) for 4 weeks. ANG II infusion resulted in increased mean arterial pressure (MAP) and renal sympathetic nerve activity (RSNA). These ANG II-infused rats also had higher levels of gp91{sup phox} (a subunit of NAD(P)H oxidase), angiotensin-converting enzyme (ACE), and interleukin-1beta (IL-1β) in the PVN than the control animals. Treatment with PVN infusion of TEMP attenuated the overexpression of gp91{sup phox}, ACE and IL-1β within the PVN, and decreased sympathetic activity and MAP in ANG II-infused rats. Conclusion: These findings suggest that ANG II infusion induces elevated PICs and oxidative stress in the PVN, which contribute to the sympathoexcitation in hypertension. Inhibition of reactive oxygen species in hypothalamic paraventricular nucleus attenuates the renin–angiotensin system, proinflammatory cytokines and oxidative stress in ANG II-induced hypertension. - Highlights: • The effect of chronic inhibiting PVN superoxide on hypertension was investigated. • ANG II infusion induced increased proinflammatory cytokines and superoxide in PVN. • ANG II infusion resulted in oxidative stress, sympathoexcitation and hypertension. • Chronic inhibiting PVN superoxide attenuates RAS and cytokines in hypertension.

  9. Attenuated muscle metaboreflex-induced pressor response during postexercise muscle ischemia in renovascular hypertension

    PubMed Central

    Spranger, Marty D.; Kaur, Jasdeep; Sala-Mercado, Javier A.; Machado, Tiago M.; Krishnan, Abhinav C.; Alvarez, Alberto

    2015-01-01

    During dynamic exercise, muscle metaboreflex activation (MMA; induced via partial hindlimb ischemia) markedly increases mean arterial pressure (MAP), and MAP is sustained when the ischemia is maintained following the cessation of exercise (postexercise muscle ischemia, PEMI). We previously reported that the sustained pressor response during PEMI in normal individuals is driven by a sustained increase in cardiac output (CO) with no peripheral vasoconstriction. However, we have recently shown that the rise in CO with MMA is significantly blunted in hypertension (HTN). The mechanisms sustaining the pressor response during PEMI in HTN are unknown. In six chronically instrumented canines, hemodynamic responses were observed during rest, mild exercise (3.2 km/h), MMA, and PEMI in the same animals before and after the induction of HTN [Goldblatt two kidney, one clip (2K1C)]. In controls, MAP, CO and HR increased with MMA (+52 ± 6 mmHg, +2.1 ± 0.3 l/min, and +37 ± 7 beats per minute). After induction of HTN, MAP at rest increased from 97 ± 3 to 130 ± 4 mmHg, and the metaboreflex responses were markedly attenuated (+32 ± 5 mmHg, +0.6 ± 0.2 l/min, and +11 ± 3 bpm). During PEMI in HTN, HR and CO were not sustained, and MAP fell to normal recovery levels. We conclude that the attenuated metaboreflex-induced HR, CO, and MAP responses are not sustained during PEMI in HTN. PMID:25632024

  10. Dietary calcium attenuates platelet aggregation and intracellular Ca2+ mobilization in spontaneously hypertensive rats

    NASA Technical Reports Server (NTRS)

    Otsuka, K.; Watanabe, M.; Yue, Q.; McCarron, D. A.; Hatton, D.

    1997-01-01

    Spontaneously hypertensive rats (SHR) are known to be blood pressure sensitive to dietary calcium. The effects of dietary calcium on platelet aggregation and intracellular Ca2+ mobilization were assessed by turbidimetric methods and fura-2 methods, respectively, in washed platelets of SHR. Ca2+ ATPase activity was examined in aortic membrane fractions. Six weeks of dietary calcium supplementation attenuated the increase of systolic blood pressure (SBP 199 +/- 16 v 170 +/- 9 mm Hg, P < .001) and thrombin-induced platelet aggregation (84.5 +/- 3.7 v 73.7 +/- 7.4%, P < .004) at 9 weeks of age. The ionomycin-induced intracellular calcium ([Ca2+]i) peak in the absence of external Ca2+, which reflects [Ca2+]i storage size, and thrombin-evoked [Ca2+]i release from [Ca2+]i storage were decreased by 2.0% Ca diet (472 +/- 55 v 370 +/- 23 nmol/L, P < .001, 339 +/- 29 v 278 +/- 33 nmol/L, P < .002). In addition, SBP was positively correlated with platelet aggregation (r = 0.703, P = .0088), thrombin-evoked [Ca2+]i (r = 0.739, P = .0044), and ionomycin-induced [Ca2+]i (r = 0.591, P = .0415), respectively. However, there was no significant effect of dietary calcium on Ca2+-ATPase activity in aortic membranes. These results suggest that dietary calcium supplementation had a beneficial effect on platelets of SHR by attenuating [Ca2+]i mobilization from [Ca2+]i storage. The hypotensive effect of dietary calcium might be associated with attenuated [Ca2+]i mobilization in SHR.

  11. Salvianolic acid A attenuates vascular remodeling in a pulmonary arterial hypertension rat model

    PubMed Central

    Chen, Yu-cai; Yuan, Tian-yi; Zhang, Hui-fang; Wang, Dan-shu; Yan, Yu; Niu, Zi-ran; Lin, Yi-huang; Fang, Lian-hua; Du, Guan-hua

    2016-01-01

    Aim: The current therapeutic approaches have a limited effect on the dysregulated pulmonary vascular remodeling, which is characteristic of pulmonary arterial hypertension (PAH). In this study we examined whether salvianolic acid A (SAA) extracted from the traditional Chinese medicine 'Dan Shen' attenuated vascular remodeling in a PAH rat model, and elucidated the underlying mechanisms. Methods: PAH was induced in rats by injecting a single dose of monocrotaline (MCT 60 mg/kg, sc). The rats were orally treated with either SAA (0.3, 1, 3 mg·kg−1·d−1) or a positive control bosentan (30 mg·kg−1·d−1) for 4 weeks. Echocardiography and hemodynamic measurements were performed on d 28. Then the hearts and lungs were harvested, the organ indices and pulmonary artery wall thickness were calculated, and biochemical and histochemical analysis were conducted. The levels of apoptotic and signaling proteins in the lungs were measured using immunoblotting. Results: Treatment with SAA or bosentan effectively ameliorated MCT-induced pulmonary artery remodeling, pulmonary hemodynamic abnormalities and the subsequent increases of right ventricular systolic pressure (RVSP). Furthermore, the treatments significantly attenuated MCT-induced hypertrophic damage of myocardium, parenchymal injury and collagen deposition in the lungs. Moreover, the treatments attenuated MCT-induced apoptosis and fibrosis in the lungs. The treatments partially restored MCT-induced reductions of bone morphogenetic protein type II receptor (BMPRII) and phosphorylated Smad1/5 in the lungs. Conclusion: SAA ameliorates the pulmonary arterial remodeling in MCT-induced PAH rats most likely via activating the BMPRII-Smad pathway and inhibiting apoptosis. Thus, SAA may have therapeutic potential for the patients at high risk of PAH. PMID:27180980

  12. A Blueberry-Enriched Diet Attenuates Nephropathy in a Rat Model of Hypertension via Reduction in Oxidative Stress

    PubMed Central

    Elks, Carrie M.; Reed, Scott D.; Mariappan, Nithya; Shukitt-Hale, Barbara; Joseph, James A.; Ingram, Donald K.; Francis, Joseph

    2011-01-01

    Objective and Background To assess renoprotective effects of a blueberry-enriched diet in a rat model of hypertension. Oxidative stress (OS) appears to be involved in the development of hypertension and related renal injury. Pharmacological antioxidants can attenuate hypertension and hypertension-induced renal injury; however, attention has shifted recently to the therapeutic potential of natural products as antioxidants. Blueberries (BB) have among the highest antioxidant capacities of fruits and vegetables. Methods and Results Male spontaneously hypertensive rats received a BB-enriched diet (2% w/w) or an isocaloric control diet for 6 or 12 weeks or 2 days. Compared to controls, rats fed BB-enriched diet for 6 or 12 weeks exhibited lower blood pressure, improved glomerular filtration rate, and decreased renovascular resistance. As measured by electron paramagnetic resonance spectroscopy, significant decreases in total reactive oxygen species (ROS), peroxynitrite, and superoxide production rates were observed in kidney tissues in rats on long-term dietary treatment, consistent with reduced pathology and improved function. Additionally, measures of antioxidant status improved; specifically, renal glutathione and catalase activities increased markedly. Contrasted to these observations indicating reduced OS in the BB group after long-term feeding, similar measurements made in rats fed the same diet for only 2 days yielded evidence of increased OS; specifically, significant increases in total ROS, peroxynitrite, and superoxide production rates in all tissues (kidney, brain, and liver) assayed in BB-fed rats. These results were evidence of “hormesis” during brief exposure, which dissipated with time as indicated by enhanced levels of catalase in heart and liver of BB group. Conclusion Long-term feeding of BB-enriched diet lowered blood pressure, preserved renal hemodynamics, and improved redox status in kidneys of hypertensive rats and concomitantly demonstrated

  13. Waon therapy attenuates cardiac hypertrophy and promotes myocardial capillary growth in hypertensive rats: a comparative study with fluvastatin.

    PubMed

    Ihori, Hiroyuki; Nozawa, Takashi; Sobajima, Mitsuo; Shida, Takuya; Fukui, Yasutaka; Fujii, Nozomu; Inoue, Hiroshi

    2016-08-01

    Cardiac hypertrophy and fibrosis in heart failure with preserved ejection fraction are associated with a pro-inflammatory state and reduced NO bioavailability. Effects on myocardial structural and molecular alterations were compared between Waon therapy (WT; repeated dry sauna therapy) and statin in hypertensive rats. Seven-week-old Dahl salt-sensitive rats were assigned to 4 groups: low-salt (LS) diet, high-salt (HS) diet, HS diet with oral fluvastatin (FL; 10 mg/kg/day for 4 weeks) starting from the age of 9 weeks, and HS diet with WT treatment in a far-infrared dry sauna (39 °C for 15 min followed by 34 °C for 20 min once daily for 4 weeks). HS rats developed left ventricular (LV) hypertrophy with preserved LV systolic function. WT reduced LV wall thickness and myocyte cross-sectional area along with decreased levels of myocardial ANP and BNP mRNA expression compared with HS rats. Reduction in LV fibrosis and increase in capillary density in WT animals were accompanied by reductions in myocardial levels of TGF-β1, MMP2, p22(phox) and gp91(phox) mRNA expression, and increases in myocardial levels of VEGF and HSP90 mRNA and phosphorylated eNOS protein. These effects were comparable between WT and FL animals. WT improves structural and molecular alterations in salt-induced hypertensive rats similarly to fluvastatin. PMID:26686369

  14. Ultrafine carbon black attenuates the antihypertensive effect of captopril in spontaneously hypertensive rats.

    PubMed

    Zhang, Xinru; Chen, Yiyong; Wei, Hongying; Qin, Yu; Hao, Yu; Zhu, Yidan; Deng, Furong; Guo, Xinbiao

    2014-12-01

    Particulate matter (PM) has been associated with increased blood pressure (BP) by affecting renin-angiotensin system (RAS) on a systemic level in spontaneously hypertensive rats (SHR). RAS in SHR is also an important target for the angiotensin converting enzyme (ACE) inhibitors such as captopril. We aimed to determine if ultrafine carbon black (UCB) could affect antihypertensive effect of captopril in SHR. The rats were randomly divided into six groups. Group 1 did not receive intratracheal instillation; group 2 received saline instillation plus captopril administration; groups 3, 4 and 5 received 0.15 mg/kg, 0.45 mg/kg and 1.35 mg/kg UCB per instillation plus captopril administration, respectively; group 6 received 1.35 mg/kg UCB instillation only. Rats in the above groups were intratracheally instilled with saline or UCB once every two days for three times and captopril was administered to group 2-5 after the final UCB treatment, once a day for one week. The BP was measured 24 h after each intratracheal instillation. During captopril administration and 24 h after last captopril administration, we measured BP every two days for four times. Our results showed that UCB at the dose of 1.35 mg/kg induced pulmonary and systemic inflammation in SHR. Captopril reduced BP in rats exposed to 0, 0.15 and 0.45 mg/kg UCB seven and eleven days after the first UCB instillation, and had no effect on BP in rats exposed to 1.35 mg/kg UCB. Captopril also reduced angiotensin II (AngII) in rats exposed to saline. The reduction, however, was attenuated with increasing doses of UCB. We conclude that UCB attenuated the antihypertensive effect of captopril in SHR, and the effect was accompanied by a systemic increase in the concentration of AngII. PMID:25472475

  15. Overexpression of angiotensin-converting enzyme 2 attenuates tonically active glutamatergic input to the rostral ventrolateral medulla in hypertensive rats

    PubMed Central

    Wang, Yang-Kai; Shen, Du; Hao, Qiang; Yu, Qiang; Wu, Zhao-Tang; Deng, Yu; Chen, Yan-Fang; Yuan, Wen-Jun; Hu, Qi-Kuan; Su, Ding-Feng

    2014-01-01

    The rostral ventrolateral medulla (RVLM) plays a key role in cardiovascular regulation. It has been reported that tonically active glutamatergic input to the RVLM is increased in hypertensive rats, whereas angiotensin-converting enzyme 2 (ACE2) in the brain has been suggested to be beneficial to hypertension. This study was designed to determine the effect of ACE2 gene transfer into the RVLM on tonically active glutamatergic input in spontaneously hypertensive rats (SHRs). Lentiviral particles containing enhanced green fluorescent protein (lenti-GFP) or ACE2 (lenti-ACE2) were injected bilaterally into the RVLM. Both protein expression and activity of ACE2 in the RVLM were increased in SHRs after overexpression of ACE2. A significant reduction in blood pressure and heart rate in SHRs was observed 6 wk after lenti-ACE2 injected into the RVLM. The concentration of glutamate in microdialysis fluid from the RVLM was significantly reduced by an average of 61% in SHRs with lenti-ACE2 compared with lenti-GFP. ACE2 overexpression significantly attenuated the decrease in blood pressure and renal sympathetic nerve activity evoked by bilateral injection of the glutamate receptor antagonist kynurenic acid (2.7 nmol in 100 nl) into the RVLM in SHRs. Therefore, we suggest that ACE2 overexpression in the RVLM attenuates the enhanced tonically active glutamatergic input in SHRs, which may be an important mechanism underlying the beneficial effect of central ACE2 to hypertension. PMID:24838502

  16. Tumor necrosis factor-α inhibition attenuates middle cerebral artery remodeling but increases cerebral ischemic damage in hypertensive rats

    PubMed Central

    Girgla, Saavia S.; Moreno, Guillermo; McClain, Jonathon L.; Dorrance, Anne M.

    2014-01-01

    Hypertension causes vascular inflammation evidenced by an increase in perivascular macrophages and proinflammatory cytokines in the arterial wall. Perivascular macrophage depletion reduced tumor necrosis factor (TNF)-α expression in cerebral arteries of hypertensive rats and attenuated inward remodeling, suggesting that TNF-α might play a role in the remodeling process. We hypothesized that TNF-α inhibition would improve middle cerebral artery (MCA) structure and reduce damage after cerebral ischemia in hypertensive rats. Six-week-old male stroke-prone spontaneously hypertensive rats (SHRSP) were treated with the TNF-α inhibitor etanercept (ETN; 1.25 mg·kg−1·day−1 ip daily) or PBS (equivolume) for 6 wk. The myogenic tone generation, postischemic dilation, and passive structure of MCAs were assessed by pressure myography. Cerebral ischemia was induced by MCA occlusion (MCAO). Myogenic tone was unchanged, but MCAs from SHRSP + ETN had larger passive lumen diameter and reduced wall thickness and wall-to-lumen ratio. Cerebral infarct size was increased in SHRSP + ETN after transient MCAO, despite an improvement in dilation of nonischemic MCA. The increase in infarct size was linked to a reduction in the number of microglia in the infarct core and upregulation of markers of classical macrophage/microglia polarization. There was no difference in infarct size after permanent MCAO or when untreated SHRSP subjected to transient MCAO were given ETN at reperfusion. Our data suggests that TNF-α inhibition attenuates hypertensive MCA remodeling but exacerbates cerebral damage following ischemia/reperfusion injury likely due to inhibition of the innate immune response of the brain. PMID:25015967

  17. 17β-Estradiol Attenuates Conduit Pulmonary Artery Mechanical Property Changes With Pulmonary Arterial Hypertension.

    PubMed

    Liu, Aiping; Tian, Lian; Golob, Mark; Eickhoff, Jens C; Boston, Madison; Chesler, Naomi C

    2015-11-01

    Pulmonary arterial hypertension (PAH), a rapidly fatal vascular disease, strikes women more often than men. Paradoxically, female PAH patients have better prognosis and survival rates than males. The female sex hormone 17β-estradiol has been linked to the better outcome of PAH in females; however, the mechanisms by which 17β-estradiol alters PAH progression and outcomes remain unclear. Because proximal pulmonary arterial (PA) stiffness, one hallmark of PAH, is a powerful predictor of mortality and morbidity, we hypothesized that 17β-estradiol attenuates PAH-induced changes in mechanical properties in conduit proximal PAs, which imparts hemodynamic and energetic benefits to right ventricular function. To test this hypothesis, female mice were ovariectomized and treated with 17β-estradiol or placebo. PAH was induced in mice using SU5416 and chronic hypoxia. Extra-lobar left PAs were isolated and mechanically tested ex vivo to study both static and frequency-dependent mechanical behaviors in the presence or absence of smooth muscle cell activation. Our static mechanical test showed significant stiffening of large PAs with PAH (P<0.05). 17β-Estradiol restored PA compliance to control levels. The dynamic mechanical test demonstrated that 17β-estradiol protected the arterial wall from the PAH-induced frequency-dependent decline in dynamic stiffness and loss of viscosity with PAH (P<0.05). As demonstrated by the in vivo measurement of PA hemodynamics via right ventricular catheterization, modulation by 17β-estradiol of mechanical proximal PAs reduced pulsatile loading, which contributed to improved ventricular-vascular coupling. This study provides a mechanical mechanism for delayed disease progression and better outcome in female PAH patients and underscores the therapeutic potential of 17β-estradiol in PAH. PMID:26418020

  18. Renalase attenuates hypertension, renal injury and cardiac remodelling in rats with subtotal nephrectomy.

    PubMed

    Yin, Jianyong; Lu, Zeyuan; Wang, Feng; Jiang, Zhenzhen; Lu, Limin; Miao, Naijun; Wang, Niansong

    2016-06-01

    Chronic kidney disease is associated with higher risk of cardiovascular complication and this interaction can lead to accelerated dysfunction in both organs. Renalase, a kidney-derived cytokine, not only protects against various renal diseases but also exerts cardio-protective effects. Here, we investigated the role of renalase in the progression of cardiorenal syndrome (CRS) after subtotal nephrectomy. Sprague-Dawley rats were randomly subjected to sham operation or subtotal (5/6) nephrectomy (STNx). Two weeks after surgery, sham rats were intravenously injected with Hanks' balanced salt solution (sham), and STNx rats were randomly intravenously injected with adenovirus-β-gal (STNx+Ad-β-gal) or adenovirus-renalase (STNx+Ad-renalase) respectively. After 4 weeks of therapy, Ad-renalase administration significantly restored plasma, kidney and heart renalase expression levels in STNx rats. We noticed that STNx rats receiving Ad-renalase exhibited reduced proteinuria, glomerular hypertrophy and interstitial fibrosis after renal ablation compared with STNx rats receiving Ad-β-gal; these changes were associated with significant decreased expression of genes for fibrosis markers, proinflammatory cytokines and nicotinamide adenine dinucleotide phosphate (NADPH) oxidase components. At the same time, systemic delivery of renalase attenuated hypertension, cardiomyocytes hypertrophy and cardiac interstitial fibrosis; prevented cardiac remodelling through inhibition of pro-fibrotic genes expression and phosphorylation of extracellular signal-regulated kinase (ERK)-1/2. In summary, these results indicate that renalase protects against renal injury and cardiac remodelling after subtotal nephrectomy via inhibiting inflammation, oxidative stress and phosphorylation of ERK-1/2. Renalase shows potential as a therapeutic target for the prevention and treatment of CRS in patients with chronic kidney disease. PMID:26923216

  19. Attenuation of the extract from Moringa oleifera on monocrotaline-induced pulmonary hypertension in rats.

    PubMed

    Chen, Kang-Hu; Chen, Yi-Jui; Yang, Chao-Hsun; Liu, Kuo-Wei; Chang, Junn-Liang; Pan, Shwu-Fen; Lin, Tzer-Bin; Chen, Mei-Jung

    2012-02-29

    The purpose of this study was to determine the effects of an extract from Moringa oleifera (MO) on the development of monocrotaline (MCT)-induced pulmonary hypertension (PH) in Wistar rats. An ethanol extraction was performed on dried MO leaves, and HPLC analysis identified niaziridin and niazirin in the extract. PH was induced with a single subcutaneous injection of MCT (60 mg/kg) which resulted in increases in pulmonary arterial blood pressure (Ppa) and in thickening of the pulmonary arterial medial layer in the rats. Three weeks after induction, acute administration of the MO extract to the rats decreased Ppa in a dose-dependent manner that reached statistical significance at a dose of 4.5 mg of freeze-dried extract per kg body weight. The reduction in Ppa suggested that the extract directly relaxed the pulmonary arteries. To assay the effects of chronic administration of the MO extract on PH, control, MCT and MCT+MO groups were designated. Rats in the control group received a saline injection; the MCT and MCT+MO groups received MCT to induce PH. During the third week after MCT treatment, the MCT+MO group received daily i.p. injections of the MO extract (4.5 mg of freeze-dried extract/kg of body weight). Compared to the control group, the MCT group had higher Ppa and thicker medial layers in the pulmonary arteries. Chronic treatments with the MO extract reversed the MCT-induced changes. Additionally, the MCT group had a significant elevation in superoxide dismutase activity when normalized by the MO extract treatments. In conclusion, the MO extract successfully attenuated the development of PH via direct vasodilatation and a potential increase in antioxidant activity. PMID:22242951

  20. Increasing or stabilizing renal epoxyeicosatrienoic acid production attenuates abnormal renal function and hypertension in obese rats.

    PubMed

    Huang, Hui; Morisseau, Christophe; Wang, JingFeng; Yang, Tianxin; Falck, John R; Hammock, Bruce D; Wang, Mong-Heng

    2007-07-01

    Since epoxyeicosatrienoic acids (EETs) affect sodium reabsorption in renal tubules and dilate the renal vasculature, we have examined their effects on renal hemodynamics and sodium balance in male rats fed a high-fat (HF) diet by fenofibrate, a peroxisome proliferator-activated receptor-alpha (PPAR-alpha) agonist and an inducer of cytochrome P-450 (CYP) epoxygenases; by N-methanesulfonyl-6-(2-proparyloxyphenyl)hexanamide (MSPPOH), a selective EET biosynthesis inhibitor; and by 12-(3-adamantane-1-yl-ureido)dodecanoic acid (AUDA), a selective inhibitor of soluble epoxide hydrolase. In rats treated with fenofibrate (30 mg.kg(-1).day(-1) ig) or AUDA (50 mg/l in drinking water) for 2 wk, mean arterial pressure, renal vascular resistance, and glomerular filtration rate were lower but renal blood flow was higher than in vehicle-treated control rats. In addition, fenofibrate and AUDA decreased cumulative sodium balance in the HF rats. Treatment with MSPPOH (20 mg.kg(-1).day(-1) iv) + fenofibrate for 2 wk reversed renal hemodynamics and sodium balance to the levels in control HF rats. Moreover, fenofibrate caused a threefold increase in renal cortical CYP epoxygenase activity, whereas the fenofibrate-induced elevation of this activity was attenuated by MSPPOH. Western blot analysis showed that fenofibrate induced the expression of CYP epoxygenases in renal cortex and microvessels and that the induction effect of fenofibrate was blocked by MSPPOH. These results demonstrate that the fenofibrate-induced increase of CYP epoxygenase expression and the AUDA-induced stabilization of EET production in the kidneys cause renal vascular dilation and reduce sodium retention, contributing to the improvement of abnormal renal hemodynamics and hypertension in HF rats. PMID:17442729

  1. Selective activation of angiotensin AT2 receptors attenuates progression of pulmonary hypertension and inhibits cardiopulmonary fibrosis

    PubMed Central

    Bruce, E; Shenoy, V; Rathinasabapathy, A; Espejo, A; Horowitz, A; Oswalt, A; Francis, J; Nair, A; Unger, T; Raizada, M K; Steckelings, U M; Sumners, C; Katovich, M J

    2015-01-01

    Background and Purpose Pulmonary hypertension (PH) is a devastating disease characterized by increased pulmonary arterial pressure, which progressively leads to right-heart failure and death. A dys-regulated renin angiotensin system (RAS) has been implicated in the development and progression of PH. However, the role of the angiotensin AT2 receptor in PH has not been fully elucidated. We have taken advantage of a recently identified non-peptide AT2 receptor agonist, Compound 21 (C21), to investigate its effects on the well-established monocrotaline (MCT) rat model of PH. Experimental Approach A single s.c. injection of MCT (50 mg·kg−1) was used to induce PH in 8-week-old male Sprague Dawley rats. After 2 weeks of MCT administration, a subset of animals began receiving either 0.03 mg·kg−1 C21, 3 mg·kg−1 PD-123319 or 0.5 mg·kg−1 A779 for an additional 2 weeks, after which right ventricular haemodynamic parameters were measured and tissues were collected for gene expression and histological analyses. Key Results Initiation of C21 treatment significantly attenuated much of the pathophysiology associated with MCT-induced PH. Most notably, C21 reversed pulmonary fibrosis and prevented right ventricular fibrosis. These beneficial effects were associated with improvement in right heart function, decreased pulmonary vessel wall thickness, reduced pro-inflammatory cytokines and favourable modulation of the lung RAS. Conversely, co-administration of the AT2 receptor antagonist, PD-123319, or the Mas antagonist, A779, abolished the protective actions of C21. Conclusions and Implications Taken together, our results suggest that the AT2 receptor agonist, C21, may hold promise for patients with PH. PMID:25522140

  2. Differences in genotype frequencies of salt-sensitive genes between fishing and nonfishing communities in Japan

    PubMed Central

    Harada, Masanori; Takeshima, Taro; Okayama, Masanobu; Kajii, Eiji

    2016-01-01

    Purpose To identify the differences in genotype frequencies of salt-sensitive genes between residents of fishing communities (FCs) and nonfishing communities (NFCs). Methods The subjects included 18,156 individuals (8,043 males [44%] and 10,113 females [56%]; average age: 57.2±16.1 years) from the general population who were registered with large-scale genome banks and resided in 30 prefectures and 78 different regions in Japan. The measurement items were age, sex, blood pressure, presence or absence of hypertension, body mass index, alcohol consumption, and smoking habit. Furthermore, to analyze the genotype frequencies of salt-sensitive genes, α-adducin 1 (ADD1), angiotensinogen (AGT), angiotensin II receptor type 1 (AT1), and guanine nucleotide-binding protein β peptide 3 (GNB3) were measured. According to the 2004 government classification of municipalities (cities, towns, and villages), communities existing in areas bordering an ocean and with an ocean port were defined as FCs (28 areas). The others were defined as NFCs (50 areas). A logistic regression model was used for comparison of genotype frequencies between subjects residing in FCs and NFCs. Results Of the included subjects, 4,916 (27.0%) and 13,240 (73.0%) resided in FCs and NFCs, respectively. In FCs, the mean age was 59.4±16.7 years and men accounted for 41.0% of the cohort (n=2,015). In NFCs, the mean age was 56.4±15.8 years and men accounted for 45.5% of the cohort (n=6,028). The adjusted odds ratios of the AA and AG genotypes compared with the GG genotype for AGT were 0.80 (95% confidence interval [CI]: 0.68–0.95) and 0.76 (95% CI: 0.64–0.91), respectively. The adjusted odds ratio of the CC genotype compared with AA for AT1 was 0.63 (95% CI: 0.40–0.93). Conclusion The incidence of the salt-sensitive genotypes AGT and AT1 in residents of FCs were significantly lower than in NFCs. PMID:27110136

  3. Intracerebroventricular infusion of the (Pro)renin receptor antagonist PRO20 attenuates deoxycorticosterone acetate-salt-induced hypertension.

    PubMed

    Li, Wencheng; Sullivan, Michelle N; Zhang, Sheng; Worker, Caleb J; Xiong, Zhenggang; Speth, Robert C; Feng, Yumei

    2015-02-01

    We previously reported that binding of prorenin to the (pro)renin receptor (PRR) plays a major role in brain angiotensin II formation and the development of deoxycorticosterone acetate (DOCA)-salt hypertension. Here, we designed and developed an antagonistic peptide, PRO20, to block prorenin binding to the PRR. Fluorescently labeled PRO20 bound to both mouse and human brain tissues with dissociation constants of 4.4 and 1.8 nmol/L, respectively. This binding was blocked by coincubation with prorenin and was diminished in brains of neuron-specific PRR-knockout mice, indicating specificity of PRO20 for PRR. In cultured human neuroblastoma cells, PRO20 blocked prorenin-induced calcium influx in a concentration- and AT(1) receptor-dependent manner. Intracerebroventricular infusion of PRO20 dose-dependently inhibited prorenin-induced hypertension in C57Bl6/J mice. Furthermore, acute intracerebroventricular infusion of PRO20 reduced blood pressure in both DOCA-salt and genetically hypertensive mice. Chronic intracerebroventricular infusion of PRO20 attenuated the development of hypertension and the increase in brain hypothalamic angiotensin II levels induced by DOCA-salt. In addition, chronic intracerebroventricular infusion of PRO20 improved autonomic function and spontaneous baroreflex sensitivity in mice treated with DOCA-salt. In summary, PRO20 binds to both mouse and human PRRs and decreases angiotensin II formation and hypertension induced by either prorenin or DOCA-salt. Our findings highlight the value of the novel PRR antagonist, PRO20, as a lead compound for a novel class of antihypertensive agents and as a research tool to establish the validity of brain PRR antagonism as a strategy for treating hypertension. PMID:25421983

  4. Expression of Heme Oxygenase-1 in Thick Ascending Loop of Henle Attenuates Angiotensin II-Dependent Hypertension

    PubMed Central

    Drummond, Heather A.; Gousette, Monette U.; Storm, Megan V.; Abraham, Nader G.; Csongradi, Eva

    2012-01-01

    Kidney-specific induction of heme oxygenase-1 (HO-1) attenuates the development of angiotensin II (Ang II) -dependent hypertension, but the relative contribution of vascular versus tubular induction of HO-1 is unknown. To determine the specific contribution of thick ascending loop of Henle (TALH) -derived HO-1, we generated a transgenic mouse in which the uromodulin promoter controlled expression of human HO-1. Quantitative RT-PCR and confocal microscopy confirmed successful localization of the HO-1 transgene to TALH tubule segments. Medullary HO activity, but not cortical HO activity, was significantly higher in transgenic mice than control mice. Enhanced TALH HO-1 attenuated the hypertension induced by Ang II delivered by an osmotic minipump for 10 days (139±3 versus 153±2 mmHg in the transgenic and control mice, respectively; P<0.05). The lower blood pressure in transgenic mice associated with a 60% decrease in medullary NKCC2 transporter expression determined by Western blot. Transgenic mice also exhibited a 36% decrease in ouabain-sensitive sodium reabsorption and a significantly attenuated response to furosemide in isolated TALH segments,. In summary, these results show that increased levels of HO-1 in the TALH can lower blood pressure by a mechanism that may include alterations in NKCC2-dependent sodium reabsorption. PMID:22323644

  5. Genistein attenuates low temperature induced pulmonary hypertension in broiler chicks by modulating endothelial function.

    PubMed

    Yang, Ying; Gao, Mingyu; Wu, Zhenlong; Guo, Yuming

    2010-12-15

    Pulmonary arterial hypertension is characterized by high pulmonary blood pressure, vascular remodeling and right ventricular hypertrophy. In the present study, we investigated whether genistein would prevent the development of low temperature-induced pulmonary hypertension in broilers. Hemodynamic parameters, vascular remodeling, the expression of endothelial nitric oxide and endothelin-1 content in lung tissue were evaluated. The results demonstrated that genistein significantly reduced pulmonary arterial hypertension and suppressed pulmonary arterial vascular remodeling without affecting broilers' performance. The beneficial effects appeared to be mediated by restoring endothelial function especially endothelial nitric oxide and endothelin-1, two critical vasoactive molecules that associated with the development of hypertension. Genistein supplementation might be a potential therapeutic strategy for the treatment of pulmonary hypertension. PMID:20854807

  6. Hypertension.

    PubMed

    Oparil, S; Calhoun, D A

    1989-03-01

    An estimated 58 million Americans are at increased risk of morbidity and premature death due to high blood pressure (BP) and require some type of therapy or systematic monitoring. This article focuses on recent advances in our understanding of the pathogenesis of hypertension, new approaches to the diagnosis and treatment of secondary hypertension, and current views of the most appropriate nonpharmacologic and pharmacologic therapy for essential hypertension. In view of the extremely high prevalence of the disorder, emphasis is placed on efficient and cost-effective strategies for diagnosing and managing the hypertensive patient. Recent evidence indicates that nonpharmacologic therapy, including dietary potassium and calcium supplements, reduction of salt intake, weight loss for the obese patient, regular exercise, a diet high in fiber and low in cholesterol and saturated fats, smoking cessation, and moderation of alcohol consumption produces significant sustained reductions in BP while reducing overall cardiovascular risk. Accordingly, nonpharmacologic antihypertensive therapy should be included in the treatment of all hypertensive patients. In persons with mild hypertension, nonpharmacologic approaches may adequately reduce BP, thereby avoiding the expense and potential side effects of drug therapy. In patients with more severe hypertension, nonpharmacologic therapy, used in conjunction with pharmacologic therapy, can reduce the dosage of antihypertensive medications necessary for BP control. Patients treated with nonpharmacologic therapy only should be followed closely, and if BP control is not satisfactory, drug therapy should be added. The large number of drugs available for use in hypertension treatment, coupled with our rapidly expanding knowledge of the pathophysiology of hypertension and of the adverse effects of these drugs in individual patient groups, make it possible to individualize antihypertensive treatment. When used as monotherapy, most agents

  7. Curcumin attenuates cardiac fibrosis in spontaneously hypertensive rats through PPAR-γ activation

    PubMed Central

    Meng, Zhe; Yu, Xin-hui; Chen, Jun; Li, Ling; Li, Sheng

    2014-01-01

    Aim: To investigate the effects of curcumin (Cur) on cardiac fibrosis in spontaneously hypertensive rats (SHRs) and the mechanisms underlying the anti-fibrotic effect of Cur in rat cardiac fibroblasts (CFs) in vitro. Methods: SHRs were orally treated with Cur (100 mg·kg−1·d−1) or Cur (100 mg·kg−1·d−1) plus the PPAR-γ antagonist GW9662 (1 mg·kg−1·d−1) for 12 weeks. Cultured CFs were treated with angiotensin II (Ang II, 0.1 μmol/L) in vitro. The expression of relevant proteins and mRNAs was analyzed using Western blotting and real-time PCR, respectively. The expression and activity of peroxisome proliferator-activated receptor-γ (PPAR-γ) were detected using Western blotting and a DNA-binding assay, respectively. Results: Treatment of SHRs with Cur significantly decreased systolic blood pressure, blood Ang II concentration, heart weight/body weight ratio and left ventricle weight/body weight ratio, with concurrently decreased expression of connective tissue growth factor (CTGF), plasminogen activator inhibitor (PAI)-1, collagen III (Col III) and fibronectin (FN), and increased expression and activity of PPAR-γ in the left ventricle. Co-treatment with GW9662 partially abrogated the anti-fibrotic effects of Cur in SHRs. Pretreatment of CFs with Cur (5, 10, 20 μmol/L) dose-dependently inhibited Ang II-induced expression of CTGF, PAI-1, Col III and FN, and increased the expression and binding activity of PPAR-γ. Pretreatment with GW9662 partially reversed anti-fibrotic effects of Cur in vitro. Furthermore, pretreatment of CFs with Cur inhibited Ang II-induced expression of transforming growth factor-β1 (TGF-β1) and phosphorylation of Smad2/3, which were reversed by GW9662. Conclusion: Cur attenuates cardiac fibrosis in SHRs and inhibits Ang II-induced production of CTGF, PAI-1 and ECM in CFs in vitro. The crosstalk between PPAR-γ and TGF-β1/Smad2/3 signaling is involved in the anti-fibrotic and anti-proliferative effects of Cur. PMID:25132338

  8. Neuronal Uptake of Nanoformulated Superoxide Dismutase and Attenuation of Angiotensin II-Dependent Hypertension Following Central Administration

    PubMed Central

    Savalia, Krupa; Manickam, Devika S.; Rosenbaugh, Erin G.; Tian, Jun; Ahmad, Iman M.; Kabanov, Alexander V.; Zimmerman, Matthew C.

    2014-01-01

    Excessive production of superoxide (O2•−) in the central nervous system has been widely implicated in the pathogenesis of cardiovascular diseases, including chronic heart failure and hypertension. In an attempt to overcome the failed therapeutic impact of currently available antioxidants in cardiovascular disease, we developed a nanomedicine-based delivery system for the O2•− scavenging enzyme, copper/zinc superoxide dismutase (CuZnSOD), in which CuZnSOD protein is electrostatically bound to poly-L-lysine (PLL50)-polyethylene glycol (PEG) block co-polymer to form CuZnSOD nanozyme. Different formulations of CuZnSOD nanozyme are covalently stabilized by either reducible or non-reducible crosslinked bonds between the PLL50-PEG polymers. Herein, we tested the hypothesis that PLL50-PEG CuZnSOD nanozyme delivers active CuZnSOD protein to neurons and decreases blood pressure in a mouse model of AngII-dependent hypertension. As determined by electron paramagnetic resonance (EPR) spectroscopy, nanozymes retain full SOD enzymatic activity as compared to native CuZnSOD protein. Non-reducible CuZnSOD nanozyme delivers active CuZnSOD protein to central neurons in culture (CATH.a neurons) without inducing significant neuronal toxicity. In vivo studies conducted in adult male C57BL/6 mice demonstrate that hypertension established by chronic subcutaneous infusion of AngII is significantly attenuated for up to 7 days following a single intracerebroventricular (ICV) injection of non-reducible nanozyme. These data indicate the efficacy of non-reducible PLL50-PEG CuZnSOD nanozyme in counteracting excessive O2•− and decreasing blood pressure in AngII-dependent hypertensive mice following central administration. Additionally, this study supports the further development of PLL50-PEG CuZnSOD nanozyme as an antioxidant-based therapeutic option for hypertension. PMID:24924945

  9. Hypertension.

    PubMed

    Poulter, Neil R; Prabhakaran, Dorairaj; Caulfield, Mark

    2015-08-22

    Raised blood pressure is the biggest single contributor to the global burden of disease and to global mortality. The numbers of people affected and the prevalence of high blood pressure worldwide are expected to increase over the next decade. Preventive strategies are therefore urgently needed, especially in less developed countries, and management of hypertension must be optimised. Genetic advances in some rare causes of hypertension have been made lately, but the aggregate effect on blood pressure of all the genetic loci identified to date is small. Hence, intervention on key environmental determinants and effective implementation of trial-based therapies are needed. Three-drug combinations can control hypertension in about 90% of patients but only if resources allow identification of patients and drug delivery is affordable. Furthermore, assessment of optimal drug therapy for each ethnic group is needed. PMID:25832858

  10. Renal Deletion of 12 kDa FK506-Binding Protein Attenuates Tacrolimus-Induced Hypertension.

    PubMed

    Lazelle, Rebecca A; McCully, Belinda H; Terker, Andrew S; Himmerkus, Nina; Blankenstein, Katharina I; Mutig, Kerim; Bleich, Markus; Bachmann, Sebastian; Yang, Chao-Ling; Ellison, David H

    2016-05-01

    Tacrolimus is a widely used immunosuppressive drug that inhibits the phosphatase calcineurin when bound to the 12 kDa FK506-binding protein (FKBP12). When this binding occurs in T cells, it leads to immunosuppression. Tacrolimus also causes side effects, however, such as hypertension and hyperkalemia. Previously, we reported that tacrolimus stimulates the renal thiazide-sensitive sodium chloride cotransporter (NCC), which is necessary for the development of hypertension. However, it was unclear if tacrolimus-induced hypertension resulted from tacrolimus effects in renal epithelial cells directly or in extrarenal tissues, and whether inhibition of calcineurin was required. To address these questions, we developed a mouse model in which FKBP12 could be deleted along the nephron. FKBP12 disruption alone did not cause phenotypic effects. When treated with tacrolimus, however, BP and the renal abundance of phosphorylated NCC were lower in mice lacking FKBP12 along the nephron than in control mice. Mice lacking FKBP12 along the nephron also maintained a normal relationship between plasma potassium levels and the abundance of phosphorylated NCC with tacrolimus treatment. In cultured cells, tacrolimus inhibited dephosphorylation of NCC. Together, these results suggest that tacrolimus causes hypertension predominantly by inhibiting calcineurin directly in cells expressing NCC, indicating thiazide diuretics may be particularly effective for lowering BP in tacrolimus-treated patients with hypertension. PMID:26432904

  11. Exogenous administration of thiosulfate, a donor of hydrogen sulfide, attenuates angiotensin II-induced hypertensive heart disease in rats

    PubMed Central

    Snijder, P M; Frenay, A R; de Boer, R A; Pasch, A; Hillebrands, J L; Leuvenink, H G D; van Goor, H

    2015-01-01

    Background and Purpose Hypertension is an important mediator of cardiac damage and remodelling. Hydrogen sulfide (H2S) is an endogenously produced gasotransmitter with cardioprotective properties. However, it is not yet in clinical use. We, therefore, investigated the protective effects of sodium thiosulfate (STS), a clinically applicable H2S donor substance, in angiotensin II (Ang II)-induced hypertensive cardiac disease in rats. Experimental Approach Male Sprague Dawley rats were infused with Ang II (435 ng kg min−1) or saline (control) for 3 weeks via s.c. placed osmotic minipumps. During these 3 weeks, rats received i.p. injections of either STS, NaHS or vehicle (0.9% NaCl). Key Results Compared with controls, Ang II infusion caused an increase in systolic and diastolic BP with associated cardiac damage as evidenced by cardiac hypertrophy, an increase in atrial natriuretic peptide (ANP) mRNA, cardiac fibrosis and increased oxidative stress. Treatment with NaHS and STS prevented the development of hypertension and the increase in ANP mRNA levels. Furthermore, the degree of cardiac hypertrophy, the extent of histological fibrosis in combination with the expression of profibrotic genes and the levels of oxidative stress were all significantly decreased. Conclusions and Implications Ang II-induced hypertensive cardiac disease can be attenuated by treatment with STS and NaHS. Although BP regulation is the most plausible mechanism of cardiac protection, the antifibrotic and antioxidant properties of released sulfide may also contribute to their effects. Our data show that H2S might be a valuable addition to the already existing antihypertensive and cardioprotective therapies. Linked Articles This article is part of a themed section on Pharmacology of the Gasotransmitters. To view the other articles in this section visit http://dx.doi.org/10.1111/bph.2015.172.issue-6 PMID:24962324

  12. Endothelin A Receptor Antagonist, Atrasentan, Attenuates Renal and Cardiac Dysfunction in Dahl Salt-Hypertensive Rats in a Blood Pressure Independent Manner

    PubMed Central

    Samad, Mohammed A.; Kim, Ui Kyoung; Kang, Joshua J.; Ke, Qingen; Kang, Peter M.

    2015-01-01

    Proteinuria is a hallmark of chronic kidney disease (CKD) and cardiovascular disease (CVD), and a good predictor of clinical outcome. Selective endothelin A (ETA) receptor antagonist used with renin-angiotensin system (RAS) inhibitors prevents development of proteinuria in CKD. However, whether the improvement in proteinuria would have beneficial effects on CVD, independent of RAS inhibition, is not well understood. In this study, we investigated whether atrasentan, an ETA receptor antagonist, has renal and cardiovascular effects independent of RAS inhibition. Male Dahl salt sensitive (DSS) rats, at six weeks of age, received water with or without different doses of atrasentan and/or enalapril under high salt (HS) diet or normal diet (ND) for 6 weeks. At the end of 12th week, atrasentan at a moderate dose significantly attenuated proteinuria and serum creatinine without reducing mean arterial pressure (MAP), thereby preventing cardiac hypertrophy and improving cardiac function. ACE inhibitor enalapril at a dose that did not significantly lowered BP, attenuated cardiac hypertrophy while moderately improving cardiac function without reducing proteinuria and serum creatinine level. Nonetheless, combined therapy of atrasentan and enalapril that does not altering BP exerted additional cardioprotective effect. Based on these findings, we conclude that BP independent monotherapy of ETA receptor antagonist attenuates the progression of CKD and significantly mitigates CVD independent of RAS inhibition. PMID:25775254

  13. Endothelin A receptor antagonist, atrasentan, attenuates renal and cardiac dysfunction in Dahl salt-hypertensive rats in a blood pressure independent manner.

    PubMed

    Samad, Mohammed A; Kim, Ui Kyoung; Kang, Joshua J; Ke, Qingen; Kang, Peter M

    2015-01-01

    Proteinuria is a hallmark of chronic kidney disease (CKD) and cardiovascular disease (CVD), and a good predictor of clinical outcome. Selective endothelin A (ETA) receptor antagonist used with renin-angiotensin system (RAS) inhibitors prevents development of proteinuria in CKD. However, whether the improvement in proteinuria would have beneficial effects on CVD, independent of RAS inhibition, is not well understood. In this study, we investigated whether atrasentan, an ETA receptor antagonist, has renal and cardiovascular effects independent of RAS inhibition. Male Dahl salt sensitive (DSS) rats, at six weeks of age, received water with or without different doses of atrasentan and/or enalapril under high salt (HS) diet or normal diet (ND) for 6 weeks. At the end of 12th week, atrasentan at a moderate dose significantly attenuated proteinuria and serum creatinine without reducing mean arterial pressure (MAP), thereby preventing cardiac hypertrophy and improving cardiac function. ACE inhibitor enalapril at a dose that did not significantly lowered BP, attenuated cardiac hypertrophy while moderately improving cardiac function without reducing proteinuria and serum creatinine level. Nonetheless, combined therapy of atrasentan and enalapril that does not altering BP exerted additional cardioprotective effect. Based on these findings, we conclude that BP independent monotherapy of ETA receptor antagonist attenuates the progression of CKD and significantly mitigates CVD independent of RAS inhibition. PMID:25775254

  14. Low carbohydrate/high-fat diet attenuates cardiac hypertrophy, remodeling, and altered gene expression in hypertension

    Technology Transfer Automated Retrieval System (TEKTRAN)

    The effects of dietary fat intake on the development of left ventricular hypertrophy and accompanying structural and molecular remodeling in response to hypertension are not understood. The present study compared the effects of a high-fat versus a low-fat diet on development of left ventricular hype...

  15. Hypothalamic signaling mechanisms in hypertension.

    PubMed

    Carmichael, Casey Y; Wainford, Richard D

    2015-05-01

    The etiology of hypertension, a critical public health issue affecting one in three US adults, involves the integration of the actions of multiple organ systems, including the central nervous system. Increased activation of the central nervous system, driving enhanced sympathetic outflow and increased blood pressure, has emerged as a major contributor to the pathogenesis of hypertension. The hypothalamus is a key brain site acting to integrate central and peripheral inputs to ultimately impact blood pressure in multiple disease states that evoke hypertension. This review highlights recent advances that have identified novel signal transduction mechanisms within multiple hypothalamic nuclei (e.g., paraventricular nucleus, arcuate nucleus) acting to drive the pathophysiology of hypertension in neurogenic hypertension, angiotensin II hypertension, salt-sensitive hypertension, chronic intermittent hypoxia, and obesity-induced hypertension. Increased understanding of hypothalamic activity in hypertension has the potential to identify novel targets for future therapeutic interventions designed to treat hypertension. PMID:25860531

  16. Propylthiouracil Attenuates Experimental Pulmonary Hypertension via Suppression of Pen-2, a Key Component of Gamma-Secretase.

    PubMed

    Lai, Ying-Ju; Chang, Gwo-Jyh; Yeh, Yung-Hsin; Pang, Jong-Hwei S; Huang, Chung-Chi; Chen, Wei-Jan

    2015-01-01

    Gamma-secretase-mediated Notch3 signaling is involved in smooth muscle cell (SMC) hyper-activity and proliferation leading to pulmonary arterial hypertension (PAH). In addition, Propylthiouracil (PTU), beyond its anti-thyroid action, has suppressive effects on atherosclerosis and PAH. Here, we investigated the possible involvement of gamma-secretase-mediated Notch3 signaling in PTU-inhibited PAH. In rats with monocrotaline-induced PAH, PTU therapy improved pulmonary arterial hypertrophy and hemodynamics. In vitro, treatment of PASMCs from monocrotaline-treated rats with PTU inhibited their proliferation and migration. Immunocyto, histochemistry, and western blot showed that PTU treatment attenuated the activation of Notch3 signaling in PASMCs from monocrotaline-treated rats, which was mediated via inhibition of gamma-secretase expression especially its presenilin enhancer 2 (Pen-2) subunit. Furthermore, over-expression of Pen-2 in PASMCs from control rats increased the capacity of migration, whereas knockdown of Pen-2 with its respective siRNA in PASMCs from monocrotaline-treated rats had an opposite effect. Transfection of PASMCs from monocrotaline-treated rats with Pen-2 siRNA blocked the inhibitory effect of PTU on PASMC proliferation and migration, reflecting the crucial role of Pen-2 in PTU effect. We present a novel cell-signaling paradigm in which overexpression of Pen-2 is essential for experimental pulmonary arterial hypertension to promote motility and growth of smooth muscle cells. Propylthiouracil attenuates experimental PAH via suppression of the gamma-secretase-mediated Notch3 signaling especially its presenilin enhancer 2 (Pen-2) subunit. These findings provide a deep insight into the pathogenesis of PAH and a novel therapeutic strategy. PMID:26367462

  17. Dietary N,N-dimethylglycine supplementation improves nutrient digestibility and attenuates pulmonary hypertension syndrome in broilers.

    PubMed

    Kalmar, I D; Cools, A; Buyse, J; Roose, P; Janssens, G P J

    2010-12-01

    N,N-dimethylglycine (DMG) is an intermediary metabolite in cellular choline and betaine metabolism. The present trial aimed to evaluate the effect of dietary DMG on nutrient digestibility and development of pulmonary hypertension syndrome in broilers. A total of 64 14-day-old broiler hens (Ross-308) were raised until age 40 days under cold environmental temperature conditions (15 °C) and were fed a high energy feed in order to incite pulmonary hypertension. Birds were randomly assigned to two groups of which each group had eight replicate pens of four birds each. Test diets contained 0 or 167 mg Na-DMG (Taminizer(®) D; Taminco N.V., Ghent, Belgium)/kg feed. N,N-dimethylglycine supplementation resulted in a significant improvement in apparent faecal digestibility of crude protein and nitrogen-free extract. Further, fulminant ascites was numerically lowered by DMG and incidence of pulmonary hypertension decreased significantly from 44.8% in the control group to 14.6% in the DMG group. Finally, fasted plasma level of non-esterified fatty acids (NEFA) was twofold in the control group in relation to the DMG group. In conclusion, these data demonstrate beneficial effects of DMG on digestibility of non-fat fractions, on fat metabolism and on progression towards broiler ascites syndrome. PMID:20662970

  18. Nitrooleic Acid Attenuates Lipid Metabolic Disorders and Liver Steatosis in DOCA-Salt Hypertensive Mice

    PubMed Central

    Sun, Jing; Jia, Zhanjun; Yang, Tianxin; Xu, Liang; Zhao, Bing; Yu, Kezhou; Wang, Rong

    2015-01-01

    Nitrooleic acid (OA-NO2) is endogenous ligands for peroxisome proliferator-activated receptors. The present study was aimed at investigating the beneficial effects of OA-NO2 on the lipid metabolism and liver steatosis in deoxycorticosterone acetate- (DOCA-) salt induced hypertensive mice model. Male C57BL/6 mice were divided to receive DOCA-salt plus OA-NO2 or DOCA-salt plus vehicle and another group received neither DOCA-salt nor OA-NO2 (control group). After 3-week treatment with DOCA-salt plus 1% sodium chloride in drinking fluid, the hypertension was noted; however, OA-NO2 had no effect on the hypertension. In DOCA-salt treated mice, the plasma triglyceride and total cholesterol levels were significantly increased compared to control mice, and pretreatment with OA-NO2 significantly reduced these parameters. Further, the histopathology of liver exhibited more lipid distribution together with more serious micro- and macrovesicular steatosis after DOCA-salt treatment and that was consistent with liver tissue triglyceride and nonesterified fatty acids (NEFA) content. The mice pretreated with OA-NO2 showed reduced liver damage accompanied with low liver lipid content. Moreover, the liver TBARS, together with the expressions of gp91phox and p47phox, were parallelly decreased. These findings indicated that OA-NO2 had the protective effect on liver injury against DOCA-salt administration and the beneficial effect could be attributed to its antihyperlipidemic activities. PMID:25861250

  19. Activation of Central PPAR-γ Attenuates Angiotensin II-Induced Hypertension

    PubMed Central

    Yu, Yang; Xue, Bao-Jian; Wei, Shun-Guang; Zhang, Zhi-Hua; Beltz, Terry G; Guo, Fang; Johnson, Alan Kim; Felder, Robert B

    2015-01-01

    Inflammation and renin-angiotensin system activity in the brain contribute to hypertension through effects on fluid intake, vasopressin release, and sympathetic nerve activity. We recently reported that activation of brain peroxisome proliferator-activated receptor (PPAR)-γ in heart failure rats reduced inflammation and renin-angiotensin system activity in the hypothalamic paraventricular nucleus and ameliorated the peripheral manifestations of heart failure. We hypothesized that activation of brain PPAR-γ might have beneficial effects in angiotensin II-induced hypertension. Sprague-Dawley rats received a 2-week subcutaneous infusion of angiotensin II (120 ng/kg/min) combined with a continuous intracerebroventricular infusion of vehicle, the PPAR-γ agonist pioglitazone (3 nmol/h) or the PPAR-γ antagonist GW9662 (7 nmol/h). Angiotensin II+vehicle rats had increased mean blood pressure, increased sympathetic drive as indicated by the mean blood pressure response to ganglionic blockade, and increased water consumption. PPAR-γ mRNA in subfornical organ and hypothalamic paraventricular nucleus was unchanged, but PPAR-γ DNA binding activity was reduced. mRNA for interleukin-1β, tumor necrosis factor-α, cyclooxygenase-2 and angiotensin II type-1 receptor was augmented in both nuclei, and hypothalamic paraventricular nucleus neuronal activity was increased. The plasma vasopressin response to a 6-hour water restriction also increased. These responses to angiotensin II were exacerbated by GW9662 and ameliorated by pioglitazone, which increased PPAR-γ mRNA and PPAR-γ DNA binding activity in subfornical organ and hypothalamic paraventricular nucleus. Pioglitazone and GW9662 had no effects on control rats. The results suggest that activating brain PPAR-γ to reduce central inflammation and brain renin-angiotensin system activity may be a useful adjunct in the treatment of angiotensin II-dependent hypertension. PMID:26101342

  20. Activation of central PPAR-γ attenuates angiotensin II-induced hypertension.

    PubMed

    Yu, Yang; Xue, Bao-Jian; Wei, Shun-Guang; Zhang, Zhi-Hua; Beltz, Terry G; Guo, Fang; Johnson, Alan Kim; Felder, Robert B

    2015-08-01

    Inflammation and renin-angiotensin system activity in the brain contribute to hypertension through effects on fluid intake, vasopressin release, and sympathetic nerve activity. We recently reported that activation of brain peroxisome proliferator-activated receptor (PPAR)-γ in heart failure rats reduced inflammation and renin-angiotensin system activity in the hypothalamic paraventricular nucleus and ameliorated the peripheral manifestations of heart failure. We hypothesized that the activation of brain PPAR-γ might have beneficial effects in angiotensin II-induced hypertension. Sprague-Dawley rats received a 2-week subcutaneous infusion of angiotensin II (120 ng/kg per minute) combined with a continuous intracerebroventricular infusion of vehicle, the PPAR-γ agonist pioglitazone (3 nmol/h) or the PPAR-γ antagonist GW9662 (7 nmol/h). Angiotensin II+vehicle rats had increased mean blood pressure, increased sympathetic drive as indicated by the mean blood pressure response to ganglionic blockade, and increased water consumption. PPAR-γ mRNA in subfornical organ and hypothalamic paraventricular nucleus was unchanged, but PPAR-γ DNA-binding activity was reduced. mRNA for interleukin-1β, tumor necrosis factor-α, cyclooxygenase-2, and angiotensin II type 1 receptor was augmented in both nuclei, and hypothalamic paraventricular nucleus neuronal activity was increased. The plasma vasopressin response to a 6-hour water restriction also increased. These responses to angiotensin II were exacerbated by GW9662 and ameliorated by pioglitazone, which increased PPAR-γ mRNA and PPAR-γ DNA-binding activity in subfornical organ and hypothalamic paraventricular nucleus. Pioglitazone and GW9662 had no effects on control rats. The results suggest that activating brain PPAR-γ to reduce central inflammation and brain renin-angiotensin system activity may be a useful adjunct in the treatment of angiotensin II-dependent hypertension. PMID:26101342

  1. Quantitative proteomics reveals novel therapeutic and diagnostic markers in hypertension.

    PubMed

    Matafora, Vittoria; Zagato, Laura; Ferrandi, Mara; Molinari, Isabella; Zerbini, Gianpaolo; Casamassima, Nunzia; Lanzani, Chiara; Delli Carpini, Simona; Trepiccione, Francesco; Manunta, Paolo; Bachi, Angela; Capasso, Giovambattista

    2014-12-01

    Hypertension is a prevalent disorder in the world representing one of the major risk factors for heart attack and stroke. These risks are increased in salt sensitive individuals. Hypertension and salt sensitivity are complex phenotypes whose pathophysiology remains poorly understood and, remarkably, salt sensitivity is still laborious to diagnose. Here we present a urinary proteomic study specifically designed to identify urinary proteins relevant for the pathogenesis of hypertension and salt sensitivity. Despite previous studies that underlined the association of UMOD gene variants with hypertension, this work provides novel evidence showing different uromodulin protein level in the urine of hypertensive patients compared to healthy individuals. Notably, we also show that patients with higher level of uromodulin are homozygous for UMOD risk variant and display a decreased level of salt excretion, highlighting the essential role of UMOD in the regulation of salt reabsorption in hypertension. Additionally, we found that urinary nephrin 1, a marker of glomerular slit diaphragm, may predict a salt sensitive phenotype and positively correlate with increased albuminuria associated with this type of hypertension. PMID:26672470

  2. Chronic infusion of enalaprilat into hypothalamic paraventricular nucleus attenuates angiotensin II-induced hypertension and cardiac hypertrophy by restoring neurotransmitters and cytokines

    SciTech Connect

    Kang, Yu-Ming; Zhang, Dong-Mei; Yu, Xiao-Jing; Yang, Qing; Qi, Jie; Su, Qing; Suo, Yu-Ping; Yue, Li-Ying; Zhu, Guo-Qing; Qin, Da-Nian

    2014-02-01

    The renin–angiotensin system (RAS) in the brain is involved in the pathogenesis of hypertension. We hypothesized that inhibition of angiotensin-converting enzyme (ACE) in the hypothalamic paraventricular nucleus (PVN) attenuates angiotensin II (ANG II)-induced hypertension via restoring neurotransmitters and cytokines. Rats underwent subcutaneous infusions of ANG II or saline and bilateral PVN infusions of ACE inhibitor enalaprilat (ENL, 2.5 μg/h) or vehicle for 4 weeks. ANG II infusion resulted in higher mean arterial pressure and cardiac hypertrophy as indicated by increased whole heart weight/body weight ratio, whole heart weight/tibia length ratio, left ventricular weight/tibia length ratio, and mRNA expressions of cardiac atrial natriuretic peptide and beta-myosin heavy chain. These ANG II-infused rats had higher PVN levels of glutamate, norepinephrine, tyrosine hydroxylase, pro-inflammatory cytokines (PICs) and the chemokine monocyte chemoattractant protein-1, and lower PVN levels of gamma-aminobutyric acid, interleukin (IL)-10 and the 67-kDa isoform of glutamate decarboxylase (GAD67), and higher plasma levels of PICs, norepinephrine and aldosterone, and lower plasma IL-10, and higher renal sympathetic nerve activity. However, PVN treatment with ENL attenuated these changes. PVN microinjection of ANG II induced increases in IL-1β and IL-6, and a decrease in IL-10 in the PVN, and pretreatment with angiotensin II type 1 receptor (AT1-R) antagonist losartan attenuated these changes. These findings suggest that ANG II infusion induces an imbalance between excitatory and inhibitory neurotransmitters and an imbalance between pro- and anti-inflammatory cytokines in the PVN, and PVN inhibition of the RAS restores neurotransmitters and cytokines in the PVN, thereby attenuating ANG II-induced hypertension and cardiac hypertrophy. - Highlights: • Chronic ANG II infusion results in sympathetic hyperactivity and cardiac hypertrophy. • PVN inhibition of ACE

  3. Effects of salt intake and potassium supplementation on renalase expression in the kidneys of Dahl salt-sensitive rats.

    PubMed

    Zheng, Wen-Ling; Wang, Jing; Mu, Jian-Jun; Liu, Fu-Qiang; Yuan, Zu-Yi; Wang, Yang; Wang, Dan; Ren, Ke-Yu; Guo, Tong-Shuai; Xiao, Hong-Yu

    2016-02-01

    Renalase is currently the only known amine oxidase in the blood that can metabolize catecholamines and regulate sympathetic activity. High salt intake is associated with high blood pressure (BP), possibly through the modulation of renalase expression and secretion, whereas potassium can reverse the high salt-mediated increase in blood pressure. However, whether potassium could also modulate BP through renalase is unclear. In this study, we aim to investigate how salt intake and potassium supplementation affect the level of renalase in rats. Eighteen salt-sensitive (SS) and 18 SS-13BN rats were divided into six groups, receiving normal salt (0.3% NaCl), high salt (8% NaCl) and high salt/potassium (8% NaCl and 8% KCl) dietary intervention for four weeks. At the end of experiments, blood and kidneys were collected for analysis. mRNA level of renalase was measured by quantitative real-time PCR and protein level was determined by Western blot. We found that mRNA and protein levels of renalase in the kidneys of SS and SS-13BN rats were significantly decreased (P < 0.05) after high salt intervention, whereas dopamine in plasma was increased (P < 0.05) compared with rats received normal salt, suggesting that salt may induce salt-sensitive hypertension through inhibition of renalase expression. We also found increased mRNA level and protein level of renalase, decreased catecholamine levels in plasma, and decreased BP in SS rats treated with high salt/potassium, compared with that of the high salt SS group. Taken together, the salt-induced increase and potassium-induced decrease in BP could be mediated through renalase. More studies are needed to confirm our findings and understand the underlying mechanisms. PMID:26553126

  4. Sodium nitrite attenuates hypertension-in-pregnancy and blunts increases in soluble fms-like tyrosine kinase-1 and in vascular endothelial growth factor.

    PubMed

    Gonçalves-Rizzi, Victor Hugo; Possomato-Vieira, Jose Sergio; Sales Graça, Tamiris Uracs; Nascimento, Regina Aparecida; Dias-Junior, Carlos A

    2016-07-01

    Preeclampsia is a pregnancy-associated disorder characterized by hypertension with uncertain pathogenesis. Increases in antiangiogenic soluble fms-like tyrosine kinase-1 (sFlt-1) and reductions in nitric oxide (NO) bioavailability have been observed in preeclamptic women. However, the specific mechanisms linking these detrimental changes to the hypertension-in-pregnancy are not clearly understood. In this regard, while recent findings have suggested that nitrite-derived NO formation exerts antihypertensive and antioxidant effects, no previous study has examined these responses to orally administered nitrite in hypertension-in-pregnancy. We then hypothesized restoring NO bioavailability with sodium nitrite in pregnant rats upon NO synthesis inhibition with N(omega)-nitro-l-arginine methyl ester (L-NAME) attenuates hypertension and high circulating levels of sFlt-1. Number and weight of pups and placentae were recorded to assess maternal-fetal interface. Plasma sFlt-1, vascular endothelial growth factor (VEGF) and biochemical determinants of NO formation and of antioxidant function were measured. We found that sodium nitrite blunts the hypertension-in-pregnancy and restores the NO bioavailability, and concomitantly prevents the L-NAME-induced high circulating sFlt-1 and VEGF levels. Also, our results suggest that nitrite-derived NO protected against reductions in litter size and placental weight caused by L-NAME, improving number of viable and resorbed fetuses and antioxidant function. Therefore, the present findings are consistent with the hypothesis that nitrite-derived NO may possibly be the driving force behind the maternal and fetal beneficial effects observed with sodium nitrite during hypertension-in-pregnancy. Certainly further investigations are required in preeclampsia, since counteracting the damages to the mother and fetal sides resulting from hypertension and elevated sFlt-1 levels may provide a great benefit in this gestational hypertensive disease

  5. Melatonin attenuates hypertension-related proarrhythmic myocardial maladaptation of connexin-43 and propensity of the heart to lethal arrhythmias.

    PubMed

    Benova, Tamara; Viczenczova, Csilla; Radosinska, Jana; Bacova, Barbara; Knezl, Vladimir; Dosenko, Victor; Weismann, Peter; Zeman, Michal; Navarova, Jana; Tribulova, Narcis

    2013-08-01

    We hypothesized that the pineal hormone melatonin, which exhibits cardioprotective effects, might affect myocardial expression of cell-to-cell electrical coupling protein connexin-43 (Cx43) and protein kinase C (PKC) signaling, and hence, the propensity of the heart to lethal ventricular fibrillation (VF). Spontaneously hypertensive (SHR) and normotensive Wistar rats fed a standard rat chow received melatonin (40 μg/mL in drinking water during the night) for 5 weeks, and were compared with untreated rats. Melatonin significantly reduced blood pressure and normalized triglycerides in SHR, whereas it decreased body mass and adiposity in Wistar rats. Compared with healthy rats, the threshold to induce sustained VF was significantly lower in SHR (18.3 ± 2.6 compared with 29.2 ± 5 mA; p < 0.05) and increased in melatonin-treated SHR and Wistar rats to 33.0 ± 4 and 32.5 ± 4 mA. Melatonin attenuated abnormal myocardial Cx43 distribution in SHR, and upregulated Cx43 mRNA, total Cx43 protein, and its functional phosphorylated forms in SHR, and to a lesser extent, in Wistar rat hearts. Moreover, melatonin suppressed myocardial proapoptotic PKCδ expression and increased cardioprotective PKCε expression in both SHR and Wistar rats. Our findings indicate that melatonin protects against lethal arrhythmias at least in part via upregulation of myocardial Cx43 and modulation of PKC-related cardioprotective signaling. PMID:23889002

  6. Netrin-1 rescues neuron loss by attenuating secondary apoptosis in ipsilateral thalamic nucleus following focal cerebral infarction in hypertensive rats.

    PubMed

    Liao, S-J; Gong, Q; Chen, X-R; Ye, L-X; Ding, Q; Zeng, J-S; Yu, J

    2013-02-12

    Neurological deficit following cerebral infarction correlates with not only primary injury, but also secondary neuronal apoptosis in remote loci connected to the infarction. Netrin-1 is crucial for axonal guidance by interacting with its receptors, deleted in colorectal cancer (DCC) and uncoordinated gene 5H (UNC5H). DCC and UNC5H are also dependence receptors inducing cell apoptosis when unbound by netrin-1. The present study is to investigate the role of netrin-1 and its receptors in ipsilateral ventroposterior thalamic nucleus (VPN) injury secondary to stroke in hypertensive rats. Renovascular hypertensive Sprague-Dawley rats underwent middle cerebral artery occlusion (MCAO). Continuous intracerebroventricular infusion of netrin-1 (600 ng/d for 7 days) or vehicle (IgG/Fc) was given 24h after MCAO. Neurological function was evaluated by postural reflex 8 and 14 days after MCAO. Then, immunoreactivity was determined in the ipsilateral VPN for NeuN, glial fibrillary acidic protein, netrin-1 and its receptors (DCC and UNC5H2), apoptosis was detected with Terminal deoxynucleotidyl transferase-mediated digoxigenin-dUTP-biotin nick-end labeling (TUNEL) assay, and the expressions of caspase-3, netrin-1, DCC, and UNC5H2 were quantified by western blot analysis. MCAO resulted in the impaired postural reflex after 8 and 14 days, with decreased NeuN marked neurons and increased TUNEL-positive cells, as well as an up-regulation in the levels of cleaved caspase-3 and UNC5H2 protein in the ipsilateral VPN, without significant change in DCC or netrin-1 expression. By exogenous netrin-1 infusion, the number of neurons was increased in the ipsilateral VPN, and both TUNEL-positive cell number and caspase-3 protein level were reduced, while UNC5H2 expression remained unaffected, simultaneously, the impairment of postural reflex was improved. Taken together, the present study indicates that exogenous netrin-1 could rescue neuron loss by attenuating secondary apoptosis in the

  7. The Role of Aldosterone in Obesity-Related Hypertension.

    PubMed

    Kawarazaki, Wakako; Fujita, Toshiro

    2016-04-01

    Obese subjects often have hypertension and related cardiovascular and renal diseases, and this has become a serious worldwide health problem. In obese subjects, impaired renal-pressure natriuresis causes sodium retention, leading to the development of salt-sensitive hypertension. Physical compression of the kidneys by visceral fat and activation of the sympathetic nervous system, renin-angiotensin systems (RAS), and aldosterone/mineralocorticoid receptor (MR) system are involved in this mechanism. Obese subjects often exhibit hyperaldosteronism, with increased salt sensitivity of blood pressure (BP). Adipose tissue excretes aldosterone-releasing factors, thereby stimulating aldosterone secretion independently of the systemic RAS, and aldosterone/MR activation plays a key role in the development of hypertension and organ damage in obesity. In obese subjects, both salt sensitivity of BP, enhanced by obesity-related metabolic disorders including aldosterone excess, and increased dietary sodium intake are closely related to the incidence of hypertension. Some salt sensitivity-related gene variants affect the risk of obesity, and together with salt intake, its combination is possibly associated with the development of hypertension in obese subjects. With high salt levels common in modern diets, salt restriction and weight control are undoubtedly important. However, not only MR blockade but also new diagnostic modalities and therapies targeting and modifying genes that are related to salt sensitivity, obesity, or RAS regulation are expected to prevent obesity and obesity-related hypertension. PMID:26927805

  8. Chronic Activation of Heme Free Guanylate Cyclase Leads to Renal Protection in Dahl Salt-Sensitive Rats.

    PubMed

    Hoffmann, Linda S; Kretschmer, Axel; Lawrenz, Bettina; Hocher, Berthold; Stasch, Johannes-Peter

    2015-01-01

    The nitric oxide (NO)/soluble guanylate cyclase (sGC)/cyclic guanosine monophasphate (cGMP)-signalling pathway is impaired under oxidative stress conditions due to oxidation and subsequent loss of the prosthetic sGC heme group as observed in particular in chronic renal failure. Thus, the pool of heme free sGC is increased under pathological conditions. sGC activators such as cinaciguat selectively activate the heme free form of sGC and target the disease associated enzyme. In this study, a therapeutic effect of long-term activation of heme free sGC by the sGC activator cinaciguat was investigated in an experimental model of salt-sensitive hypertension, a condition that is associated with increased oxidative stress, heme loss from sGC and development of chronic renal failure. For that purpose Dahl/ss rats, which develop severe hypertension upon high salt intake, were fed a high salt diet (8% NaCl) containing either placebo or cinaciguat for 21 weeks. Cinaciguat markedly improved survival and ameliorated the salt-induced increase in blood pressure upon treatment with cinaciguat compared to placebo. Renal function was significantly improved in the cinaciguat group compared to the placebo group as indicated by a significantly improved glomerular filtration rate and reduced urinary protein excretion. This was due to anti-fibrotic and anti-inflammatory effects of the cinaciguat treatment. Taken together, this is the first study showing that long-term activation of heme free sGC leads to renal protection in an experimental model of hypertension and chronic kidney disease. These results underline the promising potential of cinaciguat to treat renal diseases by targeting the disease associated heme free form of sGC. PMID:26717150

  9. Chronic Activation of Heme Free Guanylate Cyclase Leads to Renal Protection in Dahl Salt-Sensitive Rats

    PubMed Central

    Hoffmann, Linda S.; Kretschmer, Axel; Lawrenz, Bettina; Hocher, Berthold; Stasch, Johannes-Peter

    2015-01-01

    The nitric oxide (NO)/soluble guanylate cyclase (sGC)/cyclic guanosine monophasphate (cGMP)-signalling pathway is impaired under oxidative stress conditions due to oxidation and subsequent loss of the prosthetic sGC heme group as observed in particular in chronic renal failure. Thus, the pool of heme free sGC is increased under pathological conditions. sGC activators such as cinaciguat selectively activate the heme free form of sGC and target the disease associated enzyme. In this study, a therapeutic effect of long-term activation of heme free sGC by the sGC activator cinaciguat was investigated in an experimental model of salt-sensitive hypertension, a condition that is associated with increased oxidative stress, heme loss from sGC and development of chronic renal failure. For that purpose Dahl/ss rats, which develop severe hypertension upon high salt intake, were fed a high salt diet (8% NaCl) containing either placebo or cinaciguat for 21 weeks. Cinaciguat markedly improved survival and ameliorated the salt-induced increase in blood pressure upon treatment with cinaciguat compared to placebo. Renal function was significantly improved in the cinaciguat group compared to the placebo group as indicated by a significantly improved glomerular filtration rate and reduced urinary protein excretion. This was due to anti-fibrotic and anti-inflammatory effects of the cinaciguat treatment. Taken together, this is the first study showing that long-term activation of heme free sGC leads to renal protection in an experimental model of hypertension and chronic kidney disease. These results underline the promising potential of cinaciguat to treat renal diseases by targeting the disease associated heme free form of sGC. PMID:26717150

  10. Ebselen attenuates oxidative DNA damage and enhances its repair activity in the thalamus after focal cortical infarction in hypertensive rats.

    PubMed

    He, Meixia; Xing, Shihui; Yang, Bo; Zhao, Liqun; Hua, Haiying; Liang, Zhijian; Zhou, Wenliang; Zeng, Jinsheng; Pei, Zhong

    2007-11-21

    Oxidative DNA damage has been proposed to be a major contributor to focal cerebral ischemic injury. However, little is known about the role of oxidative DNA damage in remote damage secondary to the primary infarction. In the present study, we investigated oxidative damage within the ventroposterior nucleus (VPN) after distal middle cerebral artery occlusion (MCAO) in hypertensive rats. We also examined the possible protective effect of ebselen, one glutathione peroxidase mimic, on delayed degeneration in the VPN after distal MCAO. Neuronal damage in the ipsilateral VPN was examined by Nissl staining. Oxidative DNA damage and base repair enzyme activity were assessed by analyzing immunoreactivity of 8-hydroxy-2'-deoxyguanosine (8-ohdG) and 8-oxoguanine DNA glycosylase (OGG1), respectively. The number of intact neurons in the ipsilateral VPN decreased by 52% compared to the contralateral side in ischemia group 2 weeks after distal cerebral cortical infarction. The immunoreactivity of 8-ohdG significantly increased while OGG1 immunoreactivity significantly decreased in the ipsilateral VPN 2 weeks after distal cortical infarction (all p<0.01). Compared with vehicle treatment, ebselen significantly attenuated the neuron loss, ameliorated ischemia-induced increase in 8-ohdG level as well as decrease in OGG1 level within the ipsilateral VPN (all p<0.01). OGG1 was further demonstrated to mainly express in neurons. These findings strongly suggest that oxidative DNA damage may be involved in the delayed neuronal death in the VPN region following distal MCAO. Furthermore, ebselen protects against the delayed damage in the VPN when given at 24 h following distal MCAO. PMID:17920569

  11. Mizoribine Ameliorates Renal Injury and Hypertension along with the Attenuation of Renal Caspase-1 Expression in Aldosterone-Salt-Treated Rats

    PubMed Central

    Doi, Toshiki; Doi, Shigehiro; Nakashima, Ayumu; Ueno, Toshinori; Yokoyama, Yukio; Kohno, Nobuoki; Masaki, Takao

    2014-01-01

    Aldosterone-salt treatment induces not only hypertension but also extensive inflammation that contributes to fibrosis in the rat kidney. However, the mechanism underlying aldosterone-salt-induced renal inflammation remains unclear. Pyroptosis has recently been identified as a new type of cell death that is accompanied by the activation of inflammatory cytokines. We hypothesized that aldosterone-salt treatment could induce inflammation through pyroptosis and that mizoribine, an effective immunosuppressant, would ameliorate the renal inflammation that would otherwise cause renal fibrosis. Ten days after recovery from left uninephrectomy, rats were given drinking water with 1% sodium chloride. The animals were divided into three groups (n = 7 per group): (1) vehicle infusion group, (2) aldosterone infusion group, or (3) aldosterone infusion plus oral mizoribine group. Aldosterone-salt treatment increased the expression of the nucleotide-binding oligomerization domain, leucine-rich repeat and pyrin domain containing 3 and caspase-1, and also increased the number of terminal deoxynucleotidyl transferase dUTP nick end labeling-positive cells. However, the oral administration of mizoribine attenuated these alterations. Furthermore, mizoribine inhibited hypertension and renal fibrosis, and also attenuated the aldosterone-induced expression of serum/glucocorticoid-regulated kinase and α epithelial sodium channel. These results suggest that caspase-1 activation plays an important role in the development of inflammation induced by aldosterone-salt treatment and that it functions as an anti-inflammatory strategy that protects against renal injury and hypertension. PMID:24695748

  12. Angiotensin II-Induced Hypertension Is Attenuated by Overexpressing Copper/Zinc Superoxide Dismutase in the Brain Organum Vasculosum of the Lamina Terminalis

    PubMed Central

    Collister, John P.; Taylor-Smith, Heather; Drebes, Donna; Nahey, David; Tian, Jun; Zimmerman, Matthew C.

    2016-01-01

    Angiotensin II (AngII) can access the brain via circumventricular organs (CVOs), including the subfornical organ (SFO) and organum vasculosum of the lamina terminalis (OVLT), to modulate blood pressure. Previous studies have demonstrated a role for both the SFO and OVLT in the hypertensive response to chronic AngII, yet it is unclear which intracellular signaling pathways are involved in this response. Overexpression of copper/zinc superoxide dismutase (CuZnSOD) in the SFO has been shown to attenuate the chronic hypertensive effects of AngII. Presently, we tested the hypothesis that elevated levels of superoxide (O2∙−) in the OVLT contribute to the hypertensive effects of AngII. To facilitate overexpression of superoxide dismutase, adenoviral vectors encoding human CuZnSOD or control adenovirus (AdEmpty) were injected directly into the OVLT of rats. Following 3 days of control saline infusion, rats were intravenously infused with AngII (10 ng/kg/min) for ten days. Blood pressure increased 33 ± 8 mmHg in AdEmpty rats (n = 6), while rats overexpressing CuZnSOD (n = 8) in the OVLT demonstrated a blood pressure increase of only 18 ± 5 mmHg after 10 days of AngII infusion. These results support the hypothesis that overproduction of O2∙− in the OVLT plays an important role in the development of chronic AngII-dependent hypertension. PMID:26881025

  13. Central Infusion of Angiotensin II Type 2 Receptor Agonist Compound 21 Attenuates DOCA/NaCl-Induced Hypertension in Female Rats

    PubMed Central

    Dai, Shu-Yan; Zhang, Yu-Ping; Peng, Wei; Shen, Ying; He, Jing-Jing

    2016-01-01

    The present study investigated whether central activation of angiotensin II type 2 receptor (AT2-R) attenuates deoxycorticosterone acetate (DOCA)/NaCl-induced hypertension in intact and ovariectomized (OVX) female rats and whether female sex hormone status has influence on the effects of AT2-R activation. DOCA/NaCl elicited a greater increase in blood pressure in OVX females than that in intact females. Central infusion of compound 21, a specific AT2-R agonist, abolished DOCA/NaCl pressor effect in intact females, whereas same treatment in OVX females produced an inhibitory effect. Real-time RT-PCR analysis revealed that DOCA/NaCl enhanced the mRNA expression of hypertensive components including AT1-R, ACE-1, and TNF-α in the paraventricular nucleus of hypothalamus in both intact and OVX females. However, the mRNA expressions of antihypertensive components such as AT2-R, ACE-2, and IL-10 were increased only in intact females. Central AT2-R agonist reversed the changes in the hypertensive components in all females, while this agonist further upregulated the expression of ACE2 and IL-10 in intact females, but only IL-10 in OVX females. These results indicate that brain AT2-R activation plays an inhibitory role in the development of DOCA/NaCl-induced hypertension in females. This beneficial effect of AT2-R activation involves regulation of renin-angiotensin system and proinflammatory cytokines. PMID:26783414

  14. The response of Dahl salt-sensitive and salt-resistant female rats to a space flight model

    NASA Technical Reports Server (NTRS)

    Thierry-Palmer, Myrtle; Cephas, Stacy; Cleek, Tammy; Sayavongsa, Phouyong; Arnaud, Sara B.

    2003-01-01

    Vitamin D metabolism in the Dahl salt-sensitive (S) rat, a model of salt-induced hypertension, differs from that in the Dahl salt-resistant (R) rat. We have tested the hypothesis that differences in vitamin D metabolism would render the Dahl S rat more susceptible than the Dahl R rat to the effects of a space flight model. Dahl female rats were tail suspended (hind limb unloaded) for 28 days, while fed a low salt (3 g/kg sodium chloride) diet. Plasma 25-OHD concentrations of S rats were significantly lower than that of R rats. Plasma 1,25-(OH)2D concentration was 50% lower in unloaded than in loaded S rats, but was unaffected in unloaded R rats. The left soleus muscle weight and breaking strength of the left femur (torsion test) were 50% and 25% lower in unloaded than in loaded S and R rats. The mineral content of the left femur, however, was significantly lower (by 11%) only in unloaded S rats. We conclude that female S rats are more vulnerable than female R rats to decreases in plasma 1,25-(OH)2D concentration and femur mineral content during hind limb unloading, but equally vulnerable to muscle atrophy and reduced breaking strength of the femur.

  15. Oral CoQ10 attenuates high salt-induced hypertension by restoring neurotransmitters and cytokines in the hypothalamic paraventricular nucleus.

    PubMed

    Gao, Hong-Li; Yu, Xiao-Jing; Qi, Jie; Yi, Qiu-Yue; Jing, Wang-Hui; Sun, Wen-Yan; Cui, Wei; Mu, Jian-Jun; Yuan, Zu-Yi; Zhao, Xiu-Fang; Liu, Kai-Li; Zhu, Guo-Qing; Shi, Xiao-Lian; Liu, Jin-Jun; Kang, Yu-Ming

    2016-01-01

    High salt intake leads to an increase in some proinflammatory cytokines and neurotransmitters involved in the pathogenesis of hypertension. The purpose of this work was to know if oral administration of anti-oxidant and free-radical scavenger CoQ10 may attenuate high salt-induced hypertension via regulating neurotransmitters and cytokines in the hypothalamic paraventricular nucleus (PVN). Adult male Sprague-Dawley (SD) rats were fed with a normal salt diet (NS, 0.3% NaCl) or a high salt diet (HS, 8% NaCl) for 15 weeks to induce hypertension. These rats received CoQ10 (10 mg/kg/day) dissolved in olive oil was given by gavage (10 mg/kg/day) for 15 weeks. HS resulted in higher mean arterial pressure (MAP) and the sympathetic nerve activity (RSNA). These HS rats had higher PVN levels of norepinephrine (NE), tyrosine hydroxylase (TH), interleukin (IL)-1β, NOX2 and NOX4, lower PVN levels of gamma-aminobutyric acid (GABA), IL-10, copper/zinc superoxide dismutase (Cu/Zn-SOD) and the 67-kDa isoform of glutamate decarboxylase (GAD67), as compared with NS group. CoQ10 supplementation reduced NE, TH, IL-1β, NOX2 and NOX4 in the PVN, and induced IL-10, Cu/Zn-SOD and GAD67 in the PVN. These findings suggest that CoQ10 supplementation restores neurotransmitters and cytokines in the PVN, thereby attenuating high salt-induced hypertension. PMID:27452860

  16. Oral CoQ10 attenuates high salt-induced hypertension by restoring neurotransmitters and cytokines in the hypothalamic paraventricular nucleus

    PubMed Central

    Gao, Hong-Li; Yu, Xiao-Jing; Qi, Jie; Yi, Qiu-Yue; Jing, Wang-Hui; Sun, Wen-Yan; Cui, Wei; Mu, Jian-Jun; Yuan, Zu-Yi; Zhao, Xiu-Fang; Liu, Kai-Li; Zhu, Guo-Qing; Shi, Xiao-Lian; Liu, Jin-Jun; Kang, Yu-Ming

    2016-01-01

    High salt intake leads to an increase in some proinflammatory cytokines and neurotransmitters involved in the pathogenesis of hypertension. The purpose of this work was to know if oral administration of anti-oxidant and free-radical scavenger CoQ10 may attenuate high salt-induced hypertension via regulating neurotransmitters and cytokines in the hypothalamic paraventricular nucleus (PVN). Adult male Sprague-Dawley (SD) rats were fed with a normal salt diet (NS, 0.3% NaCl) or a high salt diet (HS, 8% NaCl) for 15 weeks to induce hypertension. These rats received CoQ10 (10 mg/kg/day) dissolved in olive oil was given by gavage (10 mg/kg/day) for 15 weeks. HS resulted in higher mean arterial pressure (MAP) and the sympathetic nerve activity (RSNA). These HS rats had higher PVN levels of norepinephrine (NE), tyrosine hydroxylase (TH), interleukin (IL)-1β, NOX2 and NOX4, lower PVN levels of gamma-aminobutyric acid (GABA), IL-10, copper/zinc superoxide dismutase (Cu/Zn-SOD) and the 67-kDa isoform of glutamate decarboxylase (GAD67), as compared with NS group. CoQ10 supplementation reduced NE, TH, IL-1β, NOX2 and NOX4 in the PVN, and induced IL-10, Cu/Zn-SOD and GAD67 in the PVN. These findings suggest that CoQ10 supplementation restores neurotransmitters and cytokines in the PVN, thereby attenuating high salt-induced hypertension. PMID:27452860

  17. Administration of antioxidant peptide SS-31 attenuates transverse aortic constriction-induced pulmonary arterial hypertension in mice

    PubMed Central

    Lu, Hung-i; Huang, Tien-hung; Sung, Pei-hsun; Chen, Yung-lung; Chua, Sarah; Chai, Han-yan; Chung, Sheng-ying; Liu, Chu-feng; Sun, Cheuk-kwan; Chang, Hsueh-wen; Zhen, Yen-yi; Lee, Fan-yen; Yip, Hon-kan

    2016-01-01

    Aim: Antioxidant peptide SS-31 is a class of cell-permeable small peptides, which selectively resides on the inner mitochondrial membrane and possesses intrinsic mitochondrial protective capacities. In this study we investigated the therapeutic effects of antioxidant peptide SS-31 on transverse aortic constriction (TAC)-induced pulmonary arterial hypertension (PAH) in a murine model. Methods: Adult male mice were divided into 3 groups: sham-operated mice, TAC mice, and TAC+SS-31 mice that underwent TAC surgery and received SS-31 (2 mg/d, ip) for 60 d. The right ventricular systolic blood pressure (RVSBP) was measured on d 60 prior to sacrificing the mice; then their right heart and lung tissues were collected for histological and biochemical examinations. Lung injury scores were defined by the increased crowded area and decreased number of alveolar sacs. Results: TAC mice showed significantly higher RVSBP compared with sham-operated mice, the elevation was substantially suppressed in TAC+SS-31 mice. The same pattern of changes was found in pulmonary levels of oxidative stress proteins (NOX-1/NOX-2/oxidized proteins), cytosolic cytochrome c, biomarkers related to inflammation (MMP-9/TNF-α/iNOS), calcium overload index (TRPC1, 2, 4, 6), apoptosis (mitochondrial BAX, cleaved caspase 3/PARP), fibrosis (Smad3/TGF-β), hypoxic (HIF-1α), DNA damage (γ-H2AX) and endothelial function (eNOS/ET-1R), as well as in lung injury score, number of muscularized vessels in lungs, number of TRPC1+ and HIF-1α+ cells in pulmonary artery, and number of γ-H2AX+ and Ki-67+ cells in lung parenchyma. An opposite pattern of changes was observed in pulmonary anti-fibrotic markers (Smad1/5, BMP-2), number of small vessels, and number of alveolar sacs. In contrast, the levels of antioxidant proteins (HO-1/NQO-1/GR/GPx) in lung parenchyma were progressively and significantly increased from sham-operated mice, TAC mice to TAC+SS-31 mice. Conclusion: Antioxidant peptide SS-31 administration

  18. Glucocorticoid receptor haploinsufficiency causes hypertension and attenuates hypothalamic-pituitary-adrenal axis and blood pressure adaptions to high-fat diet.

    PubMed

    Michailidou, Z; Carter, R N; Marshall, E; Sutherland, H G; Brownstein, D G; Owen, E; Cockett, K; Kelly, V; Ramage, L; Al-Dujaili, E A S; Ross, M; Maraki, I; Newton, K; Holmes, M C; Seckl, J R; Morton, N M; Kenyon, C J; Chapman, K E

    2008-11-01

    Glucocorticoid hormones are critical to respond and adapt to stress. Genetic variations in the glucocorticoid receptor (GR) gene alter hypothalamic-pituitary-adrenal (HPA) axis activity and associate with hypertension and susceptibility to metabolic disease. Here we test the hypothesis that reduced GR density alters blood pressure and glucose and lipid homeostasis and limits adaption to obesogenic diet. Heterozygous GR(betageo/+) mice were generated from embryonic stem (ES) cells with a gene trap integration of a beta-galactosidase-neomycin phosphotransferase (betageo) cassette into the GR gene creating a transcriptionally inactive GR fusion protein. Although GR(betageo/+) mice have 50% less functional GR, they have normal lipid and glucose homeostasis due to compensatory HPA axis activation but are hypertensive due to activation of the renin-angiotensin-aldosterone system (RAAS). When challenged with a high-fat diet, weight gain, adiposity, and glucose intolerance were similarly increased in control and GR(betageo/+) mice, suggesting preserved control of intermediary metabolism and energy balance. However, whereas a high-fat diet caused HPA activation and increased blood pressure in control mice, these adaptions were attenuated or abolished in GR(betageo/+) mice. Thus, reduced GR density balanced by HPA activation leaves glucocorticoid functions unaffected but mineralocorticoid functions increased, causing hypertension. Importantly, reduced GR limits HPA and blood pressure adaptions to obesogenic diet. PMID:18697839

  19. The Role of the Kallikrein-Kinin System Genes in the Salt Sensitivity of Blood Pressure

    PubMed Central

    Gu, Dongfeng; Zhao, Qi; Kelly, Tanika N.; Hixson, James E.; Rao, Dabeeru C.; Cao, Jie; Chen, Jing; Li, Jianxin; Chen, Jichun; Ji, Xu; Hu, Dongsheng; Wang, Xushan; Liu, De-Pei; He, Jiang

    2012-01-01

    The current study comprehensively examined the association between common genetic variants of the kallikrein-kinin system (KKS) and blood pressure salt sensitivity. A 7-day low-sodium followed by a 7-day high-sodium dietary intervention was conducted among 1,906 Han Chinese participants recruited from 2003 to 2005. Blood pressure was measured by using a random-zero sphygmomanometer through the study. A total of 205 single nucleotide polymorphisms (SNPs) covering 11 genes of the KKS were selected for the analyses. Genetic variants of the bradykinin receptor B2 gene (BDKRB2) and the endothelin converting enzyme 1 gene (ECE1) showed significant associations with the salt-sensitivity phenotypes even after adjustment for multiple testing. Compared with the major G allele, the BDKRB2 rs11847625 minor C allele was significantly associated with increased systolic blood pressure responses to low-sodium intervention (P = 0.0001). Furthermore, a haplotype containing allele C was associated with an increased systolic blood pressure response to high-sodium intervention (P = 0.0009). Seven highly correlated ECE1 SNPs were shown to increase the diastolic blood pressure response to low-sodium intervention (P values ranged from 0.0003 to 0.002), with 2 haplotypes containing these 7 SNPs also associated with this same phenotype (P values ranged from 0.0004 to 0.002). In summary, genetic variants of the genes involved in the regulation of KKS may contribute to the salt sensitivity of blood pressure. PMID:23035147

  20. High Salt Intake Promotes Urinary Loss of Vitamin D Metabolites by Dahl Salt-Sensitive Rats in a Space Flight Model

    NASA Technical Reports Server (NTRS)

    Thierry-Palmer, M.; Cephas, S.; Sayavongsa, P.; Clark, T.; Arnaud, S. B.

    2004-01-01

    Vitamin D metabolism in the Dahl salt-sensitive (S) rat, a model of salt-induced hypertension, differs from that in the Dahl salt-resistant (R) rat. We have demonstrated that female S rats are more vulnerable than female R rats to decreases in plasma 25-hydroxyvitamin D (25-OHD) and 1,25-dihydroxyvitamin D (1,25-(OH)2D) concentrations during hind limb unloading (a space flight model). We report here on the response of the vitamin D endocrine system of S and R rats to hind limb unloading during high salt intake. Dahl female rats (9.7-week-old) were tail-suspended (hind limb unloaded) for 28 days, while fed a diet containing twice the salt in standard rat chow (2 % sodium chloride). Control rats were fed the same diet, but were not hind limb unloaded. Vitamin D metabolites were analyzed by HPLC and radioimmunoassay kits from Diasorin.

  1. Over-expression of copper/zinc superoxide dismutase in the median preoptic nucleus attenuates chronic angiotensin II-induced hypertension in the rat.

    PubMed

    Collister, John P; Bellrichard, Mitch; Drebes, Donna; Nahey, David; Tian, Jun; Zimmerman, Matthew C

    2014-01-01

    The brain senses circulating levels of angiotensin II (AngII) via circumventricular organs, such as the subfornical organ (SFO), and is thought to adjust sympathetic nervous system output accordingly via this neuro-hormonal communication. However, the cellular signaling mechanisms involved in these communications remain to be fully understood. Previous lesion studies of either the SFO, or the downstream median preoptic nucleus (MnPO) have shown a diminution of the hypertensive effects of chronic AngII, without providing a clear explanation as to the intracellular signaling pathway(s) involved. Additional studies have reported that over-expressing copper/zinc superoxide dismutase (CuZnSOD), an intracellular superoxide (O2·-) scavenging enzyme, in the SFO attenuates chronic AngII-induced hypertension. Herein, we tested the hypothesis that overproduction of O2·- in the MnPO is an underlying mechanism in the long-term hypertensive effects of chronic AngII. Adenoviral vectors encoding human CuZnSOD (AdCuZnSOD) or control vector (AdEmpty) were injected directly into the MnPO of rats implanted with aortic telemetric transmitters for recording of arterial pressure. After a 3 day control period of saline infusion, rats were intravenously infused with AngII (10 ng/kg/min) for ten days. Rats over-expressing CuZnSOD (n = 7) in the MnPO had a blood pressure increase of only 6 ± 2 mmHg after ten days of AngII infusion while blood pressure increased 21 ± 4 mmHg in AdEmpty-infected rats (n = 9). These results support the hypothesis that production of O2·- in the MnPO contributes to the development of chronic AngII-dependent hypertension. PMID:25474089

  2. Angiotensin II-Induced Hypertension Is Attenuated by Reduction of Sympathetic Output in NO-Sensitive Guanylyl Cyclase 1 Knockout Mice.

    PubMed

    Broekmans, Kathrin; Stegbauer, Johannes; Potthoff, Sebastian A; Russwurm, Michael; Koesling, Doris; Mergia, Evanthia

    2016-01-01

    In the regulation of vascular tone, the dilatory nitric oxide (NO)/cGMP pathway balances vasoconstriction induced by the renin-angiotensin and sympathetic nervous systems. NO-induced cGMP formation is catalyzed by two guanylyl cyclases (GC), NO-sensitive guanylyl cyclase 1 (NO-GC1) and NO-GC2, with indistinguishable enzymatic properties. In vascular smooth muscle cells, NO-GC1 is the major isoform and is responsible for more than 90% of cGMP formation. Despite reduced vasorelaxation, NO-GC1-deficient mice are not hypertensive. Here, the role of NO-GC1 in hypertension provoked by contractile agonists angiotensin II (Ang II) and norepinephrine (NE) was evaluated in NO-GC1-deficient mice. Hypertension induced by chronic Ang II treatment did not differ between wild-type (WT) and NO-GC1 knockout mice (KO). Also, attenuation of NO-dependent aortic relaxation induced by the Ang II treatment was similar in both genotypes and was most probably attributable to an increase of phosphodiesterase 1 expression. Analysis of plasma NE content-known to be influenced by Ang II-revealed lower NE in the NO-GC1 KO under Ang II-treated- and nontreated conditions. The finding indicates reduced sympathetic output and is underlined by the lower heart rate in the NO-GC1 KO. To find out whether the lack of higher blood pressure in the NO-GC1 KO is a result of reduced sympathetic activity counterbalancing the reduced vascular relaxation, mice were challenged with chronic NE application. As the resulting blood pressure was higher in the NO-GC1 KO than in WT, we conclude that the reduced sympathetic activity in the NO-GC1 KO prevents hypertension and postulate a possible sympatho-excitatory action of NO-GC1 counteracting NO-GC1's dilatory effect in the vasculature. PMID:26559126

  3. Comparing Clonidine and Lidocaine on Attenuation of Hemodynamic Responses to Laryngoscopy and Tracheal Intubation in Controlled Hypertensive Patients: A Randomized, Double-Blinded Clinical Trial

    PubMed Central

    Soltani Mohammadi, Sussan; Maziar, Alireza; Saliminia, Alireza

    2016-01-01

    Background: Hemodynamic fluctuations in response to laryngoscopy and tracheal intubation and their potential hazards have been well-recognized, especially in hypertensive patients. Many drugs in various combinations have been used to attenuate these adverse responses. Objectives: We conducted a study to compare lidocaine with clonidine on the attenuation of hemodynamic responses to laryngoscopy and tracheal intubation, in controlled hypertensive patients undergoing general anesthesia. Patients and Methods: Eighty-six patients of American society of anesthesiologists (ASA) class II, who were aged 18 to 65-years-old and were scheduled for elective surgeries under general anesthesia, were included. The patients were randomly divided into two equal groups. The clonidine group received 0.2 mg oral clonidine 90 minutes before surgery and the lidocaine group received a placebo tablet at the same time. All patients in both groups were anesthetized with the same technique, including: intravenous fentanyl 3 mcg/kg, sodium thiopental 5 mg/kg, and atracurium 0.5 mg/kg. The lidocaine group received 1.5 mg/kg lidocaine but the clonidine group received the same volume of saline ninety seconds before intubation. Hemodynamic parameters were recorded before intubation and 1, 3, 5, and 10 minutes after endotracheal intubation. Results: There were no significant differences between the two groups’ hemodynamic parameters, including heart rate and systolic, diastolic, and mean arterial blood pressures at the measured points. There were also no significant differences within each group in hemodynamic responses at the measured points (P > 0.05). Twenty patients in the clonidine and three patients in the lidocaine group complained of mouth dryness (P = 0.001). Fourteen patients in the clonidine and four patients in the lidocaine group had bradycardia (P = 0.008). Nineteen patients in the clonidine and six patients in the lidocaine group had orthostatic hypotension (P = 0

  4. Hemodynamics and Salt-and-Water Balance Link Sodium Storage and Vascular Dysfunction in Salt-Sensitive Subjects.

    PubMed

    Laffer, Cheryl L; Scott, Robert C; Titze, Jens M; Luft, Friedrich C; Elijovich, Fernando

    2016-07-01

    We investigated 24-hour hemodynamic changes produced by salt loading and depletion in 8 salt-sensitive (SS) and 13 salt-resistant (SR) normotensive volunteers. After salt loading, mean arterial pressure was higher in SS (96.5±2.8) than in SR (84.2±2.7 mm Hg), P<0.01, owing to higher total peripheral resistance in SS (1791±148) than in SR (1549±66 dyn*cm(-5)*s), P=0.05, whereas cardiac output was not different between groups (SS 4.5±0.3 versus SR 4.4±0.2 L/min, not significant). Following salt depletion, cardiac output was equally reduced in both groups. Total peripheral resistance increased 24±6% (P<0.001) in SR, whose mean arterial pressure remained unchanged. In contrast, total peripheral resistance did not change in SS (1±6%, not significant). Thus, their mean arterial pressure was reduced, abolishing the mean arterial pressure difference between groups. SS had higher E/e' ratios than SR in both phases of the protocol. In these 21 subjects and in 32 hypertensive patients, Na(+) balance was similar in SR and SS during salt loading or depletion. However, SR did not gain weight during salt retention (-158±250 g), whereas SS did (819±204), commensurate to iso-osmolar water retention. During salt depletion, SR lost the expected amount of weight for iso-osmolar Na(+) excretion, whereas SS lost a greater amount that failed to fully correct the fluid retention from the previous day. We conclude that SS are unable to modulate total peripheral resistance in response to salt depletion, mirroring their inability to vasodilate in response to salt loading. We suggest that differences in water balance between SS and SR indicate differences in salt-and-water storage in the interstitial compartment that may relate to vascular dysfunction in SS. PMID:27160204

  5. Genetic influence on brain catecholamines: high brain norepinephrine in salt-sensitive rats

    SciTech Connect

    Iwai, J; Friedman, R; Tassinari, L

    1980-01-01

    Rats genetically sensitive to salt-induced hypertension evinced higher levels of plasma norepinephrine and epinephrine than rats genetically resistant to hypertension. The hypertension-sensitive rats showed higher hypothalamic norepinephrine and lower epinephrine than resistant rats. In response to a high salt diet, brain stem norepinephrine increased in sensitive rats while resistant rats exhibited a decrease on the same diet.

  6. Immunization with an ApoB-100 Related Peptide Vaccine Attenuates Angiotensin-II Induced Hypertension and Renal Fibrosis in Mice

    PubMed Central

    Honjo, Tomoyuki; Chyu, Kuang-Yuh; Dimayuga, Paul C.; Lio, Wai Man; Yano, Juliana; Trinidad, Portia; Zhao, Xiaoning; Zhou, Jianchang; Cercek, Bojan; Shah, Prediman K.

    2015-01-01

    Recent studies suggest the potential involvement of CD8+ T cells in the pathogenesis of murine hypertension. We recently reported that immunization with apoB-100 related peptide, p210, modified CD8+ T cell function in angiotensin II (AngII)-infused apoE (-/-) mice. In this study, we hypothesized that p210 vaccine modulates blood pressure in AngII-infused apoE (-/-) mice. Male apoE (-/-) mice were immunized with p210 vaccine and compared to unimmunized controls. At 10 weeks of age, mice were subcutaneously implanted with an osmotic pump which released AngII for 4 weeks. At 13 weeks of age, p210 immunized mice showed significantly lower blood pressure response to AngII compared to controls. CD8+ T cells from p210 immunized mice displayed a different phenotype compared to CD8+ T cells from unimmunized controls. Serum creatinine and urine albumin to creatinine ratio were significantly decreased in p210 immunized mice suggesting that p210 vaccine had renal protective effect. At euthanasia, inflammatory genes IL-6, TNF-α, and MCP-1 in renal tissue were down-regulated by p210 vaccine. Renal fibrosis and pro-fibrotic gene expression were also significantly reduced in p210 immunized mice. To assess the role of CD8+ T cells in these beneficial effects of p210 vaccine, CD8+ T cells were depleted by CD8 depleting antibody in p210 immunized mice. p210 immunized mice with CD8+ T cell depletion developed higher blood pressure compared to mice receiving isotype control. Depletion of CD8+ T cells also increased renal fibrotic gene expression compared to controls. We conclude that immunization with p210 vaccine attenuated AngII-induced hypertension and renal fibrosis. CD8+ T cells modulated by p210 vaccine could play an important role in the anti-hypertensive, anti-fibrotic and renal-protective effect of p210 vaccine. PMID:26121471

  7. Long-Term Treatment with Losartan Attenuates Seizure Activity and Neuronal Damage Without Affecting Behavioral Changes in a Model of Co-morbid Hypertension and Epilepsy.

    PubMed

    Tchekalarova, Jana D; Ivanova, Natasha; Atanasova, Dimitrina; Pechlivanova, Daniela M; Lazarov, Nikolai; Kortenska, Lidia; Mitreva, Rumiana; Lozanov, Valentin; Stoynev, Alexander

    2016-08-01

    Over the last 10 years, accumulated experimental and clinical evidence has supported the idea that AT1 receptor subtype is involved in epilepsy. Recently, we have shown that the selective AT1 receptor antagonist losartan attenuates epileptogenesis and exerts neuroprotection in the CA1 area of the hippocampus in epileptic Wistar rats. This study aimed to verify the efficacy of long-term treatment with losartan (10 mg/kg) after kainate-induced status epilepticus (SE) on seizure activity, behavioral and biochemical changes, and neuronal damage in a model of co-morbid hypertension and epilepsy. Spontaneous seizures were video- and EEG-monitored in spontaneously hypertensive rats (SHRs) for a 16-week period after SE. The behavior was analyzed by open field, elevated plus maze, sugar preference test, and forced swim test. The levels of serotonin in the hippocampus and neuronal loss were estimated by HPLC and hematoxylin and eosin staining, respectively. The AT1 receptor antagonism delayed the onset of seizures and alleviated their frequency and duration during and after discontinuation of treatment. Losartan showed neuroprotection mostly in the CA3 area of the hippocampus and the septo-temporal hilus of the dentate gyrus in SHRs. However, the AT1 receptor antagonist did not exert a substantial influence on concomitant with epilepsy behavioral changes and decreased 5-HT levels in the hippocampus. Our results suggest that the antihypertensive therapy with an AT1 receptor blocker might be effective against seizure activity and neuronal damage in a co-morbid hypertension and epilepsy. PMID:26464042

  8. Chronic in vivo or acute in vitro resveratrol attenuates endothelium-dependent cyclooxygenase-mediated contractile signaling in hypertensive rat carotid artery.

    PubMed

    Denniss, Steven G; Ford, Rebecca J; Smith, Christopher S; Jeffery, Andrew J; Rush, James W E

    2016-05-15

    Exaggerated cyclooxygenase (COX) and thromboxane-prostanoid (TP) receptor-mediated endothelium-dependent contraction can contribute to endothelial dysfunction. This study examined the effect of resveratrol (RSV) on endothelium-dependent contraction and cell signaling in the common carotid artery (CCA) from spontaneously hypertensive rats (SHR) and Wistar Kyoto rats (WKY). Acetylcholine (Ach)-stimulated endothelium-dependent nitric oxide synthase (NOS)-mediated relaxation in precontracted SHR CCA was impaired (maximum 73 ± 6% vs. 87 ± 5% in WKY) (P < 0.05) by competitive COX-mediated contraction. Chronic (28-day) treatment in vivo (drinking water) with a ∼0.075 mg·kg(-1)·day(-1) RSV dose affected neither endothelium-dependent relaxation nor endothelium-dependent contraction and associated prostaglandin (PG) production evaluated in non-precontracted NOS-blocked CCA. In contrast, a chronic ∼7.5 mg·kg(-1)·day(-1) RSV dose improved endothelium-dependent relaxation (94 ± 6%) and attenuated endothelium-dependent contraction (58 ± 4% vs. 73 ± 5% in No-RSV) and PG production (183 ± 43 vs. 519 ± 93 pg/ml) in SHR CCA, while U46619-stimulated TP receptor-mediated contraction was unaffected. In separate acute in vitro experiments, 20-μM RSV preincubation attenuated endothelium-dependent contraction (6 ± 4% vs. 62 ± 2% in No Drug) and PG production (121 ± 15 vs. 491 ± 93 pg/ml) and attenuated U46619-stimulated contraction (134 ± 5% vs. 171 ± 4%) in non-precontracted NOS-blocked SHR CCA. Compound C, a known AMP-activated protein kinase (AMPK) inhibitor, did not prevent the RSV attenuating effect on Ach- and U46619-stimulated contraction but did prevent the RSV attenuating effect on PG production (414 ± 58 pg/ml). These data demonstrate that RSV can attenuate endothelium-dependent contraction both by suppressing arterial wall PG production, which may be partially mediated by AMPK, and by TP receptor hyporesponsiveness, which does not appear to be mediated by

  9. Salt-Sensitive Mutants of Chlamydomonas reinhardtii Isolated after Insertional Tagging.

    PubMed Central

    Prieto, R.; Pardo, J. M.; Niu, X.; Bressan, R. A.; Hasegawa, P. M.

    1996-01-01

    We describe the isolation of salt-sensitive Chlamydomonas reinhardtii mutants by insertional mutagenesis using the nitrate reductase (Nit1) gene. The plasmid pMN24, containing Nit1, was used for transformation of 305CW15 (nit1 cw15 mt+), and transformants were selected for complementation of the nit- phenotype. From 6875 nit+ colonies, four transformants (S4, S18, S46, and S66) were isolated that exhibited both Na+ and Li+ sensitivity (sod-), and another transformant (S33) was selected that exhibited sensitivity to Li+ but not Na+ (lit-) based on relative growth comparisons with the wild-type strain. S33, S46, and S66 were no more growth inhibited by sorbitol than was 305CW15. In comparison, S4 and S18 exhibited substantial growth inhibition in medium supplemented with sorbitol. Genetic analyses indicated that the salt-sensitive mutants were each defective in a single recessive gene. The mutant genes in S4 (sod1), S33 (lit1), and S66 (sod3) are linked to a functional copy of Nit1 and are presumably tagged with a pMN24 insertion. PMID:12226377

  10. Pulmonary hypertension

    MedlinePlus

    Pulmonary arterial hypertension; Sporadic primary pulmonary hypertension; Familial primary pulmonary hypertension; Idiopathic pulmonary arterial hypertension; Primary pulmonary hypertension; PPH; Secondary pulmonary ...

  11. Moderate postnatal hyperoxia accelerates lung growth and attenuates pulmonary hypertension in infant rats after exposure to intra-amniotic endotoxin.

    PubMed

    Tang, Jen-Ruey; Seedorf, Gregory J; Muehlethaler, Vincent; Walker, Deandra L; Markham, Neil E; Balasubramaniam, Vivek; Abman, Steven H

    2010-12-01

    To determine the separate and interactive effects of fetal inflammation and neonatal hyperoxia on the developing lung, we hypothesized that: 1) antenatal endotoxin (ETX) causes sustained abnormalities of infant lung structure; and 2) postnatal hyperoxia augments the adverse effects of antenatal ETX on infant lung growth. Escherichia coli ETX or saline (SA) was injected into amniotic sacs in pregnant Sprague-Dawley rats at 20 days of gestation. Pups were delivered 2 days later and raised in room air (RA) or moderate hyperoxia (O₂, 80% O₂ at Denver's altitude, ∼65% O₂ at sea level) from birth through 14 days of age. Heart and lung tissues were harvested for measurements. Intra-amniotic ETX caused right ventricular hypertrophy (RVH) and decreased lung vascular endothelial growth factor (VEGF) and VEGF receptor-2 (VEGFR-2) protein contents at birth. In ETX-exposed rats (ETX-RA), alveolarization and vessel density were decreased, pulmonary vascular wall thickness percentage was increased, and RVH was persistent throughout the study period compared with controls (SA-RA). After antenatal ETX, moderate hyperoxia increased lung VEGF and VEGFR-2 protein contents in ETX-O₂ rats and improved their alveolar and vascular structure and RVH compared with ETX-RA rats. In contrast, severe hyperoxia (≥95% O₂ at Denver's altitude) further reduced lung vessel density after intra-amniotic ETX exposure. We conclude that intra-amniotic ETX induces fetal pulmonary hypertension and causes persistent abnormalities of lung structure with sustained pulmonary hypertension in infant rats. Moreover, moderate postnatal hyperoxia after antenatal ETX restores lung growth and prevents pulmonary hypertension during infancy. PMID:20709730

  12. Azilsartan Improves Salt Sensitivity by Modulating the Proximal Tubular Na+-H+ Exchanger-3 in Mice

    PubMed Central

    Hatanaka, Masaki; Kaimori, Jun-Ya; Yamamoto, Satoko; Matsui, Isao; Hamano, Takayuki; Takabatake, Yoshitsugu; Ecelbarger, Carolyn M.; Takahara, Shiro; Isaka, Yoshitaka; Rakugi, Hiromi

    2016-01-01

    A potent angiotensin II type-1 receptor blocker, azilsartan, has been reported to reduce blood pressure more effectively than candesartan. Interestingly, azilsartan can also restore the circadian rhythm of blood pressure. We hypothesized that azilsartan could also improve salt sensitivity; thus, we examined the effect of azilsartan on sodium handling in renal tubules. Subtotal nephrectomized C57BL/6 mice received azilsartan (1.0 mg/kg/day), candesartan (0.3 mg/kg/day), or vehicle via the oral route in conjunction with a normal- (0.3%) or high-salt (8.0%) diet. Two weeks later, the azilsartan group showed significantly lower blood pressure during the light period than the candesartan and vehicle groups (azilsartan: 103.1 ± 1.0; candesartan: 111.7 ± 2.7; vehicle: 125.5 ± 2.5 mmHg; P < 0.05; azilsartan or candesartan vs. vehicle). The azilsartan group also showed higher urinary fractional excretion of sodium during the dark period than the candesartan and vehicle groups (azilsartan: 21.37 ± 3.69%; candesartan: 14.17 ± 1.42%; vehicle: 13.85 ± 5.30%; P < 0.05 azilsartan vs. candesartan or vehicle). A pressure—natriuresis curve demonstrated that azilsartan treatment restored salt sensitivity. Immunofluorescence and western blotting showed lower levels of Na+-H+ exchanger-3 (NHE3) protein (the major sodium transporter in renal proximal tubules) in the azilsartan group, but not in the candesartan or vehicle groups. However, azilsartan did not affect NHE3 transcription levels. Interestingly, we did not observe increased expression of downstream sodium transporters, which would have compensated for the increased flow of sodium and water due to non-absorption by NHE3. We also confirmed the mechanism stated above using cultured opossum kidney proximal tubular cells. Results revealed that a proteasomal inhibitor (but not a lysosomal inhibitor) blocked the azilsartan-induced decrease in NHE3 protein expression, suggesting that azilsartan increases NHE3 ubiquitination. In

  13. Azilsartan Improves Salt Sensitivity by Modulating the Proximal Tubular Na+-H+ Exchanger-3 in Mice.

    PubMed

    Hatanaka, Masaki; Kaimori, Jun-Ya; Yamamoto, Satoko; Matsui, Isao; Hamano, Takayuki; Takabatake, Yoshitsugu; Ecelbarger, Carolyn M; Takahara, Shiro; Isaka, Yoshitaka; Rakugi, Hiromi

    2016-01-01

    A potent angiotensin II type-1 receptor blocker, azilsartan, has been reported to reduce blood pressure more effectively than candesartan. Interestingly, azilsartan can also restore the circadian rhythm of blood pressure. We hypothesized that azilsartan could also improve salt sensitivity; thus, we examined the effect of azilsartan on sodium handling in renal tubules. Subtotal nephrectomized C57BL/6 mice received azilsartan (1.0 mg/kg/day), candesartan (0.3 mg/kg/day), or vehicle via the oral route in conjunction with a normal- (0.3%) or high-salt (8.0%) diet. Two weeks later, the azilsartan group showed significantly lower blood pressure during the light period than the candesartan and vehicle groups (azilsartan: 103.1 ± 1.0; candesartan: 111.7 ± 2.7; vehicle: 125.5 ± 2.5 mmHg; P < 0.05; azilsartan or candesartan vs. vehicle). The azilsartan group also showed higher urinary fractional excretion of sodium during the dark period than the candesartan and vehicle groups (azilsartan: 21.37 ± 3.69%; candesartan: 14.17 ± 1.42%; vehicle: 13.85 ± 5.30%; P < 0.05 azilsartan vs. candesartan or vehicle). A pressure-natriuresis curve demonstrated that azilsartan treatment restored salt sensitivity. Immunofluorescence and western blotting showed lower levels of Na+-H+ exchanger-3 (NHE3) protein (the major sodium transporter in renal proximal tubules) in the azilsartan group, but not in the candesartan or vehicle groups. However, azilsartan did not affect NHE3 transcription levels. Interestingly, we did not observe increased expression of downstream sodium transporters, which would have compensated for the increased flow of sodium and water due to non-absorption by NHE3. We also confirmed the mechanism stated above using cultured opossum kidney proximal tubular cells. Results revealed that a proteasomal inhibitor (but not a lysosomal inhibitor) blocked the azilsartan-induced decrease in NHE3 protein expression, suggesting that azilsartan increases NHE3 ubiquitination. In

  14. Limiting collagen turnover via collagenase-resistance attenuates right ventricular dysfunction and fibrosis in pulmonary arterial hypertension.

    PubMed

    Golob, Mark J; Wang, Zhijie; Prostrollo, Anthony J; Hacker, Timothy A; Chesler, Naomi C

    2016-06-01

    Pulmonary arterial hypertension (PAH) is a severe form of pulmonary hypertension in which right ventricular (RV) afterload is increased and death typically occurs due to decompensated RV hypertrophy and failure. Collagen accumulation has been implicated in pulmonary artery remodeling, but how it affects RV performance remains unclear. Here, we sought to identify the role of collagen turnover, defined as the balance between collagen synthesis and degradation, in RV structure and function in PAH To do so, we exposed mutant (Col1a1(R/R)) mice, in which collagen type I degradation is impaired such that collagen turnover is reduced, and wild-type (Col1a1(+/+)) littermates to 14 days of chronic hypoxia combined with SUGEN treatment (HySu) to recapitulate characteristics of clinical PAH RV structure and function were measured by echocardiography, RV catheterization, and histology. Despite comparable increases in RV systolic pressure (Col1a1(+/+): 46 ± 2 mmHg; Col1a1(R/R): 47 ± 3 mmHg), the impaired collagen degradation in Col1a1(R/R) mice resulted in no RV collagen accumulation, limited RV hypertrophy, and maintained right ventricular-pulmonary vascular coupling with HySu exposure. The preservation of cardiac function in the mutant mice indicates a beneficial role of limited collagen turnover via impaired degradation in RV remodeling in response to chronic pressure overload. Our results suggest novel treatments that reduce collagen turnover may offer a new therapeutic strategy for PAH patients. PMID:27252252

  15. Losartan Attenuates Myocardial Endothelial-To-Mesenchymal Transition in Spontaneous Hypertensive Rats via Inhibiting TGF-β/Smad Signaling

    PubMed Central

    Wu, Miao; Peng, Zhenyu; Zu, Changhao; Ma, Jing; Lu, Shijuan; Zhong, Jianghua; Zhang, Saidan

    2016-01-01

    Background Losartan plays an important role in the inhibition of myocardial fibrosis. But the underlying mechanism is not entirely clear. Emerging evidences have indicated that endothelial-to-mesenchymal transition (EndMT) plays a crucial role in cardiac fibrosis. Here the present study aims to first investigated the effect of Losartan on EndMT in cardiac fibrosis of spontaneous hypertensive rats (SHRs). Methods Male SHRs were randomly divided into three groups and fed for 12 weeks, namely the SHR group (Group S), the Losartan-treated group (Group L) and the Prazosin-treated group (Group P). Wistar-Kyoto rats served as controls (Group W). The histological changes were evaluated by Masson’s trichrome. Co-expression of CD31 and fibroblast-specific protein 1 (FSP1) were used as the markers of EndMT through immunofluorescence. The expressions of FSP1, CD31, TGF-β, Smad were detected by Western blot analysis. Results It was identified that elevated blood pressure induced a significant increase in myocardial fibrosis and EndMT in SHRs, which was reversed by Losartan and Prazosin treatment. Furthermore, the activity of TGF-β/Smad signaling was detected in the four groups. TGF-β/Smad signaling was activated in SHRs and suppressed by Losartan or Prazosin treatment. Losartan exhibited more efficiently than Prazosin in inhibiting TGF-β/Smad signaling activation, EndMT and myocardial fibrosis. Conclusion These results showed that EndMT played an important role in promoting hypertensive cardiac fibrosis, and that losartan could suppress cardiac fibrosis through the inhibition of EndMT via classical TGF-β/Smad pathway. PMID:27176484

  16. p66Shc regulates renal vascular tone in hypertension-induced nephropathy.

    PubMed

    Miller, Bradley; Palygin, Oleg; Rufanova, Victoriya A; Chong, Andrew; Lazar, Jozef; Jacob, Howard J; Mattson, David; Roman, Richard J; Williams, Jan M; Cowley, Allen W; Geurts, Aron M; Staruschenko, Alexander; Imig, John D; Sorokin, Andrey

    2016-07-01

    Renal preglomerular arterioles regulate vascular tone to ensure a large pressure gradient over short distances, a function that is extremely important for maintaining renal microcirculation. Regulation of renal microvascular tone is impaired in salt-sensitive (SS) hypertension-induced nephropathy, but the molecular mechanisms contributing to this impairment remain elusive. Here, we assessed the contribution of the SH2 adaptor protein p66Shc (encoded by Shc1) in regulating renal vascular tone and the development of renal vascular dysfunction associated with hypertension-induced nephropathy. We generated a panel of mutant rat strains in which specific modifications of Shc1 were introduced into the Dahl SS rats. In SS rats, overexpression of p66Shc was linked to increased renal damage. Conversely, deletion of p66Shc from these rats restored the myogenic responsiveness of renal preglomerular arterioles ex vivo and promoted cellular contraction in primary vascular smooth muscle cells (SMCs) that were isolated from renal vessels. In primary SMCs, p66Shc restricted the activation of transient receptor potential cation channels to attenuate cytosolic Ca2+ influx, implicating a mechanism by which overexpression of p66Shc impairs renal vascular reactivity. These results establish the adaptor protein p66Shc as a regulator of renal vascular tone and a driver of impaired renal vascular function in hypertension-induced nephropathy. PMID:27270176

  17. Distance dependence and salt sensitivity of pairwise, coulombic interactions in a protein

    PubMed Central

    Lee, Kelly K.; Fitch, Carolyn A.; García-Moreno E., Bertrand

    2002-01-01

    Histidine pKa values were measured in charge-reversal (K78E, K97E, K127E, and K97E/K127E) and charge-neutralization (E10A, E101A, and R35A) mutants of staphylococcal nuclease (SNase) by 1H-NMR spectroscopy. Energies of interaction between pairs of charges (ΔGij) were obtained from the shifts in pKa values relative to wild-type values. The data describe the distance dependence and salt sensitivity of pairwise coulombic interactions. Calculations with a continuum electrostatics method captured the experimental ΔGij when static structures were used and when the protein interior was treated empirically with a dielectric constant of 20. The ΔGij when rij ≤ 10 Å were exaggerated slightly in the calculations. Coulomb's law with a dielectric constant near 80 and a Debye-Hückel term to account for screening by the ionic strength reproduced the salt sensitivity and distance dependence of ΔGij as well as the structure-based method. In their interactions with each other, surface charges behave as if immersed in water; the Debye length describes realistically the distance where interactions become negligible at a given ionic strength. On average, charges separated by distances (rij) ≈5 Å interacted with ΔGij ≈ 0.6 kcal/mole in 0.01 M KCl, but ΔGij decayed to ≤0.10 kcal/mole when rij = 20 Å. In 0.10 M KCl, ΔGij ≈ 0.10 kcal/mole when rij = 10 Å. In 1.5 M KCl, only short-range interactions with rij ≤ 5 Å persisted. Although at physiological ionic strengths the interactions between charges separated by more than 10 Å are extremely weak, in situations where charge imbalance exists many weak interactions can cumulatively produce substantial effects. PMID:11967358

  18. Trans-ethnic Fine Mapping Highlights Kidney-Function Genes Linked to Salt Sensitivity.

    PubMed

    Mahajan, Anubha; Rodan, Aylin R; Le, Thu H; Gaulton, Kyle J; Haessler, Jeffrey; Stilp, Adrienne M; Kamatani, Yoichiro; Zhu, Gu; Sofer, Tamar; Puri, Sanjana; Schellinger, Jeffrey N; Chu, Pei-Lun; Cechova, Sylvia; van Zuydam, Natalie; Arnlov, Johan; Flessner, Michael F; Giedraitis, Vilmantas; Heath, Andrew C; Kubo, Michiaki; Larsson, Anders; Lindgren, Cecilia M; Madden, Pamela A F; Montgomery, Grant W; Papanicolaou, George J; Reiner, Alex P; Sundström, Johan; Thornton, Timothy A; Lind, Lars; Ingelsson, Erik; Cai, Jianwen; Martin, Nicholas G; Kooperberg, Charles; Matsuda, Koichi; Whitfield, John B; Okada, Yukinori; Laurie, Cathy C; Morris, Andrew P; Franceschini, Nora

    2016-09-01

    We analyzed genome-wide association studies (GWASs), including data from 71,638 individuals from four ancestries, for estimated glomerular filtration rate (eGFR), a measure of kidney function used to define chronic kidney disease (CKD). We identified 20 loci attaining genome-wide-significant evidence of association (p < 5 × 10(-8)) with kidney function and highlighted that allelic effects on eGFR at lead SNPs are homogeneous across ancestries. We leveraged differences in the pattern of linkage disequilibrium between diverse populations to fine-map the 20 loci through construction of "credible sets" of variants driving eGFR association signals. Credible variants at the 20 eGFR loci were enriched for DNase I hypersensitivity sites (DHSs) in human kidney cells. DHS credible variants were expression quantitative trait loci for NFATC1 and RGS14 (at the SLC34A1 locus) in multiple tissues. Loss-of-function mutations in ancestral orthologs of both genes in Drosophila melanogaster were associated with altered sensitivity to salt stress. Renal mRNA expression of Nfatc1 and Rgs14 in a salt-sensitive mouse model was also reduced after exposure to a high-salt diet or induced CKD. Our study (1) demonstrates the utility of trans-ethnic fine mapping through integration of GWASs involving diverse populations with genomic annotation from relevant tissues to define molecular mechanisms by which association signals exert their effect and (2) suggests that salt sensitivity might be an important marker for biological processes that affect kidney function and CKD in humans. PMID:27588450

  19. Ocular Hypertension

    MedlinePlus

    ... Español Eye Health / Eye Health A-Z Ocular Hypertension Sections What Is Ocular Hypertension? Ocular Hypertension Causes ... Hypertension Diagnosis Ocular Hypertension Treatment What Is Ocular Hypertension? Written by: Kierstan Boyd Reviewed by: J Kevin ...

  20. Niflumic Acid Attenuated Pulmonary Artery Tone and Vascular Structural Remodeling of Pulmonary Arterial Hypertension Induced by High Pulmonary Blood Flow In Vivo.

    PubMed

    Wang, Kai; Ma, Jianfa; Pang, Yusheng; Lao, Jinquan; Pan, Xuanren; Tang, Qiaoyun; Zhang, Feng; Su, Danyan; Qin, Suyuan; Shrestha, Arnav Prasad

    2015-10-01

    Calcium-activated chloride channels (CaCCs) play a vital role in regulating pulmonary artery tone during pulmonary arterial hypertension (PAH) induced by high blood flow. The role of CaCCs inhibitor niflumic acid (NFA) in vivo during this process requires further investigation. We established the PAH model by abdominal shunt surgery and treated with NFA in vivo. Fifty rats were randomly divided into normal, sham, shunt, NFA group 1 (0.2 mg/kg), and NFA group 2 (0.4 mg/kg). Pathological changes, right ventricle hypertrophy index, arterial wall area/vessel area, and arterial wall thickness/vessel external diameter were analyzed. Then contraction reactions of pulmonary arteries were measured. Finally, the electrophysiological characteristics of pulmonary arterial smooth muscle cells were investigated using patch-clamp technology. After 11 weeks of shunting, PAH developed, accompanied with increased right ventricle hypertrophy index, arterial wall area/vessel area, and arterial wall thickness/vessel external diameter. In the NFA treatment groups, the pressure and pathological changes were alleviated. The pulmonary artery tone in the shunt group increased, whereas it decreased after NFA treatment. The current density of CaCC was higher in the shunt group, and it was decreased in the NFA treatment groups. In conclusion, NFA attenuated pulmonary artery tone and structural remodeling in PAH induced by high pulmonary blood flow in vivo. CaCCs were involved and the augmented current density was alleviated by NFA treatment. PMID:26132368

  1. Comparative assessment of ProSeal™ laryngeal mask airway intervention versus standard technique of endotracheal extubation for attenuation of pressor response in controlled hypertensive patients

    PubMed Central

    Singh, Raj Pal; Gulabani, Michell; Kaur, Mohandeep; Sood, Rajesh

    2016-01-01

    Background and Aims: Swapping of the endotracheal tube with laryngeal mask airway (LMA) before emergence from anaesthesia is one of the methods employed for attenuation of pressor response at extubation. We decided to compare the placement of ProSeal™ LMA (PLMA) before endotracheal extubation versus conventional endotracheal extubation in controlled hypertensive patients scheduled for elective surgeries under general anaesthesia. Methods: Sixty consenting adult patients were randomly allocated to two groups of thirty each; Group E in whom extubation was performed using standard technique and Group P in whom PLMA was inserted before endotracheal extubation (Bailey manoeuvre). The primary outcome parameter was heart rate (HR). The secondary outcomes were systolic, diastolic and mean blood pressure (MBP), electrocardiogram, oxygen saturation and end-tidal carbon dioxide. Two-tailed paired Student's t-test was used for comparison between the two study groups. The value of P < 0.05 was considered as statistically significant. Results: The patient characteristics, demographic data and surgical procedures were comparable in the two groups. A statistically significant decrease was observed in HR in Group P as compared to Group E. Secondary outcomes such as systolic, diastolic and MBP depicted a statistically insignificant difference. Conclusion: Bailey manoeuvre was not effective method to be completely relied upon during extubation when compared to standard extubation. PMID:27512160

  2. Electroacupuncture attenuates cervical spinal cord injury following cerebral ischemia/reperfusion in stroke-prone renovascular hypertensive rats

    PubMed Central

    TAN, FENG; CHEN, JIE; LIANG, YANGUI; GU, MINHUA; LI, YANPING; WANG, XUEWEN; MENG, DI

    2014-01-01

    Cerebral ischemia induces injury, not only in the ischemic core and surrounding penumbra tissues, but also in remote areas such as the cervical spinal cord. The aim of the present study was to determine the effects of electroacupuncture (EA) on cervical spinal cord injury following cerebral ischemia/reperfusion in stroke-prone renovascular hypertensive (RHRSP) rats. The results demonstrated that neuronal loss, which was assayed by Nissl staining in the cervical spinal cords of RHRSP rats subjected to transient middle cerebral artery occlusion (MCAO), was markedly decreased by EA stimulation at the GV20 (Baihui) and GV14 (Dazhui) acupoints compared with that in rats undergoing sham stimulation. Quantitative polymerase chain reaction and western blot analysis demonstrated that EA stimulation blocked the MCAO-induced elevated protein expression levels of glial fibrillary acidic protein and amyloid precursor protein in the cervical spinal cord at days 24 and 48. To further investigate the mechanism underlying the neuroprotective role of EA stimulation, the protein expression levels of Nogo-A and Nogo-66 receptor-1 (NgR1), two key regulatory molecules for neurite growth, were recorded in each group. The results revealed that EA stimulation reduced the MCAO-induced elevation of Nogo-A and NgR1 protein levels at day 14 and 28 in RHRSP rats. Therefore, the results demonstrated that EA reduced cervical spinal cord injury following cerebral ischemia in RHRSP rats, indicating that EA has the potential to be developed as a therapeutic treatment agent for cervical spinal cord injury following stroke. PMID:24926338

  3. The salt-sensitive structure and zinc inhibition of Borrelia burgdorferi protease BbHtrA.

    PubMed

    Russell, Theresa M; Tang, Xiaoling; Goldstein, Jason M; Bagarozzi, Dennis; Johnson, Barbara J B

    2016-02-01

    HtrA serine proteases are highly conserved and essential ATP-independent proteases with chaperone activity. Bacteria express a variable number of HtrA homologues that contribute to the virulence and pathogenicity of bacterial pathogens. Lyme disease spirochetes possess a single HtrA protease homologue, Borrelia burgdorferi HtrA (BbHtrA). Previous studies established that, like the human orthologue HtrA1, BbHtrA is proteolytically active against numerous extracellular proteins in vitro. In this study, we utilized size exclusion chromatography and blue native polyacrylamide gel electrophoresis (BN-PAGE) to demonstrate BbHtrA oligomeric structures that were substrate independent and salt sensitive. Examination of the influence of transition metals on the activity of BbHtrA revealed that this protease is inhibited by Zn(2+) > Cu(2+) > Mn(2+). Extending this analysis to two other HtrA proteases, E. coli DegP and HtrA1, revealed that all three HtrA proteases were reversibly inhibited by ZnCl2 at all micro molar concentrations examined. Commercial inhibitors for HtrA proteases are not available and physiologic HtrA inhibitors are unknown. Our observation of conserved zinc inhibition of HtrA proteases will facilitate structural and functional studies of additional members of this important class of proteases. PMID:26480895

  4. Drinking-induced bradyarrhythmias and cerebral injury in Dahl salt-sensitive rats with sinoaortic denervation.

    PubMed

    Abe, Chikara; Morita, Hironobu

    2013-11-01

    We have demonstrated that a drinking-induced pressor response was larger if the baroreflex did not operate, and the mean arterial pressure reached 163 mmHg in conscious rats with sinoaortic denervation (SAD). Thus we hypothesized that a drinking behavior became a cardiovascular risk factor if a basal arterial pressure was high. To clarify this, we analyzed the occurrence of arrhythmias and the accumulation of microglia in Dahl salt-sensitive rats (Dahl S) with SAD. We maintained Dahl S and Dahl salt-resistant rats (Dahl R) with a high-sodium diet for 5 weeks. After SAD surgery, we measured arterial pressure and electrocardiogram during water-drinking behavior in all rats. Furthermore, we measured tumor necrosis factor-α concentration in the cerebrospinal fluid (CSF) and microglial accumulations around the third and fourth ventricles in rats with programmed drinking at a rapid or slow rate for 7 days. Incidences of drinking-induced bradyarrhythmias and premature ventricular contractions (PVCs) were significantly larger in Dahl S than Dahl R rats. Both bradyarrhythmias and PVCs were completely abolished by atropine administration. Accumulations of microglia around the third ventricle and increases in TNF-α in the CSF were observed in rats that drank water at a rapid rate; these were not seen in rats that drank water slowly. In conclusion, both cardiovascular events and cerebral injury may be increased by drinking in Dahl S rats with SAD. These risks are reduced by modifying drinking behavior such as slowing the drinking rate. PMID:24072408

  5. Regulation of nitrogen metabolism in salt tolerant and salt sensitive Frankia strains.

    PubMed

    Srivastava, Amrita; Mishra, Arun Kumar

    2014-04-01

    Effect of salinity (0, 50, 100, 250, 500 and 750 mM NaCI) was observed on some important physiological parameters of nitrogen metabolism such as nitrate uptake, intracellular and extracellular ammonium status and activities of nitrogenase, nitrate reductase, nitrite reductase and glutamine synthetase among Frankia strains differing in their salt tolerance capacity. Nitrogenase activity closely followed the growth pattern with regular decline on NaCI supplementation. All the other enzymes showed optimum activity at 100 mM and declined further. Co-regulation of the nitrate uptake system and sequential enzyme activities plays a crucial role in governing the nitrogen status of strains during salt stress. HsIil0 experiencing minimum decline in enzyme activities and best possible nitrogen regulation under NaC1 replete condition showed adequate nutritional management. Among all the strains, HsIil0 proved to be salt tolerant on account of above features while the salt sensitive strain HsIi8 lacked the ability to regulate various steps of nitrogen metabolism during salinity, and thus Frankia strain HsIil0 can potentially serve as a potential biofertilizer in the saline soil. PMID:24772938

  6. β2-Adrenergic Receptor-Dependent Attenuation of Hypoxic Pulmonary Vasoconstriction Prevents Progression of Pulmonary Arterial Hypertension in Intermittent Hypoxic Rats

    PubMed Central

    Nagai, Hisashi; Kuwahira, Ichiro; Schwenke, Daryl O.; Tsuchimochi, Hirotsugu; Nara, Akina; Inagaki, Tadakatsu; Ogura, Sayoko; Fujii, Yutaka; Umetani, Keiji; Shimosawa, Tatsuo; Yoshida, Ken-ichi; Pearson, James T.; Uemura, Koichi; Shirai, Mikiyasu

    2014-01-01

    In sleep apnea syndrome (SAS), intermittent hypoxia (IH) induces repeated episodes of hypoxic pulmonary vasoconstriction (HPV) during sleep, which presumably contribute to pulmonary arterial hypertension (PAH). However, the prevalence of PAH was low and severity is mostly mild in SAS patients, and mild or no right ventricular hypertrophy (RVH) was reported in IH-exposed animals. The question then arises as to why PAH is not a universal finding in SAS if repeated hypoxia of sufficient duration causes cycling HPV. In the present study, rats underwent IH at a rate of 3 min cycles of 4–21% O2 for 8 h/d for 6w. Assessment of diameter changes in small pulmonary arteries in response to acute hypoxia and drugs were performed using synchrotron radiation microangiography on anesthetized rats. In IH-rats, neither PAH nor RVH was observed and HPV was strongly reversed. Nadolol (a hydrophilic β1, 2-blocker) augmented the attenuated HPV to almost the same level as that in N-rats, but atenolol (a hydrophilic β1-blocker) had no effect on the HPV in IH. These β-blockers had almost no effect on the HPV in N-rats. Chronic administration of nadolol during 6 weeks of IH exposure induced PAH and RVH in IH-rats, but did not in N-rats. Meanwhile, atenolol had no effect on morphometric and hemodynamic changes in N and IH-rats. Protein expression of the β1-adrenergic receptor (AR) was down-regulated while that of β2AR was preserved in pulmonary arteries of IH-rats. Phosphorylation of p85 (chief component of phosphoinositide 3-kinase (PI3K)), protein kinase B (Akt), and endothelial nitric oxide synthase (eNOS) were abrogated by chronic administration of nadolol in the lung tissue of IH-rats. We conclude that IH-derived activation of β2AR in the pulmonary arteries attenuates the HPV, thereby preventing progression of IH-induced PAH. This protective effect may depend on the β2AR-Gi mediated PI3K/Akt/eNOS signaling pathway. PMID:25350545

  7. Effect of dipeptidyl peptidase-4 inhibition on circadian blood pressure during the development of salt-dependent hypertension in rats

    PubMed Central

    Sufiun, Abu; Rafiq, Kazi; Fujisawa, Yoshihide; Rahman, Asadur; Mori, Hirohito; Nakano, Daisuke; Kobori, Hiroyuki; Ohmori, Koji; Masaki, Tsutomu; Kohno, Masakazu; Nishiyama, Akira

    2015-01-01

    A growing body of evidence has indicated that dipeptidyl peptidase-4 (DPP-4) inhibitors have antihypertensive effects. Here, we aim to examine the effect of vildagliptin, a DPP-4-specific inhibitor, on blood pressure and its circadian-dipping pattern during the development of salt-dependent hypertension in Dahl salt-sensitive (DSS) rats. DSS rats were treated with a high-salt diet (8% NaCl) plus vehicle or vildagliptin (3 or 10 mg kg−1 twice daily by oral gavage) for 7 days. Blood pressure was measured by the telemetry system. High-salt diet for 7 days significantly increased the mean arterial pressure (MAP), systolic blood pressure (SBP) and were also associated with an extreme dipping pattern of blood pressure in DSS rats. Treatment with vildagliptin dose-dependently decreased plasma DPP-4 activity, increased plasma glucagon-like peptide 1 (GLP-1) levels and attenuated the development of salt-induced hypertension. Furthermore, vildagliptin significantly increased urine sodium excretion and normalized the dipping pattern of blood pressure. In contrast, intracerebroventricular infusion of vildagliptin (50, 500 or 2500 μg) did not alter MAP and heart rate in DSS rats. These data suggest that salt-dependent hypertension initially develops with an extreme blood pressure dipping pattern. The DPP-4 inhibitor, vildagliptin, may elicit beneficial antihypertensive effects, including the improvement of abnormal circadian blood pressure pattern, by enhancing urinary sodium excretion. PMID:25588850

  8. Effect of dipeptidyl peptidase-4 inhibition on circadian blood pressure during the development of salt-dependent hypertension in rats.

    PubMed

    Sufiun, Abu; Rafiq, Kazi; Fujisawa, Yoshihide; Rahman, Asadur; Mori, Hirohito; Nakano, Daisuke; Kobori, Hiroyuki; Ohmori, Koji; Masaki, Tsutomu; Kohno, Masakazu; Nishiyama, Akira

    2015-04-01

    A growing body of evidence has indicated that dipeptidyl peptidase-4 (DPP-4) inhibitors have antihypertensive effects. Here, we aim to examine the effect of vildagliptin, a DPP-4-specific inhibitor, on blood pressure and its circadian-dipping pattern during the development of salt-dependent hypertension in Dahl salt-sensitive (DSS) rats. DSS rats were treated with a high-salt diet (8% NaCl) plus vehicle or vildagliptin (3 or 10 mg kg(-1) twice daily by oral gavage) for 7 days. Blood pressure was measured by the telemetry system. High-salt diet for 7 days significantly increased the mean arterial pressure (MAP), systolic blood pressure (SBP) and were also associated with an extreme dipping pattern of blood pressure in DSS rats. Treatment with vildagliptin dose-dependently decreased plasma DPP-4 activity, increased plasma glucagon-like peptide 1 (GLP-1) levels and attenuated the development of salt-induced hypertension. Furthermore, vildagliptin significantly increased urine sodium excretion and normalized the dipping pattern of blood pressure. In contrast, intracerebroventricular infusion of vildagliptin (50, 500 or 2500 μg) did not alter MAP and heart rate in DSS rats. These data suggest that salt-dependent hypertension initially develops with an extreme blood pressure dipping pattern. The DPP-4 inhibitor, vildagliptin, may elicit beneficial antihypertensive effects, including the improvement of abnormal circadian blood pressure pattern, by enhancing urinary sodium excretion. PMID:25588850

  9. Hypertension in Chronic Glomerulonephritis.

    PubMed

    Ihm, Chun-Gyoo

    2015-12-01

    Chronic glomerulonephritis (GN), which includes focal segmental glomerulosclerosis and proliferative forms of GN such as IgA nephropathy, increases the risk of hypertension. Hypertension in chronic GN is primarily volume dependent, and this increase in blood volume is not related to the deterioration of renal function. Patients with chronic GN become salt sensitive as renal damage including arteriolosclerosis progresses and the consequent renal ischemia causes the stimulation of the intrarenal renin-angiotensin-aldosterone system(RAAS). Overactivity of the sympathetic nervous system also contributes to hypertension in chronic GN. According to the KDIGO guideline, the available evidence indicates that the target BP should be ≤140mmHg systolic and ≤90mmHg diastolic in chronic kidney disease patients without albuminuria. In most patients with an albumin excretion rate of ≥30mg/24 h (i.e., those with both micro-and macroalbuminuria), a lower target of ≤130mmHg systolic and ≤80mmHg diastolic is suggested. The use of agents that block the RAAS system is recommended or suggested in all patients with an albumin excretion rate of ≥30mg/ 24 h. The combination of a RAAS blockade with a calcium channel blocker and a diuretic may be effective in attaining the target BP, and in reducing the amount of urinary protein excretion in patients with chronic GN. PMID:26848302

  10. Relationships between salt sensitivity of blood pressure and sympathetic nervous system activity: a short review of evidence.

    PubMed

    Strazzullo, P; Barbato, A; Vuotto, P; Galletti, F

    2001-01-01

    Experimental and clinical studies provided evidence in favor of complex relationships between sympathetic nervous system activity and salt-sensitivity of blood pressure. Genetic and acquired metabolic alterations associated with a tendency to retain salt and water may generate salt-sensitivity of blood pressure and shift the pressure-natriuresis curve to the right, promoting an increase in blood pressure. Sympathetic activation is a factor contributing to this result. Chronic high dietary salt intake is followed by a derangement in mechanisms of central sympathetic inhibition and then by an enhanced peripheral sympathetic tone. This, in turn, may generate salt-sensitivity of blood pressure by affecting renal hemodynamics, tubular sodium and water handling. Insulin resistance and sodium and water retention are prompted by high-fat (as well as high carbohydrate) diets, and by an increase in body fat mass. Also, aging is a condition of impaired interactions of the above factors. A gain in weight due to reduced physical activity, not followed by a parallel decrease in calorie intake, brings to a fall in insulin sensitivity. In many cases, the natural age-related decline of renal function is associated with a reduced physical exercise, hyperinsulinemia and sodium retention; sympathetic nervous system activity is enhanced and causes an increase in blood pressure. PMID:11270585

  11. Salt sensitivity in chickpea: Growth, photosynthesis, seed yield components and tissue ion regulation in contrasting genotypes.

    PubMed

    Khan, Hammad Aziz; Siddique, Kadambot H M; Munir, Rushna; Colmer, Timothy David

    2015-06-15

    Chickpea is a relatively salt sensitive species but shows genotypic variation for salt tolerance, measured as grain yield per plant in mild-to-moderately saline soil. This experiment was designed to evaluate some physiological responses to salinity in three contrasting genotypes. One tolerant (Genesis836), one moderately tolerant (JG11) and one sensitive (Rupali) genotype were grown for 108d in non-saline nutrient solution (controls) and two levels of salinity treatment (30 and 60mM NaCl). No plants survived to maturity in the 60mM NaCl treatment; however, Genesis836 survived longer (87d) than JG11 (67d) while Rupali died after 27d; only Genesis836 flowered, but no pods were filled. At 30mM NaCl, Genesis836 produced a few filled pods, whereas JG11 and Rupali did not. Genotypic differences in plant dry mass at the vegetative stage were evident only at 60mM NaCl, while at maturity differences were evident at 30mM NaCl. Photosynthesis was maintained to different degrees by the three genotypes (e.g. at 30mM NaCl, 35-81% of controls; highest in Genesis836); photosynthesis was restricted predominately due to non-stomatal limitations as the intercellular CO2 concentration was only modestly affected (94-99% of controls). Photosystem II damage was evident in the less tolerant genotypes (e.g. at 30mM NaCl, actual quantum efficiency of photosystem II values were 63-96% of controls). Across treatments, shoot dry mass was negatively correlated with both Na(+) and Cl(-) shoot concentrations. However, the sensitive genotype (Rupali) had equal or lower concentrations of these ions in green leaves, stems or roots compared to tolerant genotypes (JG11 and Genesis836); ion 'exclusion' does not explain variation for salt tolerance among these three chickpea genotypes. The large difference between Rupali (sensitive) and Genesis836 (tolerant) in the salt-induced reduction in net photosynthesis via non-stomatal limitations and the assessed damage to photosystem II, but with similar leaf

  12. Role of 20-HETE in the impaired myogenic and TGF responses of the Af-Art of Dahl salt-sensitive rats.

    PubMed

    Ge, Ying; Murphy, Sydney R; Fan, Fan; Williams, Jan Michael; Falck, John R; Liu, Ruisheng; Roman, Richard J

    2014-09-01

    The present study examined whether 20-HETE production is reduced in the renal vasculature and whether this impairs myogenic or tubuloglomerular feedback (TGF) responses of the afferent arteriole (Af-Art). The production of 20-HETE was 73% lower in renal microvessels of Dahl salt-sensitive rats (SS) rats than in SS.5(BN) rats, in which chromosome 5 from the Brown Norway (BN) rat containing the CYP4A genes was transferred into the SS genetic background. The luminal diameter of the Af-Art decreased by 14.7 ± 1.5% in SS.5(BN) rats when the perfusion pressure was increased from 60 to 120 mmHg, but it remained unaltered in SS rats. Administration of an adenosine type 1 receptor agonist (CCPA, 1 μM) reduced the diameter of the Af-Art in the SS.5(BN) rats by 44 ± 2%, whereas the diameter of the Af-Art of SS rats was unaltered. Autoregulation of renal blood flow (RBF) and glomerular capillary pressure (PGC) was significantly impaired in SS rats but was intact in SS.5(BN) rats. Administration of a 20-HETE synthesis inhibitor, HET0016 (1 μM), completely blocked the myogenic and adenosine responses in the Af-Art and autoregulation of RBF and PGC in SS.5(BN) rats, but it had no effect in SS rats. These data indicate that a deficiency in the formation of 20-HETE in renal microvessels impairs the reactivity of the Af-Art of SS rats and likely contributes to the development of hypertension induced renal injury. PMID:25007877

  13. A NOVEL AMILORIDE SENSITIVE H+ TRANSPORT PATHWAY MEDIATES ENHANCED SUPEROXIDE PRODUCTION IN THICK ASCENDING LIMB OF SALT-SENSITIVE RATS, NOT Na+/H+ EXCHANGE

    PubMed Central

    O’Connor, Paul M.; Lu, Limin; Liang, Mingyu; Cowley, Allen W.

    2009-01-01

    It has previously been reported that H+ efflux via Na+/H+ exchange stimulates NAD(P)H oxidase dependent O2 − production in medullary thick ascending limb. We have recently demonstrated that N-methyl-amiloride sensitive O2 − production is enhanced in thick ascending limb of salt-sensitive SS rats suggesting that H+ efflux through Na+/H+ exchangers may promote renal oxidative stress and the development of hypertension in these animals. In the current study we demonstrate, using selective and potent inhibitors, that inhibition of Na+/H+ exchange does not mediate the ability of N-methyl-amiloride to inhibit thick ascending limb O2 − production. To determine the mechanism of action of N-methyl-amiloride, we examined H+ efflux and O2 − production in SS and SS.13BN thick ascending limb of pre-hypertensive, 0.4% NaCl fed rats. Tissue strips containing medullary thick ascending limb were isolated from male SS and salt-resistant consomic SS.13BN rats, loaded with either DHE or BCECF, and imaged in a heated tissue bath. In Na+ replete media, activation of Na+/H+ exchange using an NH4Cl prepulse did not stimulate thick ascending limb O2 −production. In Na+ free media containing BaCl2 in which Na+/H+ activity was inhibited, a NH4Cl pre-pulse stimulated mTAL O2 −. This response was enhanced in mTAL of SS rats (slope ΔEth/ΔDHE=0.029±0.004) compared to SS.13BN rats (slope=0.010±0.004; p<0.04) and could be inhibited by N-methyl-amiloride (slope=0.005±0.002 & 0.006±0.002 for SS and SS.13BN, respectively). We conclude that only H+ efflux through a specific, as yet unidentified, amiloride-sensitive H+ channel promotes O2 − production in medullary thick ascending limb, and that this channel is up-regulated in SS rats. PMID:19564541

  14. A complex network analysis of hypertension-related genes

    NASA Astrophysics Data System (ADS)

    Wang, Huan; Xu, Chuan-Yun; Hu, Jing-Bo; Cao, Ke-Fei

    2014-01-01

    In this paper, a network of hypertension-related genes is constructed by analyzing the correlations of gene expression data among the Dahl salt-sensitive rat and two consomic rat strains. The numerical calculations show that this sparse and assortative network has small-world and scale-free properties. Further, 16 key hub genes (Col4a1, Lcn2, Cdk4, etc.) are determined by introducing an integrated centrality and have been confirmed by biological/medical research to play important roles in hypertension.

  15. Key Points of the Japanese Society of Hypertension Guidelines for the Management of Hypertension in 2014

    PubMed Central

    Kario, Kazuomi

    2015-01-01

    The Japanese Society of Hypertension (JSH) published the new JSH guidelines for the management of hypertension in 2014, which is the revision of the JSH guidelines of 2009. The primary objective of the guideline is to provide physicians the standard treatment strategy of hypertension to prevent the hypertension-related target organ damage and cardiovascular events. The management of hypertension should be performed in hypertensive patients with a blood pressure of ≥140/90 mm Hg. As Asians have a higher prevalence of stroke than of coronary artery disease and stroke is more steeply associated with the level of blood pressure, the target blood pressure should be lower than 130/80 mm Hg for high-risk patients such as those with diabetes or chronic kidney disease. Because of the increasing prevalence of obesity and the related metabolic syndrome, more salt intake and higher salt sensitivity in the population, lifestyle modifications are necessary in hypertensive patients and subjects with high normal blood pressure. This guideline provides evidence-based recommendations for the management of patients with hypertension with the characteristics of our society. PMID:26587456

  16. [Secondary hypertension].

    PubMed

    Yoshida, Yuichi; Shibata, Hirotaka

    2015-11-01

    Hypertension is a common disease and a crucial predisposing factor of cardiovascular diseases. Approximately 10% of hypertensive patients are secondary hypertension, a pathogenetic factor of which can be identified. Secondary hypertension consists of endocrine, renal, and other diseases. Primary aldosteronism, Cushing's syndrome, pheochromocytoma, hyperthyroidism, and hypothyroidism result in endocrine hypertension. Renal parenchymal hypertension and renovascular hypertension result in renal hypertension. Other diseases such as obstructive sleep apnea syndrome are also very prevalent in secondary hypertension. It is very crucial to find and treat secondary hypertension at earlier stages since most secondary hypertension is curable or can be dramatically improved by specific treatment. One should keep in mind that screening of secondary hypertension should be done at least once in a daily clinical practice. PMID:26619670

  17. Portal Hypertension

    MedlinePlus

    ... Chronic Hepatitis C Additional Content Medical News Portal Hypertension By Steven K. Herrine, MD NOTE: This is ... Hepatic Encephalopathy Jaundice in Adults Liver Failure Portal Hypertension Portal hypertension is abnormally high blood pressure in ...

  18. Synthesis, characterization, and swelling behaviors of salt-sensitive maize bran-poly(acrylic acid) superabsorbent hydrogel.

    PubMed

    Zhang, Mingyue; Cheng, Zhiqiang; Zhao, Tianqi; Liu, Mengzhu; Hu, Meijuan; Li, Junfeng

    2014-09-01

    A novel composite hydrogel was prepared via UV irradiation copolymerization of acrylic acid and maize bran (MB) in the presence of composite initiator (2,2-dimethoxy-2-phenylacetophenone and ammonium persulfate) and cross-linker (N,N'-methylenebis(acrylamide)). Under the optimized conditions, maize bran-poly(acrylic acid) was obtained (2507 g g(-1) in distilled water and 658 g g(-1) in 0.9 wt % NaCl solution). Effects of granularity, salt concentration, and various cations and anions on water absorbency were investigated. It was found that swelling was extremely sensitive to the ionic strength and cation and anion type. Swelling kinetics and water diffusion mechanism in distilled water were also discussed. Moreover, the product showed excellent water retention capability under the condition of high temperature or high pressure. The salt sensitivity, good water absorbency, and excellent water retention capability of the hydrogels give this intelligentized polymer wide potential applications. PMID:25133321

  19. Effects of Aged Garlic Extract on Left Ventricular Diastolic Function and Fibrosis in a Rat Hypertension Model

    PubMed Central

    Hara, Yuki; Noda, Akiko; Miyata, Seiko; Minoshima, Makoto; Sugiura, Mari; Kojima, Jun; Otake, Masafumi; Furukawa, Mayuko; Cheng, Xian Wu; Nagata, Kohzo; Murohara, Toyoaki

    2013-01-01

    Daily consumption of garlic is known to lower the risk of hypertension and ischemic heart disease. In this study, we examined whether aged garlic extract (AGE) prevents hypertension and the progression of compensated left ventricular (LV) hypertrophy in Dahl salt-sensitive (DS) rats. DS rats were randomly divided into three groups: those fed an 8% NaCl diet until 18 weeks of age (8% NaCl group), those additionally treated with AGE (8% NaCl + AGE group), and control rats maintained on a diet containing 0.3% NaCl until 18 weeks of age (0.3% NaCl group). AGE was administered orally by gastric gavage once a day until 18 weeks of age. LV mass was significantly higher in the 8% NaCl + AGE group than in the 0.3% NaCl group at 18 weeks of age, but significantly lower in the 8% NaCl + AGE group than in the 8% NaCl group. No significant differences were observed in systolic blood pressure (SBP) between the 8% NaCl and 8% NaCl + AGE groups at 12 and 18 weeks of age. LV end-diastolic pressure and pressure half-time at 12 and 18 weeks of age were significantly lower in the 8% NaCl + AGE group compared with the 8% NaCl group. AGE significantly reduced LV interstitial fibrosis at 12 and 18 weeks of age. Chronic AGE intake attenuated LV diastolic dysfunction and fibrosis without significantly decreasing SBP in hypertensive DS rats. PMID:24172194

  20. Effects of aged garlic extract on left ventricular diastolic function and fibrosis in a rat hypertension model.

    PubMed

    Hara, Yuki; Noda, Akiko; Miyata, Seiko; Minoshima, Makoto; Sugiura, Mari; Kojima, Jun; Otake, Masafumi; Furukawa, Mayuko; Cheng, Xian Wu; Nagata, Kohzo; Murohara, Toyoaki

    2013-01-01

    Daily consumption of garlic is known to lower the risk of hypertension and ischemic heart disease. In this study, we examined whether aged garlic extract (AGE) prevents hypertension and the progression of compensated left ventricular (LV) hypertrophy in Dahl salt-sensitive (DS) rats. DS rats were randomly divided into three groups: those fed an 8% NaCl diet until 18 weeks of age (8% NaCl group), those additionally treated with AGE (8% NaCl + AGE group), and control rats maintained on a diet containing 0.3% NaCl until 18 weeks of age (0.3% NaCl group). AGE was administered orally by gastric gavage once a day until 18 weeks of age. LV mass was significantly higher in the 8% NaCl + AGE group than in the 0.3% NaCl group at 18 weeks of age, but significantly lower in the 8% NaCl + AGE group than in the 8% NaCl group. No significant differences were observed in systolic blood pressure (SBP) between the 8% NaCl and 8% NaCl + AGE groups at 12 and 18 weeks of age. LV end-diastolic pressure and pressure half-time at 12 and 18 weeks of age were significantly lower in the 8% NaCl + AGE group compared with the 8% NaCl group. AGE significantly reduced LV interstitial fibrosis at 12 and 18 weeks of age. Chronic AGE intake attenuated LV diastolic dysfunction and fibrosis without significantly decreasing SBP in hypertensive DS rats. PMID:24172194

  1. The Expression of Millettia pinnata Chalcone Isomerase in Saccharomyces cerevisiae Salt-Sensitive Mutants Enhances Salt-Tolerance

    PubMed Central

    Wang, Hui; Hu, Tangjin; Huang, Jianzi; Lu, Xiang; Huang, Baiqu; Zheng, Yizhi

    2013-01-01

    The present study demonstrates a new Millettia pinnata chalcone isomerase (MpCHI) whose transcription level in leaf was confirmed to be enhanced after being treated by seawater or NaCl (500 mM) via transcriptome sequencing and Real-Time Quantitative Reverse Transcription PCR (QRT-PCR) analyses. Its full length cDNA (666 bp) was obtained by 3′-end and 5′-end Rapid Amplification of cDNA Ends (RACE). The analysis via NCBI BLAST indicates that both aminoacid sequence and nucleotide sequence of the MpCHI clone share high homology with other leguminous CHIs (73%–86%). Evolutionarily, the phylogenic analysis further revealed that the MpCHI is a close relative of leguminous CHIs. The MpCHI protein consists of 221 aminoacid (23.64 KDa), whose peptide length, amino acid residues of substrate-binding site and reactive site are very similar to other leguminous CHIs reported previously. Two pYES2-MpCHI transformed salt-sensitive Saccharomyces cerevisiae mutants (Δnha1 and Δnhx1) showed improved salt-tolerance significantly compared to pYES2-vector transformed yeast mutants, suggesting the MpCHI or the flavonoid biosynthesis pathway could regulate the resistance to salt stress in M. pinnata. PMID:23615469

  2. Effects of L/N-type calcium channel antagonist, cilnidipine on progressive renal injuries in Dahl salt-sensitive rats.

    PubMed

    Konda, Tomoyuki; Enomoto, Azusa; Takahara, Akira; Yamamoto, Hiroshi

    2006-05-01

    The sympathetic nerve activity plays an important role on the renal function through the vasoactive system and the renin-angiotensin system. Although interest in the renal protective effects of anti-sympathetic agents has been increased, there are not enough data to clarify this efficiency. Therefore, we investigated the effects of L/N-type calcium channel antagonist, cilnidipine on progressive renal injury in Dahl salt-sensitive (Dahl S) rats. Male Dahl S rats (6 weeks of age) were fed a high salt (4% NaCl) diet. They were divided into groups with similar blood pressure at 12 weeks of age and they received vehicle (n=7) or cilnidipine (30 mg/kg/d as food admix, n=9) for 8 weeks. Cilnidipine treatment suppressed the increase in systolic blood pressure. Although urinary protein excretion was not influenced, cilnidipine inhibited the increase in blood urea nitrogen and decrease in creatinine clearance. Histological investigation revealed that progression of glomerular sclerosis was inhibited in cilnidipine treatment group. Of notes, cilnidipine reduced plasma norepinephrine level and plasma rennin activity compared with vehicle-treated Dahl S rats. These data indicated that cilnidipine has suppressive effects against progressive renal injury in Dahl S rats. This effect is not only explained by the L-type calcium channel blocking action that lowered blood pressure, but also partially explained by the N-type calcium channel blocking action that lead to suppression of the sympathetic nerve activity and renin-angiotensin system. PMID:16651722

  3. Vascular and Central Activation of Peroxisome Proliferator-Activated Receptor-β Attenuates Angiotensin II-Induced Hypertension: Role of RGS-5.

    PubMed

    Romero, Miguel; Jiménez, Rosario; Toral, Marta; León-Gómez, Elvira; Gómez-Gúzman, Manuel; Sánchez, Manuel; Zarzuelo, María José; Rodríguez-Gómez, Isabel; Rath, Geraldine; Tamargo, Juan; Pérez-Vizcaíno, Francisco; Dessy, Chantal; Duarte, Juan

    2016-07-01

    Activation of peroxisome proliferator-activated receptor-β/δ (PPARβ) lowers blood pressure in genetic and mineralocorticoid-induced hypertension. Regulator of G-protein-coupled receptor signaling 5 (RGS5) protein, which interferes in angiotensin II (AngII) signaling, is a target gene to PPARβ The aim of the present study was to examine whether PPARβ activation in resistance arteries and brain tissues prevents the elevated blood pressure in AngII-induced hypertension and evaluate the role of RGS5 in this effect. C57BL/6J male mice were divided into five groups (control mice, PPARβ agonist [4-[[[2-[3-Fluoro-4-(trifluoromethyl)phenyl]-4-methyl-5-thiazolyl]methyl]thio]-2-methylphenoxy]acetic acid (GW0742)-treated mice AngII-infused mice, GW0742-treated AngII-infused mice, and AngII-infused mice treated with GW0742 plus PPARβ antagonist 3-[[[2-Methoxy-4-(phenylamino)phenyl]amino]sulfonyl]-2-thiophenecarboxylic acid methyl ester (GSK0660)) and were followed for 3 weeks. GW0742 prevented the increase in both arterial blood pressure and plasma noradrenaline levels and the higher reduction of blood pressure after ganglionic blockade, whereas it reduced the mesenteric arterial remodeling and the hyper-responsiveness to vasoconstrictors (AngII and endothelin-1) in AngII-infused mice. These effects were accompanied by an inhibition of NADPH oxidase expression and activity in the brain. Gene expression profiling revealed a marked loss of brainstem and vascular RGS5 in AngII-infused mice, which was restored by GW0742. GW0742-induced effects were abolished by GSK0660. Small interfering RNA targeting RGS5 caused augmented contractile response to AngII in resistance mesenteric arteries and blunted the inhibitory effect of GW0742 on this response. In conclusion, GW0742 exerted antihypertensive effects, restoring sympathetic tone and vascular structure and function in AngII-infused mice by PPARβ activation in brain and vessels inhibiting AngII signaling as a result of RGS5

  4. Renovascular hypertension

    MedlinePlus

    Renal hypertension; Hypertension - renovascular; Renal artery occlusion; Stenosis - renal artery; Renal artery stenosis ... Renal artery stenosis is a narrowing or blockage of the arteries that supply blood to the kidneys. The most ...

  5. Hypertension - overview

    MedlinePlus Videos and Cool Tools

    If left untreated, hypertension can lead to the thickening of arterial walls causing its lumen, or blood passage way, to narrow in diameter. ... the narrowed arterial openings. In addition, people with hypertension may be more susceptible to stroke.

  6. Renovascular hypertension

    MedlinePlus

    Renal hypertension; Hypertension - renovascular; Renal artery occlusion; Stenosis - renal artery; Renal artery stenosis ... blood pressure to rise. Risk factors for atherosclerosis: High blood pressure Smoking Diabetes High cholesterol Heavy alcohol use Cocaine ...

  7. Hemoglobin-induced lung vascular oxidation, inflammation, and remodeling contribute to the progression of hypoxic pulmonary hypertension and is attenuated in rats with repeated-dose haptoglobin administration.

    PubMed

    Irwin, David C; Baek, Jin Hyen; Hassell, Kathryn; Nuss, Rachelle; Eigenberger, Paul; Lisk, Christina; Loomis, Zoe; Maltzahn, Joanne; Stenmark, Kurt R; Nozik-Grayck, Eva; Buehler, Paul W

    2015-05-01

    Haptoglobin (Hp) is an approved treatment in Japan for trauma, burns, and massive transfusion-related hemolysis. Additional case reports suggest uses in other acute hemolytic events that lead to acute kidney injury. However, Hp's protective effects on the pulmonary vasculature have not been evaluated within the context of mitigating the consequences of chronic hemoglobin (Hb) exposure in the progression of pulmonary hypertension (PH) secondary to hemolytic diseases. This study was performed to assess the utility of chronic Hp therapy in a preclinical model of Hb and hypoxia-mediated PH. Rats were simultaneously exposed to chronic Hb infusion (35 mg per day) and hypobaric hypoxia for 5 weeks in the presence or absence of Hp treatment (90 mg/kg twice a week). Hp inhibited the Hb plus hypoxia-mediated nonheme iron accumulation in lung and heart tissue, pulmonary vascular inflammation and resistance, and right-ventricular hypertrophy, which suggests a positive impact on impeding the progression of PH. In addition, Hp therapy was associated with a reduction in critical mediators of PH, including lung adventitial macrophage population and endothelial ICAM-1 expression. By preventing Hb-mediated pathology, Hp infusions: (1) demonstrate a critical role for Hb in vascular remodeling associated with hypoxia and (2) suggest a novel therapy for chronic hemolysis-associated PH. PMID:25656991

  8. Hemoglobin induced lung vascular oxidation, inflammation, and remodeling contributes to the progression of hypoxic pulmonary hypertension and is attenuated in rats with repeat dose haptoglobin administration

    PubMed Central

    Baek, Jin Hyen; Hassell, Kathryn; Nuss, Rachelle; Eigenberger, Paul; Lisk, Christina; Loomis, Zoe; Maltzahn, Joanne; Stenmark, Kurt R; Nozik-Grayck, Eva

    2015-01-01

    Objective Haptoglobin (Hp) is an approved treatment in Japan with indications for trauma, burns and massive transfusion related hemolysis. Additional case reports suggest uses in other acute hemolytic events that lead to acute kidney injury. However, Hp's protective effects on the pulmonary vasculature have not been evaluated within the context of mitigating the consequences of chronic hemoglobin (Hb) exposure in the progression of pulmonary hypertension (PH) secondary to hemolytic diseases. This study was performed to assess the utility of chronic Hp therapy in a preclinical model of Hb and hypoxia mediated PH. Approach and results Rats were simultaneously exposed to chronic Hb-infusion (35 mg per day) and hypobaric hypoxia for five weeks in the presence or absence of Hp treatment (90 mg/kg twice a week). Hp inhibited the Hb plus hypoxia-mediated non-heme iron accumulation in lung and heart tissue, pulmonary vascular inflammation and resistance, and right ventricular hypertrophy, which suggest a positive impact on impeding the progression of PH. In addition, Hp therapy was associated with a reduction in critical mediators of PH, including lung adventitial macrophage population and endothelial ICAM-1 expression. Conclusions By preventing Hb-mediated pathology, Hp infusions: (1) demonstrate a critical role for Hb in vascular remodeling associated with hypoxia; and (2) suggest a novel therapy for chronic hemolysis associated PH. PMID:25656991

  9. Hypertension in Cardiovascular and Kidney Disease

    PubMed Central

    Botdorf, Joshua; Chaudhary, Kunal; Whaley-Connell, Adam

    2011-01-01

    The relationship between hypertension and chronic kidney disease (CKD) is bidirectional in nature and, generally, management strategies for cardiovascular risk reduction also attenuate progression of CKD. Prevalent hypertension increases with diminishing kidney function, and the management strategy changes with level of kidney function. In this review, we will examine the evidence for management of hypertension, as a modifiable risk factor for cardiovascular disease in CKD, and the impact of this management on progression of CKD. PMID:22096454

  10. Divergences in morphological changes and antioxidant responses in salt-tolerant and salt-sensitive rice seedlings after salt stress.

    PubMed

    Lee, Min Hee; Cho, Eun Ju; Wi, Seung Gon; Bae, Hyoungwoo; Kim, Ji Eun; Cho, Jae-Young; Lee, Sungbeom; Kim, Jin-Hong; Chung, Byung Yeoup

    2013-09-01

    Salinization plays a primary role in soil degradation and reduced agricultural productivity. We observed that salt stress reversed photosynthesis and reactive oxygen scavenging responses in leaves or roots of two rice cultivars, a salt-tolerant cultivar Pokkali and a salt-sensitive cultivar IR-29. Salt treatment (100 mM NaCl) on IR-29 decreased the maximum photochemical efficiency (Fv/Fm) and the photochemical quenching coefficient (qP), thereby inhibiting photosynthetic activity. By contrast, the salt treatment on Pokkali had the converse effect on Fv/Fm and qP, while increasing the nonphotochemical quenching coefficient (NPQ), thereby favoring photosynthetic activity. Notably, chloroplast or root cells in Pokkali maintained their ultrastructures largely intact under the salt stress, but, IR-29 showed severe disintegration of existing grana stacks, increase of plastoglobuli, and swelling of thylakoidal membranes in addition to collapsed vascular region in adventitious roots. Pokkali is known to have higher hydrogen peroxide (H2O2)-scavenging enzyme activities in non-treated seedlings, including ascorbate peroxidase, catalase, and peroxidase activities. However, these enzymatic activities were induced to a greater extent in IR-29 by the salt stress. While the level of endogenous H2O2 was lower in Pokkali than in IR-29, it was reversed upon the salt treatment. Nevertheless, the decreased amount of H2O2 in IR-29 upon the salt stress didn't result in a high scavenging activity of total cell extracts for H2O2, as well as O2(·-) and (·)OH species. The present study suggests that the tolerance to the moderate salinity in Pokkali derives largely from the constitutively maintained antioxidant enzymatic activities as well as the induced antioxidant enzyme system. PMID:23811121

  11. Losartan attenuates chronic cigarette smoke exposure-induced pulmonary arterial hypertension in rats: Possible involvement of angiotensin-converting enzyme-2

    SciTech Connect

    Han Suxia; He Guangming; Wang Tao; Chen Lei; Ning Yunye; Luo Feng; An Jin; Yang Ting; Dong Jiajia; Liao Zenglin; Xu Dan; Wen Fuqiang

    2010-05-15

    Chronic cigarette smoking induces pulmonary arterial hypertension (PAH) by largely unknown mechanisms. Renin-angiotensin system (RAS) is known to function in the development of PAH. Losartan, a specific angiotensin II receptor antagonist, is a well-known antihypertensive drug with a potential role in regulating angiotensin-converting enzyme-2 (ACE2), a recently found regulator of RAS. To determine the effect of losartan on smoke-induced PAH and its possible mechanism, rats were daily exposed to cigarette smoke for 6 months in the absence and in the presence of losartan. Elevated right ventricular systolic pressure (RVSP), thickened wall of pulmonary arteries with apparent medial hypertrophy along with increased angiotensin II (Ang II) and decreased ACE2 levels were observed in smoke-exposed-only rats. Losartan administration ameliorated pulmonary vascular remodeling, inhibited the smoke-induced RVSP and Ang II elevation and partially reversed the ACE2 decrease in rat lungs. In cultured primary pulmonary artery smooth muscle cells (PASMCs) from 3- and 6-month smoke-exposed rats, ACE2 levels were significantly lower than in those from the control rats. Moreover, PASMCs from 6-month exposed rats proliferated more rapidly than those from 3-month exposed or control rats, and cells grew even more rapidly in the presence of DX600, an ACE2 inhibitor. Consistent with the in vivo study, in vitro losartan pretreatment also inhibited cigarette smoke extract (CSE)-induced cell proliferation and ACE2 reduction in rat PASMCs. The results suggest that losartan may be therapeutically useful in the chronic smoking-induced pulmonary vascular remodeling and PAH and ACE2 may be involved as part of its mechanism. Our study might provide insight into the development of new therapeutic interventions for PAH smokers.

  12. [Childhood hypertension].

    PubMed

    Takemura, Tsukasa

    2015-11-01

    For accurate diagnosis of childhood hypertension, selection of appropriate manchette size according to the child age and the circumstantial size of upper limb is essentially important. In addition, except for the emergency case of hypertension, repeated measurement of blood pressure would be desirable in several weeks interval. Recently, childhood hypertension might be closely related to the abnormality of maternal gestational period caused by the strict diet and the maternal smoking. Developmental Origins of Health and Disease(DOHaD) theory is now highlighted in the pathogenesis of adulthood hypertension. To prevent hypertension of small-for-date baby in later phase of life, maternal education for child nursing should be conducted. In children, secondary hypertension caused by renal, endocrinologic, or malignant disease is predominant rather than idiopathic hypertension. PMID:26619664

  13. Resistant Hypertension.

    PubMed

    Doroszko, Adrian; Janus, Agnieszka; Szahidewicz-Krupska, Ewa; Mazur, Grzegorz; Derkacz, Arkadiusz

    2016-01-01

    Resistant hypertension is a severe medical condition which is estimated to appear in 9-18% of hypertensive patients. Due to higher cardiovascular risk, this disorder requires special diagnosis and treatment. The heterogeneous etiology, risk factors and comorbidities of resistant hypertension stand in need of sophisticated evaluation to confirm the diagnosis and select the best therapeutic options, which should consider lifestyle modifications as well as pharmacological and interventional treatment. After having excluded pseudohypertension, inappropriate blood pressure measurement and control as well as the white coat effect, suspicion of resistant hypertension requires an analysis of drugs which the hypertensive patient is treated with. According to one definition - ineffective treatment with 3 or more antihypertensive drugs including diuretics makes it possible to diagnose resistant hypertension. A multidrug therapy including angiotensin - converting enzyme inhibitors, angiotensin II receptor blockers, beta blockers, diuretics, long-acting calcium channel blockers and mineralocorticoid receptor antagonists has been demonstrated to be effective in resistant hypertension treatment. Nevertheless, optional, innovative therapies, e.g. a renal denervation or baroreflex activation, may create a novel pathway of blood pressure lowering procedures. The right diagnosis of this disease needs to eliminate the secondary causes of resistant hypertension e.g. obstructive sleep apnea, atherosclerosis and renal or hormonal disorders. This paper briefly summarizes the identification of the causes of resistant hypertension and therapeutic strategies, which may contribute to the proper diagnosis and an improvement of the long term management of resistant hypertension. PMID:26935512

  14. Narrowing a region on rat chromosome 13 that protects against hypertension in Dahl SS-13BN congenic strains.

    PubMed

    Moreno, Carol; Williams, Jan M; Lu, Limin; Liang, Mingyu; Lazar, Jozef; Jacob, Howard J; Cowley, Allen W; Roman, Richard J

    2011-04-01

    Transfer of chromosome 13 from the Brown Norway (BN) rat onto the Dahl salt-sensitive (SS) genetic background attenuates the development of hypertension, but the genes involved remain to be identified. The purpose of the present study was to confirm by telemetry that a congenic strain [SS.BN-(D13Hmgc37-D13Got22)/Mcwi, line 5], carrying a 13.4-Mb segment of BN chromosome 13 from position 32.4 to 45.8 Mb, is protected from the development of hypertension and then to narrow the region of interest by creating and phenotyping 11 additional subcongenic strains. Mean arterial pressure (MAP) rose from 118 ± 1 to 186 ± 5 mmHg in SS rats fed a high-salt diet (8.0% NaCl) for 3 wk. Protein excretion increased from 56 ± 11 to 365 ± 37 mg/day. In contrast, MAP only increased to 152 ± 9 mmHg in the line 5 congenic strain. Six subcongenic strains carrying segments of BN chromosome 13 from 32.4 and 38.2 Mb and from 39.9 to 45.8 Mb were not protected from the development of hypertension. In contrast, MAP was reduced by ∼30 mmHg in five strains, carrying a 1.9-Mb common segment of BN chromosome 13 from 38.5 to 40.4 Mb. Proteinuria was reduced by ∼50% in these strains. Sequencing studies did not identify any nonsynonymous single nucleotide polymorphisms in the coding region of the genes in this region. RT-PCR studies indicated that 4 of the 13 genes in this region were differentially expressed in the kidney of two subcongenic strains that were partially protected from hypertension vs. those that were not. These results narrow the region of interest on chromosome 13 from 13.4 Mb (159 genes) to a 1.9-Mb segment containing only 13 genes, of which 4 are differentially expressed in strains partially protected from the development of hypertension. PMID:21257920

  15. Candidate genes for hypertension: insights from the Dahl S rat.

    PubMed

    Rudemiller, Nathan P; Mattson, David L

    2015-12-15

    Human genetic linkage and association studies have nominated many genes as possible contributors to disease. Mutating or deleting these genes in a relevant disease model can validate their association with disease and potentially uncover novel mechanisms of pathogenesis. Targeted genetic mutagenesis has only recently been developed in the rat, and this technique has been applied in the Dahl salt-sensitive (S) rat to investigate human candidate genes associated with hypertension. This mini-review communicates the findings of these studies and displays how targeted genetic mutagenesis may contribute to the discovery of novel therapies for patients. PMID:25877508

  16. Genome-Wide Gene-Sodium Interaction Analyses on Blood Pressure: The Genetic Epidemiology Network of Salt-Sensitivity Study.

    PubMed

    Li, Changwei; He, Jiang; Chen, Jing; Zhao, Jinying; Gu, Dongfeng; Hixson, James E; Rao, Dabeeru C; Jaquish, Cashell E; Gu, Charles C; Chen, Jichun; Huang, Jianfeng; Chen, Shufeng; Kelly, Tanika N

    2016-08-01

    We performed genome-wide analyses to identify genomic loci that interact with sodium to influence blood pressure (BP) using single-marker-based (1 and 2 df joint tests) and gene-based tests among 1876 Chinese participants of the Genetic Epidemiology Network of Salt-Sensitivity (GenSalt) study. Among GenSalt participants, the average of 3 urine samples was used to estimate sodium excretion. Nine BP measurements were taken using a random zero sphygmomanometer. A total of 2.05 million single-nucleotide polymorphisms were imputed using Affymetrix 6.0 genotype data and the Chinese Han of Beijing and Japanese of Tokyo HapMap reference panel. Promising findings (P<1.00×10(-4)) from GenSalt were evaluated for replication among 775 Chinese participants of the Multi-Ethnic Study of Atherosclerosis (MESA). Single-nucleotide polymorphism and gene-based results were meta-analyzed across the GenSalt and MESA studies to determine genome-wide significance. The 1 df tests identified interactions for UST rs13211840 on diastolic BP (P=3.13×10(-9)). The 2 df tests additionally identified associations for CLGN rs2567241 (P=3.90×10(-12)) and LOC105369882 rs11104632 (P=4.51×10(-8)) with systolic BP. The CLGN variant rs2567241 was also associated with diastolic BP (P=3.11×10(-22)) and mean arterial pressure (P=2.86×10(-15)). Genome-wide gene-based analysis identified MKNK1 (P=6.70×10(-7)), C2orf80 (P<1.00×10(-12)), EPHA6 (P=2.88×10(-7)), SCOC-AS1 (P=4.35×10(-14)), SCOC (P=6.46×10(-11)), CLGN (P=3.68×10(-13)), MGAT4D (P=4.73×10(-11)), ARHGAP42 (P≤1.00×10(-12)), CASP4 (P=1.31×10(-8)), and LINC01478 (P=6.75×10(-10)) that were associated with at least 1 BP phenotype. In summary, we identified 8 novel and 1 previously reported BP loci through the examination of single-nucleotide polymorphism and gene-based interactions with sodium. PMID:27271309

  17. Malignant hypertension

    MedlinePlus

    ... Lippincott Williams & Wilkins; 2009:chap 89. Read More Acute kidney failure Alertness - decreased Angina Heart attack Preeclampsia Pulmonary edema Renovascular hypertension Seizures Stroke Update ...

  18. Mineralocorticoid hypertension

    PubMed Central

    Gupta, Vishal

    2011-01-01

    Hypertension affects about 10 – 25% of the population and is an important risk factor for cardiovascular and renal disease. The renin-angiotensin system is frequently implicated in the pathophysiology of hypertension, be it primary or secondary. The prevalence of primary aldosteronism increases with the severity of hypertension, from 2% in patients with grade 1 hypertension to 20% among resistant hypertensives. Mineralcorticoid hypertension includes a spectrum of disorders ranging from renin-producing pathologies (renin-secreting tumors, malignant hypertension, coarctation of aorta), aldosterone-producing pathologies (primary aldosteronism – Conns syndrome, familial hyperaldosteronism 1, 2, and 3), non-aldosterone mineralocorticoid producing pathologies (apparent mineralocorticoid excess syndrome, Liddle syndrome, deoxycorticosterone-secreting tumors, ectopic adrenocorticotropic hormones (ACTH) syndrome, congenitalvadrenal hyperplasia), and drugs with mineraocorticoid activity (locorice, carbenoxole therapy) to glucocorticoid receptor resistance syndromes. Clinical presentation includes hypertension with varying severity, hypokalemia, and alkalosis. Ratio of plasma aldosterone concentraion to plasma renin activity remains the best screening tool. Bilateral adrenal venous sampling is the best diagnostic test coupled with a CT scan. Treatment is either surgical (adrenelectomy) for unilateral adrenal disease versus medical therapy for idiopathic, ambiguous, or bilateral disease. Medical therapy focuses on blood pressure control and correction of hypokalemia using a combination of anti-hypertensives (calcium channel blockers, angiotensin converting enzyme inhibitors, or angiotensin receptor blockers) and potassium-raising therapies (mineralcorticoid receptor antagonist or potassium sparing diuretics). Direct aldosterone synthetase antagonists represent a promising future therapy. PMID:22145132

  19. Allelic Variants in Arhgef11 via the Rho-Rock Pathway Are Linked to Epithelial–Mesenchymal Transition and Contributes to Kidney Injury in the Dahl Salt-Sensitive Rat

    PubMed Central

    Jia, Zhen; Johnson, Ashley C.; Wang, Xuexiang; Guo, Zibiao; Dreisbach, Albert W.; Lewin, Jack R.; Kyle, Patrick B.; Garrett, Michael R.

    2015-01-01

    Previously, genetic analyses identified that variants in Arhgef11 may influence kidney injury in the Dahl salt-sensitive (S) rat, a model of hypertensive chronic kidney disease. To understand the potential mechanism by which altered expression and/or protein differences in Arhgef11 could play a role in kidney injury, stably transduced Arhgef11 knockdown cell lines as well as primary cultures of proximal tubule cells were studied. Genetic knockdown of Arhgef11 in HEK293 and NRK resulted in reduced RhoA activity, decreased activation of Rho-ROCK pathway, and less stress fiber formation versus control, similar to what was observed by pharmacological inhibition (fasudil). Primary proximal tubule cells (PTC) cultured from the S exhibited increased expression of Arhgef11, increased RhoA activity, and up regulation of Rho-ROCK signaling compared to control (small congenic). The cells were also more prone (versus control) to TGFβ-1 induced epithelial-mesenchymal transition (EMT), a hallmark feature of the development of renal interstitial fibrosis, and characterized by development of spindle shape morphology, gene expression changes in EMT markers (Col1a3, Mmp9, Bmp7, and Ocln) and increased expression of N-Cadherin and Vimentin. S derived PTC demonstrated a decreased ability to uptake FITC-albumin compared to the small congenic in vitro, which was confirmed by assessment of albumin re-uptake in vivo by infusion of FITC-albumin and immunofluorescence imaging. In summary, these studies suggest that genetic variants in the S form of Arhgef11 via increased expression and/or protein activity play a role in promoting kidney injury in the S rat through changes in cell morphology (Rho-Rock and/or EMT) that impact the function of tubule cells. PMID:26172442

  20. [Resistant hypertension].

    PubMed

    Feldstein, Carlos A

    2008-04-01

    Resistant hypertension, defined as a persistent blood pressure over 140/90 mmHg despite the use of three antihypertensive drugs including a diuretic, is unusual. The diagnosis requires ruling out initially pseudoresistance and a lack of compliance with treatment. Ambulatory blood pressure recording allow the recognition of white coat hypertension. When there is a clinical or laboratory suspicion, secondary causes of hypertension should be discarded. Excessive salt intake, the presence of concomitant diseases such as diabetes mellitus, chronic renal disease, obesity, and psychiatric conditions such as panic attacks, anxiety and depression, should also be sought. The presence of target organ damage requires a more aggressive treatment of hypertension. Recent clinical studies indicate that the administration of aldosterone antagonists as a fourth therapeutic line provides significant additional blood pressure reduction, when added to previous antihypertensive regimens in subjects with resistant hypertension. The possible blood pressure lowering effects of prolonged electrical activation of carotid baroreceptors is under investigation. PMID:18769797

  1. Hypertensive crisis.

    PubMed

    Rubenstein, E B; Escalante, C

    1989-07-01

    Hypertensive crisis is an acute emergency requiring aggressive management. Its incidence has decreased in recent years but still is prevalent in the medical community. From review of past and present treatment regimens, the following recommendations can be considered. (1) In the treatment of malignant hypertension with associated CHF, sodium nitroprusside is still an excellent agent. It has a rapid onset of action and blood pressure can be easily titrated. Nitroglycerin is also another agent that can be used in this situation. (2) In the treatment of malignant hypertension with associated aortic dissection, trimethophan camsylate is the preferred agent. An alternative choice is the combination of nitroprusside and labetalol. (3) In the treatment of malignant hypertension with associated myocardial ischemia, an excellent choice is nitroglycerin. Labetalol also should be considered in this situation. (4) In the treatment of hypertension during pregnancy, hydralazine is still a good choice. Labetalol has also been shown to be efficacious. (5) In the treatment of malignant hypertension with associated cerebral ischemia, the following drugs should be considered: nitroprusside, nitroglycerin, and labetalol. The most important attribute of these agents is that they are nonsedating and rapid in onset. (6) In the treatment of postoperative hypertension the choices best suited are labetalol, enalapril, nitroprusside, and nitroglycerin. These agents are rapid in onset and all can be administered intravenously. PMID:2670090

  2. Role of Nox4 and p67phox subunit of Nox2 in ROS production in response to increased tubular flow in the mTAL of Dahl salt-sensitive rats.

    PubMed

    Zheleznova, Nadezhda N; Yang, Chun; Cowley, Allen W

    2016-08-01

    Nox4 and Nox2 are the most abundant NADPH oxidases (Nox) in the kidney and have been shown to contribute to hypertension, renal oxidative stress, and injury in Dahl salt-sensitive (SS) hypertensive rats. The present study focused on the role of Nox4 and p67phox/Nox2 in the generation of H2O2 and O2 (·-) in the renal medullary thick ascending limb of Henle (mTAL) of SS rats in response to increasing luminal flow (from 5 to 20 nl/min). Nox4 and p67phox/Nox2 genes were found to be expressed in the mTAL of SS rats. Responses of SS rats were compared with those of SS rats with knockout of Nox4 (SS(Nox4-/-)) or functional mutation of p67phox (SS(p67phox-/-)). Nox4 was the dominant source of increased intracellular H2O2 production in response to increased luminal flow as determined using the fluorescent dye peroxyfluor 6-AM (PF6-AM). The rate of mitochondrial H2O2 production [as determined by mitochondria peroxy yellow 1 (mitoPY1)] was also significantly reduced in SS(Nox4-/-) compared with SS rats, but not in SS(p67phox-/-) rats. In contrast, intracellular superoxide (O2 (·-)) production (the ratio of ethidium to dihydroethidium) in the mTAL of SS(Nox4-/-) rats was nearly identical to that of SS rats in response to luminal flow, indicating that Nox4 made no measurable contribution. mTAL O2 (·-) production was reduced in SS(p67phox-/-) compared with SS rats at the lower luminal flow of 5 nl/min and progressively increased when perfusion was changed to 20 nl/min. We conclude that increased mTAL luminal flow results in increases in intracellular and mitochondrial H2O2, which are dependent on the presence of Nox4, and that p67phox/Nox2 accounts solely for increases in O2 (·-) production. PMID:27279484

  3. Optical cryoimaging of rat kidney and the effective role of chromosome 13 in salt-induced hypertension

    NASA Astrophysics Data System (ADS)

    Salehpour, F.; Yang, C.; Kurth, T.; Cowley, A. W.; Ranji, M.

    2015-03-01

    The objective of this work is to assess oxidative stress levels in salt-sensitive hypertension animal model using 3D optical cryoimager to image mitochondrial redox ratio. We studied Dahl salt-induced (SS) rats, and compared the results with a consomic SS rat strain (SSBN13). The SSBN13 strain was developed by the introgression of chromosome from the Brown Norway (BN) rat into the salt-sensitive (SS) genetic background and exhibits significant protection from salt induced hypertension1 . These two groups were fed on a high salt diet of 8.0% NaCl for one week. Mitochondrial redox ratio (NADH/FAD=NADH RR), was used as a quantitative marker of the oxidative stress in kidney tissue. Maximum intensity projected images and their corresponding histograms in each group were acquired from each kidney group. The result showed a 49% decrease in mitochondrial redox ratio of SS compared to SSBN13 translated to an increase in the level of oxidative stress of the tissue. Therefore, the results quantify oxidative stress levels and its effect on mitochondrial redox in salt sensitive hypertension.

  4. Psychobiology of experimental hypertension: evaluation of the Dahl rat lines

    SciTech Connect

    Haber, S.B.; Friedman, R.

    1981-01-01

    The Dahl salt-sensitive (DS) and salt-resistant (DR) rat lines were selectively bred to show opposite genetically determined blood pressure responses to excess sodium chloride ingestion. These animals have provided significant anatomical, physiological, and biochemical data concerning the pathological mechanisms of experimental hypertension. Research is also being conducted to determine the relevance of psychobiological and behavioral variables in these two lines. The rationale for the selection and maintenance of the Dahl model and the physiological, biochemical, and behavioral characteristics which distinguish DS and DR rats are presented. Although originally developed for the study of salt-induced hypertension, special attention is given to the application of this animal model in behavior genetic research, stressing its inherent advantages and limitations. The use of the Dahl model in psychobiological studies and the utility of the model for future behavioral, genetic, and psychophysiological research are also detailed.

  5. Pulmonary Hypertension

    MedlinePlus

    Pulmonary hypertension (PH) is high blood pressure in the arteries to your lungs. It is a serious condition. If you have ... and you can develop heart failure. Symptoms of PH include Shortness of breath during routine activity, such ...

  6. Hypertension screening

    NASA Technical Reports Server (NTRS)

    Foulke, J. M.

    1975-01-01

    An attempt was made to measure the response to an announcement of hypertension screening at the Goddard Space Center, to compare the results to those of previous statistics. Education and patient awareness of the problem were stressed.

  7. [Hypertensive retinopathy].

    PubMed

    Genevois, Olivier; Paques, Michel

    2010-01-20

    Acute hypertensive retinopathy should be distinguished from retinal arteriolosclerosis. The presence of microvascular abnormalities in the ocular fundus increases the risk of heart and/or brain attack. At the clinical level, the current classification of chronic hypertensive retinopathy is based on the long-term risk of stroke. In research, a great number of studies are focused on the predictive value of retinal vascular diameters related to the general micro- and macrovascular disease. PMID:20222306

  8. Overexpression of a tobacco small G protein gene NtRop1 causes salt sensitivity and hydrogen peroxide production in transgenic plants.

    PubMed

    Cao, YangRong; Li, ZhiGang; Chen, Tao; Zhang, ZhiGang; Zhang, JinSong; Chen, ShouYi

    2008-05-01

    The small GTPases of Rop/Rho family is central regulators of important cellular processes in plants. Tobacco small G protein gene NtRop1 has been isolated; however, its roles in stress responses were unknown. In the present study, the genomic sequence of NtRop1 was cloned, which has seven exons and six introns, similar to the Rop gene structure from Arabidopsis. The NtRop1 gene was constitutively expressed in the different organs whereas the other six Rop genes from tobacco had differential expression patterns. The expression of the NtRop1 gene was moderately induced by methyl viologen, NaCl, and ACC treatments, but slightly inhibited by ABA treatment, with no significant induction by NAA treatment. The transgenic Arabidopsis plants overexpressing the NtRop1 showed increased salt sensitivity as can be seen from the reduced root growth and elevated relative electrolyte leakage. The hydrogen peroxide production was also promoted in the NtRop1-trangenic plants in comparison with wild type plants. These results imply that the NtRop1 may confer salt sensitivity through activation of H2O2 production during plant response to salt stress. PMID:18785583

  9. Pulmonary Hypertension

    PubMed Central

    Newman, John H.

    2005-01-01

    The modern era in cardiopulmonary medicine began in the 1940s, when Cournand and Richards pioneered right-heart catheterization. Until that time, no direct measurement of central vascular pressure had been performed in humans. Right-heart catheterization ignited an explosion of insights into function and dysfunction of the pulmonary circulation, cardiac performance, ventilation–perfusion relationships, lung–heart interactions, valvular function, and congenital heart disease. It marked the beginnings of angiocardiography with its diagnostic implications for diseases of the left heart and peripheral circulation. Pulmonary hypertension was discovered to be the consequence of a large variety of diseases that either raised pressure downstream of the pulmonary capillaries, induced vasoconstriction, increased blood flow to the lung, or obstructed the pulmonary vessels, either by embolism or in situ fibrosis. Hypoxic vasoconstriction was found to be a major cause of acute and chronic pulmonary hypertension, and surprising vasoreactivity of the pulmonary vascular bed was discovered to be present in many cases of severe pulmonary hypertension, initially in mitral stenosis. Diseases as disparate as scleroderma, cystic fibrosis, kyphoscoliosis, sleep apnea, and sickle cell disease were found to have shared consequences in the pulmonary circulation. Some of the achievements of Cournand and Richards and their scientific descendents are discussed in this article, including success in the diagnosis and treatment of idiopathic pulmonary arterial hypertension, chronic thromboembolic pulmonary hypertension, and management of hypoxic pulmonary hypertension. PMID:15994464

  10. Systemic hypertension.

    PubMed

    Elliott, William J

    2007-04-01

    Hypertension is a growing public health problem worldwide. Only 37% of American hypertensives currently have their blood pressures controlled. Hypertension is traditionally diagnosed in the medical office, but both home and ambulatory blood pressure monitoring can help. Lifestyle modifications are recommended for everyone who has higher than "normal" blood pressure (<120/80 mm Hg). Voluminous clinical trial data support beginning drug therapy with low-dose chlorthalidone, unless the patient has a specific indication for a different drug. Additional drugs (typically in the sequence, angiotensin converting-enzyme inhibitor or angiotensin receptor blocker, calcium antagonist, beta-blocker, alpha-blocker, aldosterone antagonist, direct vasodilator, and centrally acting alpha(2)-agonist) can be added to achieve the blood pressure goal (usually <140/90 mm Hg, but <130/80 mm Hg for diabetics and those with chronic kidney disease). Special circumstances exist for treatment of hypertension in pregnancy, in childhood, in the elderly, and in both extremes of blood pressure (pre-hypertension or hypertensive emergencies). PMID:17398315

  11. Hypertensive emergencies.

    PubMed

    Murphy, C

    1995-11-01

    Hypertensive emergencies are uncommon and physiologically diverse. Consequently, it is difficult for most physicians to develop a familiarity with all the different hypertensive crises and with all drugs available for treating them (Table 4). Clinicians should not agonize over which is the perfect therapeutic agent for a particular emergency, but instead, they should focus on scrupulous monitoring and familiarize themselves with a few agents that will serve in most situations. Generally, these agents will be sodium nitroprusside and nitroglycerin. Vigilant neurologic monitoring is mandatory in all hypertensive emergencies. The early symptoms and signs of cerebral hypoperfusion can be vague and subtle, but if recognized, serious complications of therapy can be avoided. Remember, the patient may still be hypertensive. Avoid acute (during the first hour) reductions in MAP of more than 20% whenever possible; subsequent reductions should be gradual. In patients known to have markedly elevated ICP and who need acute reductions in their BP, serious consideration should be given to direct monitoring of the ICP so that CPP can be maintained within safe limits. In general, oral agents should not be used for the treatment of hypertensive emergencies. Intravenous Labetalol and intravenous nicardipine are not suitable for general use in hypertensive emergencies. In special situations (e.g., perioperative hypertension and subarachnoid hemorrhage), however, they may be employed. Their role may expand with further study. Trimethaphan may be superior to nitroprusside for hypertension complicated by elevated ICP or cerebral dysfunction. Realistically, most physicians will continue to use nitroprusside. Intense neurologic monitoring is more important than the specific agent used. Nitroglycerin is the agent of choice for acute ischemic heart disease complicated by severe hypertension; if it fails, use nitroprusside. For aortic dissection, the combination of nitroprusside and IV

  12. Pathogenesis of essential hypertension: historical paradigms and modern insights

    PubMed Central

    Johnson, Richard J.; Feig, Dan I.; Nakagawa, Takahiko; Sanchez-Lozada, L. Gabriela; Rodriguez-Iturbe, Bernardo

    2009-01-01

    Since its first identification in the late 1800s, a variety of etiologies for essential hypertension have been proposed. In this paper we review the primary proposed hypotheses in the context of both the time in which they were proposed as well as the subsequent studies performed over the years. From these various insights, we propose a current paradigm to explain the renal mechanisms underlying the hypertension epidemic today. Specifically, we propose that hypertension is initiated by agents that cause systemic and intrarenal vasoconstriction. Over time intrarenal injury develops with microvascular disease, interstitial T cell and macrophage recruitment with the induction of an autoimmune response, with local angiotensin II formation and oxidant generation. These changes maintain intrarenal vasoconstriction and hypoxia with a change in local vasoconstrictor-vasodilator balance favoring sodium retention. Both genetic and congenital (nephron number) mechanisms have profound influence on this pathway. As blood pressure rises, renal ischemia is ameliorated and sodium balance restored completely (in salt-resistant) or partially (in salt-sensitive) hypertension, but at the expense of a rightward shift in the pressure natriuresis curve and persistent hypertension. PMID:18300843

  13. Types of Pulmonary Hypertension

    MedlinePlus

    ... from the NHLBI on Twitter. Types of Pulmonary Hypertension The World Health Organization divides pulmonary hypertension (PH) ... are called pulmonary hypertension.) Group 1 Pulmonary Arterial Hypertension Group 1 PAH includes: PAH that has no ...

  14. Diagnosing hypertension

    PubMed Central

    Gelfer, Mark; Dawes, Martin; Kaczorowski, Janusz; Padwal, Raj; Cloutier, Lyne

    2015-01-01

    Abstract Objective To highlight the 2015 Canadian Hypertension Education Program (CHEP) recommendations for the diagnosis and assessment of hypertension. Quality of evidence A systematic search was performed current to August 2014 by a Cochrane Collaboration librarian using the MEDLINE and PubMed databases. The search results were critically appraised by the CHEP subcommittee on blood pressure (BP) measurement and diagnosis, and evidence-based recommendations were presented to the CHEP Central Review Committee for independent review and grading. Finally, the findings and recommendations were presented to the Recommendations Task Force for discussion, debate, approval, and voting. The main recommendations are based on level II evidence. Main message Based on the most recent evidence, CHEP has made 4 recommendations in 2 broad categories for 2015 to improve BP measurement and the way hypertension is diagnosed. A strong recommendation is made to use electronic BP measurement in the office setting to replace auscultatory BP measurement. For patients with elevated office readings, CHEP is recommending early use of out-of-office BP measurement, preferably ambulatory BP measurement, in order to identify early in the process those patients with white-coat hypertension. Conclusion Improvements in diagnostic accuracy are critical to optimizing hypertension management in Canada. The annual updates provided by CHEP ensure that practitioners have up-to-date evidence-based information to inform practice. PMID:26564654

  15. [Portopulmonary hypertension].

    PubMed

    Halank, M; Miehlke, S; Kolditz, M; Hoeffken, G

    2005-07-01

    Patients with portal hypertension may develop pulmonary complications such as hepatopulmonary syndrome (HPS) or portopulmonary hypertension (PPHT). PPHT is defined as elevated pulmonary pressure, elevated pulmonary vascular resistance, a normal pulmonary capillary wedge pressure, and portal hypertension in the absence of other known causes pulmonary hypertension. Various factors such as hyperdynamic circulation, volume overload, and circulating vasoactive mediators are suspected to be involved in the pathogenesis of PPHT. The prognosis of patients with severe PPHT is significantly reduced due to the risk of right heart failure. In patients with moderate to severe PPHT liver transplantation is associated with a significantly increased mortality. The chief symptom of PPHT may be dyspnoe in the presence of typical histomorphological alterations comparable with idiopathic pulmonary hypertension. Continuous intravenous application of prostacyclin is currently regarded as the treatment of choice for patients with severe PPHT. Inhaled prostacyclin or its analogue iloprost or oral treatment with the endothelin-receptor antagonist bosentan may be promising alternatives which should be further investigated in randomized controlled trials. PMID:16001350

  16. Transcriptome analysis reveals that distinct metabolic pathways operate in salt-tolerant and salt-sensitive upland cotton varieties subjected to salinity stress.

    PubMed

    Guo, Jinyan; Shi, Gongyao; Guo, Xiaoyan; Zhang, Liwei; Xu, Wenying; Wang, Yumei; Su, Zhen; Hua, Jinping

    2015-09-01

    Salinity stress is one of the most devastating abiotic stresses in crop plants. As a moderately salt-tolerant crop, upland cotton (Gossypium hirsutum L.) is a major cash crop in saline areas and a suitable model for salt stress tolerance research. In this study, we compared the transcriptome changes between the salt-tolerant upland cotton cultivar Zhong 07 and salt-sensitive cultivar Zhong G5 in response to NaCl treatments. Transcriptional regulation, signal transduction and secondary metabolism in two varieties showed significant differences, all of which might be related to mechanisms underlying salt stress tolerance. The transcriptional profiles presented here provide a foundation for deciphering the mechanism underlying salt tolerance. Based on our findings, we proposed several candidate genes that might be used to improve salt tolerance in upland cotton. PMID:26259172

  17. Resveratrol affects histone 3 lysine 27 methylation of vessels and blood biomarkers in DOCA salt-induced hypertension.

    PubMed

    Han, Sevtap; Uludag, Mecit Orhan; Usanmaz, Suzan Emel; Ayaloglu-Butun, Fatma; Akcali, Kamil Can; Demirel-Yilmaz, Emine

    2015-01-01

    Hypertension is a risk factor for the cardiovascular diseases. Although, several drugs are used to treat hypertension, the success of the antihypertensive therapy is limited. Resveratrol decreases blood pressure in animal models of hypertension. This study researched the mechanisms behind the effects of resveratrol on hypertension. Hypertension was induced by using the deoxycorticosterone acetate (DOCA)-induced (15 mg/kg twice per week, subcutaneously) salt-sensitive hypertension model of Wistar rats. Hypertension caused a decrease in endothelium-dependent relaxations of the isolated thoracic aorta. Resveratrol treatment (50 mg/l in drinking water) prevented DOCA salt-induced hypertension, but did not improve endothelial dysfunction. Plasma nitric oxide (NO), asymmetric dimethylarginine (ADMA), total antioxidant capacity (TAC) and hydrogen sulfide (H2S) levels were not changed by DOCA salt application. However, treatment of resveratrol significantly decreased ADMA and increased TAC and H2S levels. NO level in circulation was not significantly changed by resveratrol. DOCA salt application and resveratrol treatment also caused an alteration in the epigenetic modification of vessels. Staining pattern of histone 3 lysine 27 methylation (H3K27me3) in the aorta and renal artery sections was changed. These results show that preventive effect of resveratrol on DOCA salt-induced hypertension might due to its action on the production of some blood biomarkers and the epigenetic modification of vessels that would focus upon new aspect of hypertension prevention and treatment. PMID:25234650

  18. Pathway analysis of the transcriptome and metabolome of salt sensitive and tolerant poplar species reveals evolutionary adaption of stress tolerance mechanisms

    PubMed Central

    2010-01-01

    Background Populus euphratica is a salt tolerant and Populus × canescens a salt sensitive poplar species. Because of low transcriptional responsiveness of P. euphratica to salinity we hypothesized that this species exhibits an innate activation of stress protective genes compared with salt sensitive poplars. To test this hypothesis, the transcriptome and metabolome of mature unstressed leaves of P. euphratica and P. × canescens were compared by whole genome microarray analyses and FT-ICR-MS metabolite profiling. Results Direct cross-species comparison of the transcriptomes of the two poplar species from phylogenetically different sections required filtering of the data set. Genes assigned to the GO slim categories 'mitochondria', 'cell wall', 'transport', 'energy metabolism' and 'secondary metabolism' were significantly enriched, whereas genes in the categories 'nucleus', 'RNA or DNA binding', 'kinase activity' and 'transcription factor activity' were significantly depleted in P. euphratica compared with P. × canescens. Evidence for a general activation of stress relevant genes in P. euphratica was not detected. Pathway analyses of metabolome and transcriptome data indicated stronger accumulation of primary sugars, activation of pathways for sugar alcohol production, and faster consumption of secondary metabolites in P. euphratica compared to P. × canescens. Physiological measurements showing higher respiration, higher tannin and soluble phenolic contents as well as enrichment of glucose and fructose in P. euphratica compared to P. × canescens corroborated the results of pathway analyses. Conclusion P. euphratica does not rely on general over-expression of stress pathways to tolerate salt stress. Instead, it exhibits permanent activation of control mechanisms for osmotic adjustment (sugar and sugar alcohols), ion compartmentalization (sodium, potassium and other metabolite transporters) and detoxification of reactive oxygen species (phenolic compounds). The

  19. Pulmonary Hypertension

    MedlinePlus

    Pulmonary hypertension (PH) is high blood pressure in the arteries to your lungs. It is a serious condition. If you have it, the blood ... heart has to work harder to pump the blood through. Over time, your heart weakens and ... of PH include Shortness of breath during routine activity, such ...

  20. Portopulmonary hypertension.

    PubMed

    Lv, Yong; Han, Guohong; Fan, Daiming

    2016-07-01

    Portopulmonary hypertension (PoPH) refers to the condition that pulmonary arterial hypertension (PAH) occur in the stetting of portal hypertension. The development of PoPH is thought to be independent of the severity of portal hypertension or the etiology or severity of liver disease. PoPH results from excessive vasoconstriction, vascular remodeling, and proliferative and thrombotic events within the pulmonary circulation that lead to progressive right ventricular failure and ultimately to death. Untreated PoPH is associated with a poor prognosis. As PoPH is frequently asymptomatic or symptoms are generally non-specific, patients should be actively screened for the presence of PoPH. Two-dimensional transthoracic echocardiography is a useful non-invasive screening tool, but a definitive diagnosis requires invasive hemodynamic confirmation by right heart catheterization. Despite a dearth of randomized, prospective data, an ever-expanding clinical experience shows that patients with PoPH benefit from therapy with PAH-specific medications including with endothelin receptor antagonists, phosphodiesterase-5 inhibitors, and/or prostanoids. Due to high perioperative mortality, transplantation should be avoided in those patients who have severe PoPH that is refractory to medical therapy. PMID:27002212

  1. Pulmonary Hypertension

    MedlinePlus

    ... Anticoagulants (blood-thinning medicine) Calcium channel blockers Diuretics (water pills) Digoxin Your doctor will decide what type of medicine is right for you. In some cases, people who have pulmonary hypertension need surgical treatment. Surgical treatment options include a lung transplant and ...

  2. Hypertensive leucocytosis.

    PubMed

    Rajkumari, Rolinda; Laishram, Deben; Thiyam, Joshna; Javan, Ng

    2013-04-01

    There are studies showing association of high WBC count with the higher incidence of hypertension though a few are done in the Indian population. The present study was conducted with the view to find any significant increase in total leucocyte count and differential leucocyte count in hypertensive patient Twenty-seven hypertensives with 12 males and 15 females and 27 age and sex matched control subjects (normotensive) were studied. Hypertension was defined when the systolic BP > or = 140 mmHg or diastolic BP > or = 90 mmHg or history of taking antihypertensive medicine. Three blood pressure recordings at an interval of 2 minutes were taken after the patient was made to sit for 30 minutes with a standard mercury sphygmomanometer in the left arm. The disappearance of sound was used for diastolic blood pressure. Blood was drawn into EDTA containing vials. Two separate counts were performed: First for total leucocyte count (TLC) and second for determination of percentage of polymorphonuclear cells. For the TLC, 0.5 part of blood mixed with 10 part of Turk's fluid followed by counting of leucocyte in a counting chamber under light microscope. The percentage of polymorphonuclear leucocyte was performed on a slide after making the slide and staining it with Leishman's stain. The erythrocyte sedimentation rate (ESR) was performed using Wintrobe's methods. The first 1 hour reading on the Wintrobe's tube was taken for analysis. The total leucocyte count (TLC) for the study group as compared to the controls were 7413.70 +/- 735.45 cells/cmm and 5236.30 +/- 528.77 cells/ cmm which was statistically significant. The mean percentage neutrophils were 62.04 +/- 4.99 for study group and 53.00 +/- 3.44 for the controls; the mean percentage lymphocytes for the study group and the controls were 34.37 +/- 4.55 and 39.11 +/- 4.40 respectively. Both the mean percentage neutrophils and lymphocytes showed significant differences. The mean erythrocyte sedimentation rate (ESR) also showed

  3. Hypertension: salt restriction, sodium homeostasis, and other ions.

    PubMed

    Gupta, Neeru; Jani, Kishan Kumar; Gupta, Nivedita

    2011-03-01

    Salt is composed of Sodium Chloride (NaCl) which in body water becomes essential electrolytes, viz., Sodium (Na⁺) and Chloride (Cl⁻) ions, including in the blood and other extracellular fluids (ECF). Na⁺ ions are necessary cations in muscle contractions and their depletion will effect all the muscles in body including smooth muscle contraction of blood vessels, a fact which is utilized in lowering the blood pressure. Na⁺ ions also hold water with them in the ECF. Na⁺ homeostasis in body is maintained by thirst (water intake), kidneys (urinary excretion) and skin (sweating). In Na⁺ withdrawal, body tries to maintain homeostasis as far as possible. However, in certain conditions (e.g., during exercise, intake of drugs and in disorders causing Syndrome of Inappropriate Anti Diuretic Hormone Secretion (SIADH), diuretics, diarrhea) coupled with moderate or severe dietary salt restriction (anorexia nervosa), hyponatremia can get precipitated. Hyponatremia is one end point in the spectrum of disorders caused by severe Na⁺ depletion whereas in moderate depletion it can cause hypohydration (or less total body water) and lower urinary volume (U v ). Moreover, salt sensitivity varies in various populations leading to different responses in relation to dietary Na⁺ intake. Diabetes and Hypertension often co-exist but Na⁺ withdrawal in salt sensitive subjects worsens diabetes though hypertension gets better and reverse occurs in salt loading. Therefore, Na⁺ or salt restriction may be non-physiological. In hypertensive subjects other alternatives to Na⁺ withdrawal could be Potassium (K⁺) and Calcium (Ca⁺²) supplementation. Further studies are required to monitor safety/side effects of salt restriction. PMID:23250294

  4. Hypertension Subtypes among Hypertensive Patients in Ibadan

    PubMed Central

    Salako, Babatunde L.; Ogunniyi, Adesola; Cooper, Richard S.

    2014-01-01

    Background. Certain hypertension subtypes have been shown to increase the risk for cardiovascular morbidity and mortality and may be related to specific underlying genetic determinants. Inappropriate characterization of subtypes of hypertension makes efforts at elucidating the genetic contributions to the etiology of hypertension largely vapid. We report the hypertension subtypes among patients with hypertension from South-Western Nigeria. Methods. A total of 1858 subjects comprising 76% female, hypertensive, aged 18 and above were recruited into the study from two centers in Ibadan, Nigeria. Hypertension was identified using JNCVII definition and was further grouped into four subtypes: controlled hypertension (CH), isolated systolic hypertension (ISH), isolated diastolic hypertension (IDH), and systolic-diastolic hypertension (SDH). Results. Systolic-diastolic hypertension was the most prevalent. Whereas SDH (77.6% versus 73.5%) and IDH (4.9% versus 4.7%) were more prevalent among females, ISH (10.1% versus 6.2%) was higher among males (P = 0.048). Female subjects were more obese (P < 0.0001) and SDH was prevalent among the obese group. Conclusion. Gender and obesity significantly influenced the distribution of the hypertension subtypes. Characterization of hypertension by subtypes in genetic association studies could lead to identification of previously unknown genetic variants involved in the etiology of hypertension. Large-scale studies among various ethnic groups may be needed to confirm these observations. PMID:25389499

  5. Comparative expression analysis of Calcineurin B-like family gene CBL10A between salt-tolerant and salt-sensitive cultivars in B. oleracea.

    PubMed

    Xu, Ling; Zhang, Dayong; Xu, Zhaolong; Huang, Yihong; He, Xiaolan; Wang, Jinyan; Gu, Minfeng; Li, Jianbin; Shao, Hongbo

    2016-11-15

    Calcineurin B-like proteins (CBLs) are plant calcium sensors that play a critical role in the regulation of plant growth and response to stress. Many CBLs have been identified in the calcium signaling pathway in both Arabidopsis and rice. However, information about BoCBLs genes from Brassica oleracea has not been reported. In the present study, we identified 13 candidate CBL genes in the B. oleracea genome based on the conserved domain of the Calcineurin B-like family, and we carried out a phylogenetic analysis of CBLs among Arabidopsis, rice, maize, cabbage and B. oleracea. For B. oleracea, the distribution of the predicted BoCBL genes was uneven among the five chromosomes. Sequence analysis showed that the nucleotide sequences and corresponding protein structure of BoCBLs were highly conserved, i.e., all of the putative BoCBLs contained 6-8 introns, and most of the exons of those genes contained the same number of nucleotides and had high sequence identities. All BoCBLs consisted of four EF-Hand functional domains, and the distance between the EF-hand motifs was conserved. Evolutionary analysis revealed that the CBLs were classified into two subgroups. Additionally, the CBL10A gene was cloned from salt-tolerant (CB6) and salt-sensitive (CB3) cultivars using RT-PCR. The results indicated that the cloned gene had a substantial difference in length (741bp in CB3 and 829bp in CB6) between these two cultivars. The deduced CBL10A protein in CB6 had four EF-hand structural domains, which have an irreplaceable role in calcium-binding and have calcineurin A subunit binding sites, while the BoCBL10A protein in CB3 had only two EF-hand structural domains and lacked calcineurin A subunit binding sites. The expression level of the BoCBL10A gene between salt tolerance (CB6)and sensitive varieties(CB3) under salt stress was significantly different (P<0.01 and P<0.05). The expression of BoCBL10A gene was relatively higher in salt-tolerant (CB6) cultivar under salt stress, with a

  6. Pulmonary Arterial Hypertension

    MedlinePlus

    ... What Is Pulmonary Hypertension? To understand pulmonary hypertension (PH) it helps to understand how blood ows throughout ... is too high, it is called pulmonary hypertension (PH). How the pressure in the right side of ...

  7. Hypertension and Spina Bifida

    MedlinePlus

    SBA National Resource Center: 800-621-3141 Hypertension A disease that often goes undetected. What is hypertension? Hypertension, also called high blood pressure , is a condition in which the arteries of ...

  8. What Causes Pulmonary Hypertension?

    MedlinePlus

    ... from the NHLBI on Twitter. What Causes Pulmonary Hypertension? Pulmonary hypertension (PH) begins with inflammation and changes in the ... different types of PH. Group 1 pulmonary arterial hypertension (PAH) may have no known cause, or the ...

  9. Hormones and Hypertension

    MedlinePlus

    Fact Sheet Hormones and Hypertension What is hypertension? Hypertension, or chronic (long-term) high blood pressure, is a main cause of ... tobacco, alcohol, and certain medications play a part. Hormones made in the kidneys and in blood vessels ...

  10. African Americans, hypertension and the renin angiotensin system

    PubMed Central

    Williams, Sandra F; Nicholas, Susanne B; Vaziri, Nosratola D; Norris, Keith C

    2014-01-01

    African Americans have exceptionally high rates of hypertension and hypertension related complications. It is commonly reported that the blood pressure lowering efficacy of renin angiotensin system (RAS) inhibitors is attenuated in African Americans due to a greater likelihood of having a low renin profile. Therefore these agents are often not recommended as initial therapy in African Americans with hypertension. However, the high prevalence of comorbid conditions, such as diabetes, cardiovascular and chronic kidney disease makes treatment with RAS inhibitors more compelling. Despite lower circulating renin levels and a less significant fall in blood pressure in response to RAS inhibitors in African Americans, numerous clinical trials support the efficacy of RAS inhibitors to improve clinical outcomes in this population, especially in those with hypertension and risk factors for cardiovascular and related diseases. Here, we discuss the rationale of RAS blockade as part of a comprehensive approach to attenuate the high rates of premature morbidity and mortality associated with hypertension among African Americans. PMID:25276290

  11. Synthesis and Properties of pH-, Thermo-, and Salt-Sensitive Modified Poly(aspartic acid)/Poly(vinyl alcohol) IPN Hydrogel and Its Drug Controlled Release.

    PubMed

    Lu, Jingqiong; Li, Yinhui; Hu, Deng; Chen, Xiaoling; Liu, Yongmei; Wang, Liping; Zhao, Yansheng

    2015-01-01

    Modified poly(aspartic acid)/poly(vinyl alcohol) interpenetrating polymer network (KPAsp/PVA IPN) hydrogel for drug controlled release was synthesized by a simple one-step method in aqueous system using poly(aspartic acid) grafting 3-aminopropyltriethoxysilane (KH-550) and poly(vinyl alcohol) (PVA) as materials. The hydrogel surface morphology and composition were characterized by Fourier transform infrared spectroscopy (FTIR) and scanning electron microscopy (SEM). The thermal stability was analyzed by thermogravimetric analysis (TGA). The swelling properties and pH, temperature, and salt sensitivities of KPAsp, KPAsp/PVA semi-interpenetrating polymer network (semi-IPN), and KPAsp/PVA IPN hydrogels were also investigated. All of the three hydrogels showed ampholytic pH-responsive properties, and swelling behavior was also extremely sensitive to the temperature, ionic strength, and cationic species. Finally, the drug controlled release properties of the three hydrogels were evaluated and results indicated that three hydrogels could control drug release by external surroundings stimuli. The drug controlled release properties of KPAsp/PVA IPN hydrogel are the most outstanding, and the correlative measured release profiles of salicylic acid at 37°C were 32.6 wt% at pH = 1.2 (simulated gastric fluid) and 62.5 wt% at pH = 7.4 (simulated intestinal fluid), respectively. These results indicated that KPAsp/PVA IPN hydrogels are a promising carrier system for controlled drug delivery. PMID:26351630

  12. Molecular and physiological responses to abscisic acid and salts in roots of salt-sensitive and salt-tolerant Indica rice varieties.

    PubMed Central

    Moons, A; Bauw, G; Prinsen, E; Van Montagu, M; Van der Straeten, D

    1995-01-01

    The Indica rice (Oryza sativa L.) varieties Pokkali and Nona Bokra are well-known salt tolerance donors in classical breeding. In an attempt to understand the molecular basis of their tolerance, physiological and gene expression studies were initiated. The effect of abscisic acid (ABA) on total proteins in roots from 12-d-old seedlings of Pokkali, Nona Bokra, and the salt-sensitive cultivar Taichung N1 were analyzed on two-dimensional gels. The abundance of ABA-induced proteins was highest in the most tolerant variety, Pokkali. Three ABA-responsive proteins, present at different levels in roots from tolerant and sensitive varieties, were further characterized by partial amino acid analysis. A novel histidine-rich protein and two types of late embryogenesis abundant (LEA) proteins were identified. Protein immunoblotting revealed that the levels of dehydrins and group 3 LEA proteins were significantly higher in roots from tolerant compared with sensitive varieties. Endogenous ABA levels showed a transient increase in roots exposed to osmotic shock (150 mM NaCl). Peak ABA concentrations were 30-fold higher for Nona Bokra and 6-fold higher for Pokkali compared with Taichung N1. Both the salt-induced endogenous ABA levels and a greater molecular response of root tissue to ABA were associated with the varietal differences in tolerance. PMID:7870812

  13. Synthesis and Properties of pH-, Thermo-, and Salt-Sensitive Modified Poly(aspartic acid)/Poly(vinyl alcohol) IPN Hydrogel and Its Drug Controlled Release

    PubMed Central

    Lu, Jingqiong; Li, Yinhui; Hu, Deng; Chen, Xiaoling; Liu, Yongmei; Wang, Liping; Zhao, Yansheng

    2015-01-01

    Modified poly(aspartic acid)/poly(vinyl alcohol) interpenetrating polymer network (KPAsp/PVA IPN) hydrogel for drug controlled release was synthesized by a simple one-step method in aqueous system using poly(aspartic acid) grafting 3-aminopropyltriethoxysilane (KH-550) and poly(vinyl alcohol) (PVA) as materials. The hydrogel surface morphology and composition were characterized by Fourier transform infrared spectroscopy (FTIR) and scanning electron microscopy (SEM). The thermal stability was analyzed by thermogravimetric analysis (TGA). The swelling properties and pH, temperature, and salt sensitivities of KPAsp, KPAsp/PVA semi-interpenetrating polymer network (semi-IPN), and KPAsp/PVA IPN hydrogels were also investigated. All of the three hydrogels showed ampholytic pH-responsive properties, and swelling behavior was also extremely sensitive to the temperature, ionic strength, and cationic species. Finally, the drug controlled release properties of the three hydrogels were evaluated and results indicated that three hydrogels could control drug release by external surroundings stimuli. The drug controlled release properties of KPAsp/PVA IPN hydrogel are the most outstanding, and the correlative measured release profiles of salicylic acid at 37°C were 32.6 wt% at pH = 1.2 (simulated gastric fluid) and 62.5 wt% at pH = 7.4 (simulated intestinal fluid), respectively. These results indicated that KPAsp/PVA IPN hydrogels are a promising carrier system for controlled drug delivery. PMID:26351630

  14. Conditional Deletion of Hsd11b2 in the Brain Causes Salt Appetite and Hypertension

    PubMed Central

    Evans, Louise C.; Ivy, Jessica R.; Wyrwoll, Caitlin; McNairn, Julie A.; Menzies, Robert I.; Christensen, Thorbjørn H.; Al-Dujaili, Emad A.S.; Kenyon, Christopher J.; Mullins, John J.; Seckl, Jonathan R.; Holmes, Megan C.

    2016-01-01

    Background— The hypertensive syndrome of Apparent Mineralocorticoid Excess is caused by loss-of-function mutations in the gene encoding 11β-hydroxysteroid dehydrogenase type 2 (11βHSD2), allowing inappropriate activation of the mineralocorticoid receptor by endogenous glucocorticoid. Hypertension is attributed to sodium retention in the distal nephron, but 11βHSD2 is also expressed in the brain. However, the central contribution to Apparent Mineralocorticoid Excess and other hypertensive states is often overlooked and is unresolved. We therefore used a Cre-Lox strategy to generate 11βHSD2 brain-specific knockout (Hsd11b2.BKO) mice, measuring blood pressure and salt appetite in adults. Methods and Results— Basal blood pressure, electrolytes, and circulating corticosteroids were unaffected in Hsd11b2.BKO mice. When offered saline to drink, Hsd11b2.BKO mice consumed 3 times more sodium than controls and became hypertensive. Salt appetite was inhibited by spironolactone. Control mice fed the same daily sodium intake remained normotensive, showing the intrinsic salt resistance of the background strain. Dexamethasone suppressed endogenous glucocorticoid and abolished the salt-induced blood pressure differential between genotypes. Salt sensitivity in Hsd11b2.BKO mice was not caused by impaired renal sodium excretion or volume expansion; pressor responses to phenylephrine were enhanced and baroreflexes impaired in these animals. Conclusions— Reduced 11βHSD2 activity in the brain does not intrinsically cause hypertension, but it promotes a hunger for salt and a transition from salt resistance to salt sensitivity. Our data suggest that 11βHSD2-positive neurons integrate salt appetite and the blood pressure response to dietary sodium through a mineralocorticoid receptor–dependent pathway. Therefore, central mineralocorticoid receptor antagonism could increase compliance to low-sodium regimens and help blood pressure management in cardiovascular disease. PMID

  15. Essential Hypertension vs. Secondary Hypertension Among Children

    PubMed Central

    Banker, Ashish; Shete, Sanjay; Hashmi, Syed Sharukh; Tyson, John E.; Barratt, Michelle S.; Hecht, Jacqueline T.; Milewicz, Diane M.; Boerwinkle, Eric

    2015-01-01

    BACKGROUND The aim was to determine the proportions and correlates of essential hypertension among children in a tertiary pediatric hypertension clinic. METHODS We evaluated 423 consecutive children and collected demographic and clinical history by retrospective chart review. RESULTS We identified 275 (65%) hypertensive children (blood pressure >95th percentile per the “Fourth Report on the Diagnosis, Evaluation, and Treatment of High Blood Pressure in Children and Adolescents”) from 423 children referred to the clinic for history of elevated blood pressure. The remainder of the patients had normotension (11%), white coat hypertension (11%), prehypertension (10%), and pending diagnosis (3%). Among the 275 hypertensive children, 43% (n = 119; boys = 56%; median age = 12 years; range = 3–17 years) had essential hypertension and 57% (n = 156; boys = 66%; median age = 9 years; range = 0.08–19 years) had secondary hypertension. When compared with those with secondary hypertension, those with essential hypertension had a significantly older age at diagnosis (P = 0.0002), stronger family history of hypertension (94% vs. 68%; P < 0.0001), and lower prevalence of preterm birth (20% vs. 46%; P < 0.001). There was a bimodal distribution of age of diagnosis in those with secondary hypertension. CONCLUSIONS The phenotype of essential hypertension can present as early as 3 years of age and is the predominant form of hypertension in children after age of 6 years. Among children with hypertension, those with essential hypertension present at an older age, have a stronger family history of hypertension, and have lower prevalence of preterm birth. PMID:24842390

  16. [Hypertensive emergencies and urgencies].

    PubMed

    Reingardiene, Dagmara

    2005-01-01

    Hypertension is one of the most common medical problems affecting approximately 1 billion individuals worldwide. Severe hypertension that is a potentially life-threatening condition refers to a hypertensive crisis. Severe hypertension is further classified into hypertensive emergencies or hypertensive urgencies. Hypertensive emergency refers to a severe hypertension that is associated with new or progressive end-organ damage. In these clinical situations, blood pressure should be reduced immediately to prevent or minimize organ dysfunction. Hypertensive urgency refers to severe hypertension without evidence of new or worsening end-organ injury. Blood pressure can be lowered less rapidly in this condition. In this review article it is discussed about clinical assessment of patients under these conditions, evaluating neurological, cardiovascular, renal end-organ damage; how much blood pressure should be lowered, which medication should be used to lower blood pressure, treating hypertensive emergencies and urgencies; and management of specific conditions (acute intracranial events, acute left ventricular dysfunction etc). PMID:15998994

  17. GUT MICROBIOTA DYSBIOSIS IS LINKED TO HYPERTENSION

    PubMed Central

    Yang, Tao; Santisteban, Monica M.; Rodriguez, Vermali; Li, Eric; Ahmari, Niousha; Carvajal, Jessica Marulanda; Zadeh, Mojgan; Gong, Minghao; Qi, Yanfei; Zubcevic, Jasenka; Sahay, Bikash; Pepine, Carl J.; Raizada, Mohan K.; Mohamadzadeh, Mansour

    2015-01-01

    Emerging evidence suggests that gut microbiota is critical in the maintenance of physiological homeostasis. The present study was designed to test the hypothesis that dysbiosis in gut microbiota is associated with hypertension since genetic, environmental, and dietary factors profoundly influence both gut microbiota and blood pressure. Bacterial DNA from fecal samples of two rat models of hypertension and a small cohort of patients was used for bacterial genomic analysis. We observed a significant decrease in microbial richness, diversity, and evenness in the spontaneously hypertensive rat, in addition to an increased Firmicutes to Bacteroidetes ratio. These changes were accompanied with decreases in acetate- and butyrate-producing bacteria. Additionally, the microbiota of a small cohort of human hypertension patients was found to follow a similar dysbiotic pattern, as it was less rich and diverse than that of control subjects. Similar changes in gut microbiota were observed in the chronic angiotensin II infusion rat model, most notably decreased microbial richness and an increased Firmicutes to Bacteroidetes ratio. In this model, we evaluated the efficacy of oral minocycline in restoring gut microbiota. In addition to attenuating high blood pressure, minocycline was able to rebalance the dysbiotic hypertension gut microbiota by reducing the Firmicutes to Bacteroidetes ratio. These observations demonstrate that high BP is associated with gut microbiota dysbiosis, both in animal and human hypertension. They suggest that dietary intervention to correct gut microbiota could be an innovative nutritional therapeutic strategy for hypertension. PMID:25870193

  18. Gut dysbiosis is linked to hypertension.

    PubMed

    Yang, Tao; Santisteban, Monica M; Rodriguez, Vermali; Li, Eric; Ahmari, Niousha; Carvajal, Jessica Marulanda; Zadeh, Mojgan; Gong, Minghao; Qi, Yanfei; Zubcevic, Jasenka; Sahay, Bikash; Pepine, Carl J; Raizada, Mohan K; Mohamadzadeh, Mansour

    2015-06-01

    Emerging evidence suggests that gut microbiota is critical in the maintenance of physiological homeostasis. This study was designed to test the hypothesis that dysbiosis in gut microbiota is associated with hypertension because genetic, environmental, and dietary factors profoundly influence both gut microbiota and blood pressure. Bacterial DNA from fecal samples of 2 rat models of hypertension and a small cohort of patients was used for bacterial genomic analysis. We observed a significant decrease in microbial richness, diversity, and evenness in the spontaneously hypertensive rat, in addition to an increased Firmicutes/Bacteroidetes ratio. These changes were accompanied by decreases in acetate- and butyrate-producing bacteria. In addition, the microbiota of a small cohort of human hypertensive patients was found to follow a similar dysbiotic pattern, as it was less rich and diverse than that of control subjects. Similar changes in gut microbiota were observed in the chronic angiotensin II infusion rat model, most notably decreased microbial richness and an increased Firmicutes/Bacteroidetes ratio. In this model, we evaluated the efficacy of oral minocycline in restoring gut microbiota. In addition to attenuating high blood pressure, minocycline was able to rebalance the dysbiotic hypertension gut microbiota by reducing the Firmicutes/Bacteroidetes ratio. These observations demonstrate that high blood pressure is associated with gut microbiota dysbiosis, both in animal and human hypertension. They suggest that dietary intervention to correct gut microbiota could be an innovative nutritional therapeutic strategy for hypertension. PMID:25870193

  19. Hypertensive Emergencies in Pregnancy.

    PubMed

    Olson-Chen, Courtney; Seligman, Neil S

    2016-01-01

    The prevalence of hypertensive disorders in pregnancy is increasing. The etiology and pathophysiology of hypertensive disorders in pregnancy remain poorly understood. Hypertensive disorders are a major cause of maternal and perinatal morbidity and mortality. Treatment of hypertension decreases the incidence of severe hypertension, but it does not impact rates of preeclampsia or other pregnancy complications. Several antihypertensive medications are commonly used in pregnancy, although there is a lack of randomized controlled trials. Severe hypertension should be treated immediately to prevent maternal end-organ damage. Appropriate antepartum, intrapartum, and postpartum management is important in caring for patients with hypertensive disorders. PMID:26600442

  20. High dietary sodium reduces brachial artery flow-mediated dilation in humans with salt-sensitive and salt-resistant blood pressure.

    PubMed

    Matthews, Evan L; Brian, Michael S; Ramick, Meghan G; Lennon-Edwards, Shannon; Edwards, David G; Farquhar, William B

    2015-06-15

    Recent studies demonstrate that high dietary sodium (HS) impairs endothelial function in those with salt-resistant (SR) blood pressure (BP). The effect of HS on endothelial function in those with salt-sensitive (SS) BP is not currently known. We hypothesized that HS would impair brachial artery flow-mediated dilation (FMD) to a greater extent in SS compared with SR adults. Ten SR (age 42 ± 5 yr, 5 men, 5 women) and 10 SS (age 39 ± 5 yr, 5 men, 5 women) healthy, normotensive participants were enrolled in a controlled feeding study consisting of a run-in diet followed by a 7-day low dietary sodium (LS) (20 mmol/day) and a 7-day HS (300 mmol/day) diet in random order. Brachial artery FMD and 24-h BP were assessed on the last day of each diet. SS BP was individually assessed and defined as a change in 24-h mean arterial pressure (MAP) of >5 mmHg between the LS and HS diets (ΔMAP: SR -0.6 ± 1.2, SS 7.7 ± 0.4 mmHg). Brachial artery FMD was lower in both SS and SR individuals during the HS diet (P < 0.001), and did not differ between groups (P > 0.05) (FMD: SR LS 10.6 ± 1.3%, SR HS 7.2 ± 1.5%, SS LS 12.5 ± 1.7%, SS HS 7.8 ± 1.4%). These data indicate that an HS diet impairs brachial artery FMD to a similar extent in adults with SS BP and SR BP. PMID:26078434

  1. NaCl-Induced Alternations of Cellular and Tissue Ion Fluxes in Roots of Salt-Resistant and Salt-Sensitive Poplar Species1[C][W][OA

    PubMed Central

    Sun, Jian; Chen, Shaoliang; Dai, Songxiang; Wang, Ruigang; Li, Niya; Shen, Xin; Zhou, Xiaoyang; Lu, Cunfu; Zheng, Xiaojiang; Hu, Zanmin; Zhang, Zengkai; Song, Jin; Xu, Yue

    2009-01-01

    Using the scanning ion-selective electrode technique, fluxes of H+, Na+, and Cl− were investigated in roots and derived protoplasts of salt-tolerant Populus euphratica and salt-sensitive Populus popularis 35-44 (P. popularis). Compared to P. popularis, P. euphratica roots exhibited a higher capacity to extrude Na+ after a short-term exposure to 50 mm NaCl (24 h) and a long term in a saline environment of 100 mm NaCl (15 d). Root protoplasts, isolated from the long-term-stressed P. euphratica roots, had an enhanced Na+ efflux and a correspondingly increased H+ influx, especially at an acidic pH of 5.5. However, the NaCl-induced Na+/H+ exchange in root tissues and cells was inhibited by amiloride (a Na+/H+ antiporter inhibitor) or sodium orthovanadate (a plasma membrane H+-ATPase inhibitor). These results indicate that the Na+ extrusion in stressed P. euphratica roots is the result of an active Na+/H+ antiport across the plasma membrane. In comparison, the Na+/H+ antiport system in salt-stressed P. popularis roots was insufficient to exclude Na+ at both the tissue and cellular levels. Moreover, salt-treated P. euphratica roots retained a higher capacity for Cl− exclusion than P. popularis, especially during a long term in high salinity. The pattern of NaCl-induced fluxes of H+, Na+, and Cl− differs from that caused by isomotic mannitol in P. euphratica roots, suggesting that NaCl-induced alternations of root ion fluxes are mainly the result of ion-specific effects. PMID:19028881

  2. Mitochondrial Cyclophilin D in Vascular Oxidative Stress and Hypertension.

    PubMed

    Itani, Hana A; Dikalova, Anna E; McMaster, William G; Nazarewicz, Rafal R; Bikineyeva, Alfiya T; Harrison, David G; Dikalov, Sergey I

    2016-06-01

    Vascular superoxide (O˙2 (-)) and inflammation contribute to hypertension. The mitochondria are an important source of O˙2 (-); however, the regulation of mitochondrial O˙2 (-) and the antihypertensive potential of targeting the mitochondria remain poorly defined. Angiotensin II and inflammatory cytokines, such as interleukin 17A and tumor necrosis factor-α (TNFα) significantly contribute to hypertension. We hypothesized that angiotensin II and cytokines co-operatively induce cyclophilin D (CypD)-dependent mitochondrial O˙2 (-) production in hypertension. We tested whether CypD inhibition attenuates endothelial oxidative stress and reduces hypertension. CypD depletion in CypD(-/-) mice prevents overproduction of mitochondrial O˙2 (-) in angiotensin II-infused mice, attenuates hypertension by 20 mm Hg, and improves vascular relaxation compared with wild-type C57Bl/6J mice. Treatment of hypertensive mice with the specific CypD inhibitor Sanglifehrin A reduces blood pressure by 28 mm Hg, inhibits production of mitochondrial O˙2 (-) by 40%, and improves vascular relaxation. Angiotensin II-induced hypertension was associated with CypD redox activation by S-glutathionylation, and expression of the mitochondria-targeted H2O2 scavenger, catalase, abolished CypD S-glutathionylation, prevented stimulation mitochondrial O˙2 (-), and attenuated hypertension. The functional role of cytokine-angiotensin II interplay was confirmed by co-operative stimulation of mitochondrial O˙2 (-) by 3-fold in cultured endothelial cells and impairment of aortic relaxation incubated with combination of angiotensin II, interleukin 17A, and tumor necrosis factor-α which was prevented by CypD depletion or expression of mitochondria-targeted SOD2 and catalase. These data support a novel role of CypD in hypertension and demonstrate that targeting CypD decreases mitochondrial O˙2 (-), improves vascular relaxation, and reduces hypertension. PMID:27067720

  3. Inhibition of late Na+ current, a novel target to improve diastolic function and electrical abnormalities in Dahl salt-sensitive rats.

    PubMed

    Chi, Liguo; Belardinelli, Luiz; Zeng, Aliya; Hirakawa, Ryoko; Rajamani, Sridharan; Ling, Haiyun; Dhalla, Arvinder K

    2016-05-15

    Late Na(+) current (INaL) is enhanced in myocytes of animals with chronic heart failure and patients with hypertrophic cardiomyopathy. To define the role of INaL in diastolic heart failure, the effects of GS-458967 (GS-967), a potent INaL inhibitor on mechanical and electrical abnormalities, were determined in an animal model of diastolic dysfunction. Dahl salt-sensitive (DSS) rats fed a high-salt (HS) diet for 8 wk, compared with a normal salt (NS) diet, had increased left ventricular (LV) mass (1,257 ± 96 vs. 891 ± 34 mg) and diastolic dysfunction [isovolumic relaxation time (IVRT): 26.8 ± 0.5 vs. 18.9 ± 0.2 ms; early transmitral flow velocity/early mitral annulus velocity (E/E') ratio: 25.5 ± 1.9 vs. 14.9 ± 0.9]. INaL in LV myocytes from HS rats was significantly increased to 0.41 ± 0.02 from 0.14 ± 0.02 pA/pF in NS rats. The action potential duration (APD) was prolonged to 136 ± 12 from 68 ± 9 ms in NS rats. QTc intervals were longer in HS vs. NS rats (267 ± 8 vs. 212 ± 2 ms). Acute and chronic treatment with GS-967 decreased the enhanced INaL to 0.24 ± 0.01 and 0.17 ± 0.02 pA/pF, respectively, vs. 0.41 ± 0.02 pA/pF in the HS group. Chronic treatment with GS-967 dose-dependently reduced LV mass, the increases in E/E' ratio, and the prolongation of IVRT by 27, 27, and 20%, respectively, at the 1.0 mg·kg(-1)·day(-1) dose without affecting blood pressure or LV systolic function. The prolonged APDs in myocytes and QTc of HS rats were significantly reduced with GS-967 treatment. These results indicate that INaL is a significant contributor to the LV diastolic dysfunction, hypertrophy, and repolarization abnormalities and thus, inhibition of this current is a promising therapeutic target for diastolic heart failure. PMID:26993228

  4. Common variants in the Na(+)-coupled bicarbonate transporter genes and salt sensitivity of blood pressure: the GenSalt study.

    PubMed

    Guo, L; Liu, F; Chen, S; Yang, X; Huang, J; He, J; Jaquish, C E; Zhao, Q; Gu, C C; Hixson, J E; Gu, D

    2016-09-01

    The current study comprehensively examined the association between common variants in the Na(+)-coupled bicarbonate transporter (NCBT) genes and blood pressure (BP) responses to dietary sodium intervention. A 7-day low-sodium followed by a 7-day high-sodium dietary intervention was conducted among 1906 Han participants from rural areas of northern China. Nine BP measurements were obtained at baseline and each intervention using a random-zero sphygmomanometer. A mixed-effect model was used to assess the additive associations of 76 common variants in five NCBT genes, including SLC4A4, SLC4A5, SLC4A7, SLC4A8 and SLC4A10, with salt sensitivity phenotypes. The Bonferroni method was used to adjust for multiple testing. SLC4A4 marker rs4254735 was significantly associated with diastolic BP (DBP) response to low-sodium intervention (P=5.05 × 10(-4)), with mean (95% confidence interval (CI)) response of -2.91 (-3.21, -2.61) and -0.40 (-1.84, 1.05) mmHg for genotype AA and AG, respectively. In addition, BP responses to high-sodium intervention significantly increased with the number of minor C alleles of SLC4A4 marker rs10022637. Mean systolic BP responses among those with genotypes TT, CT and CC were 4.62 (4.29, 4.99), 5.94 (5.31, 6.58) and 6.00 (3.57, 8.43) mmHg (P=1.14 × 10(-4)); mean DBP responses were 1.72 (1.41, 2.03), 3.22 (2.52, 3.92) and 3.94 (1.88, 5.99) mmHg (P=2.26 × 10(-5)) and mean arterial pressure responses were 2.69 (2.40, 2.97), 4.13 (3.57, 4.70) and 4.61 (2.51, 6.71) mmHg (P=2.07 × 10(-6)), respectively. In brief, the present study indicated that common variants in the SLC4A4 gene might contribute to the variation of BP responses to dietary sodium intake in Han Chinese population. PMID:26582410

  5. Modulators of the Vascular Endothelin Receptor in Blood Pressure Regulation and Hypertension

    PubMed Central

    Khalil, Raouf A.

    2010-01-01

    Endothelin (ET) is one of the most investigated molecules in vascular biology. Since its discovery two decades ago, several ET isoforms, receptors, signaling pathways, agonists and antagonists have been identified. ET functions as a potent endothelium-derived vasoconstrictor, but could also play a role in vascular relaxation. In endothelial cells, preproET and big ET are cleaved by ET converting enzymes into ET-1, −2, −3 and −4. These ET isoforms bind with different affinities to ETA and ETB receptors in vascular smooth muscle (VSM), and in turn increase [Ca2+]i, protein kinase C and mitogen-activated protein kinase and other signaling pathways of VSM contraction and cell proliferation. ET also binds to endothelial ETB receptors and stimulates the release of nitric oxide, prostacyclin and endothelium-derived hyperpolarizing factor. ET, via endothelial ETB receptor, could also promote ET re-uptake and clearance. While the effects of ET on vascular reactivity and growth have been thoroughly examined, its role in the regulation of blood pressure and the pathogenesis of hypertension is not clearly established. Elevated plasma and vascular tissue levels of ET have been identified in salt-sensitive hypertension and in moderate to severe hypertension, and ET receptor antagonists have been shown to reduce blood pressure to variable extents in these forms of hypertension. The development of new pharmacological and genetic tools could lead to more effective and specific modulators of the vascular ET system for treatment of hypertension and related cardiovascular disease. PMID:21222646

  6. Effect of Selectively Introducing Arginine and D-Amino Acids on the Antimicrobial Activity and Salt Sensitivity in Analogs of Human Beta-Defensins

    PubMed Central

    Olli, Sudar; Rangaraj, Nandini; Nagaraj, Ramakrishnan

    2013-01-01

    We have examined the antimicrobial activity of C-terminal analogs of human β-defensins HBD-1and-3 wherein lysines have been selectively replaced by L- and D-arginines and L-isoleucine substituted with its D-enantiomer. The analogs exhibited antibacterial and antifungal activities. Physiological concentration of NaCl did not attenuate the activity of the peptides against Gram-negative bacteria considerably, while some attenuation of activity was observed against S. aureus. Variable attenuation of activity was observed in the presence of Ca2+ and Mg2+. Introduction of D-amino acids abrogated the need for a disulfide bridge for exhibiting activity. Confocal images of carboxyfluorescein (CF) labeled peptides indicated initial localization on the membrane and subsequent translocation into the cell. Analogs corresponding to cationic rich segments of human defensins substituted with L- and D-arginine, could be attractive candidates for development as future therapeutic drugs. PMID:24086767

  7. Hippocampal neurogenesis response: What can we expect from two different models of hypertension?

    PubMed

    Pedroso, Daniela; Nunes, Ana R; Diogo, Lucília N; Oudot, Carole; Monteiro, Emília C; Brenner, Catherine; Vieira, Helena L A

    2016-09-01

    Hypertension is associated with cerebrovascular disease, white matter lesion and cognitive deficit, both in experimental models and clinical observations. Furthermore, in non-clinical models it is shown that hippocampus is affected by hypertension and hypoxia. Herein, two distinct hypertension models were used to study neurogenic response in hippocampus. Dahl salt sensitive (DSS) rat model is a genetic based idiopathic model, while chronic intermittent hypoxia (CIH) mimics the hypertension observed in patients with obstructive sleep apnea (OSA). Both models are chronic and trigger hypertension. No macroscopic alterations based on histological analysis were found in hippocampus derived from DSS and CIH exposure rats. Nevertheless, in hippocampus derived from CIH-induced hypertensive rats, there was a decrease on neuronal population (MAP2 and NeuN positive cells) and an increase on astrocytic marker GFAP. Accordingly, a higher increase on Ki67 expressing cells was found in dentate gyrus (DG) region, suggesting an enhancement of cell proliferation, concomitantly with an increase of Nestin staining, which indicates the presence of immature neurons under differentiation. While, in hippocampus of DSS rats with or without high salt diet, there was no remarkable difference indicating potential neuronal loss, astrocytic activation or neurogenesis. Furthermore, in both models hypertension did not alter the levels of expression of the stress response enzyme heme oxygenase-1 in DG. These data indicate that intermittent hypoxia might be the key factor involved in neurogenesis modulation in hippocampus. Furthermore, two hypotheses can be explored: (i) activation of neurogenesis is a response against neuronal loss induced by hypertension and/or hypoxia or (ii) neurogenesis can be directly stimulated by hypoxia as a neuroprotective mechanism. PMID:27235865

  8. Hypertension and aging.

    PubMed

    Buford, Thomas W

    2016-03-01

    Hypertension is a highly prevalent condition with numerous health risks, and the incidence of hypertension is greatest among older adults. Traditional discussions of hypertension have largely focused on the risks for cardiovascular disease and associated events. However, there are a number of collateral effects, including risks for dementia, physical disability, and falls/fractures which are increasingly garnering attention in the hypertension literature. Several key mechanisms - including inflammation, oxidative stress, and endothelial dysfunction - are common to biologic aging and hypertension development and appear to have key mechanistic roles in the development of the cardiovascular and collateral risks of late-life hypertension. The objective of the present review is to highlight the multi-dimensional risks of hypertension among older adults and discuss potential strategies for treatment and future areas of research for improving overall care for older adults with hypertension. PMID:26835847

  9. Cirrhosis and Portal Hypertension

    MedlinePlus

    MENU Return to Web version Cirrhosis and Portal Hypertension Overview What is cirrhosis? In people who have ... lead to coma and death. What is portal hypertension? Normally, blood is carried to the liver by ...

  10. Depression in hypertensive subjects.

    PubMed

    Ramachandran, V; Parikh, G J; Srinivasan, V

    1983-10-01

    168 patients attending hypertension clinic were randomly selected for the study. They were thoroughly investigated using E.C.G., X-ray chest, Urine analysis, Blood sugar, Blood urea, Serum cholesterol, Serum K, Serum Na, Scrum creatinine and Uric acid level. Detailed psychiatric case history and mental examination was carried out. Beck Rating Scale was used to measure the depression. 25% of hypertensive subjects exhibited depressive features and their mean score in Beck Rating scale is 21.76. The mean score of non-depressives is 4.46. All patients were receiving methyl dopa.25 mg. twice or thrice daily with thiazide diuretic. No significant difference in the incidence of depression with the duration of medication was observed.The hypertension was classified into mild, moderate and severe depending on the diastolic pressure. Depression was more frequent in severe hypertensives but not to the statistically significant level.Further hypertensives were classified into:1. Hypertension without organ involvement2. Hypertension with LVH only3. Hypertension with additional organ involvement4. Malignant hypertensionDepression was significantly more frequent in hypertensives with complications and also hypertensives in whom the B.P. remained uncontrolled. As all the patients were on the same drug, the drug effect is common to all; hence, the higher incidence of depression in hypertensives with complications is due to the limitation and distress caused by the illness. PMID:21847301

  11. How Does Circadian Rhythm Impact Salt Sensitivity of Blood Pressure in Mice? A Study in Two Close C57Bl/6 Substrains

    PubMed Central

    Combe, Roy; Mudgett, John; El Fertak, Lahcen; Champy, Marie-france; Ayme-Dietrich, Estelle; Petit-Demoulière, Benoit; Sorg, Tania; Herault, Yann; Madwed, Jeffrey B.; Monassier, Laurent

    2016-01-01

    Background Mouse transgenesis has provided the unique opportunity to investigate mechanisms underlying sodium kidney reabsorption as well as end organ damage. However, understanding mouse background and the experimental conditions effects on phenotypic readouts of engineered mouse lines such as blood pressure presents a challenge. Despite the ability to generate high sodium and chloride plasma levels during high-salt diet, observed changes in blood pressure are not consistent between wild-type background strains and studies. Methods The present work was designed in an attempt to determine guidelines in the field of salt-induced hypertension by recording continuously blood pressure by telemetry in mice submitted to different sodium and potassium loaded diets and changing experimental conditions in both C57BL/6N and C57BL/6J mice strain (Normal salt vs. Low salt vs. High-salt/normal potassium vs. High salt/low potassium, standard vs. modified light cycle, Non-invasive tail cuff blood pressure vs. telemetry). Results In this study, we have shown that, despite a strong blood pressure (BP) basal difference between C57BL/6N and C57BL/6J mice, High salt/normal potassium diet increases BP and heart rate during the active phase only (dark period) in the same extent in both strains. On the other hand, while potassium level has no effect on salt-induced hypertension in C57BL/6N mice, high-salt/low potassium diet amplifies the effect of the high-salt challenge only in C57BL/6J mice. Indeed, in this condition, salt-induced hypertension can also be detected during light period even though this BP increase is lower compared to the one occurring during the dark period. Finally, from a methodological perspective, light cycle inversion has no effect on this circadian BP phenotype and tail-cuff method is less sensitive than telemetry to detect BP phenotypes due to salt challenges. Conclusions Therefore, to carry investigations on salt-induced hypertension in mice, chronic telemetry

  12. The alpha 1 Na(+)-K+ pump of the Dahl salt-sensitive rat exhibits altered Na+ modulation of K+ transport in red blood cells.

    PubMed

    Canessa, M; Romero, J R; Ruiz-Opazo, N; Herrera, V L

    1993-06-01

    The properties of the alpha 1 Na(+)-K+ pump were compared in Dahl salt-sensitive (DS) and salt-resistant (DR) strains by measuring ouabain-sensitive fluxes (mmol/liter cell x hr = FU, Mean +/- SE) in red blood cells (RBCs) and varying internal (i) and external (o) Na+ and K+ concentrations. Kinetic parameters of several modes of operation, i.e., Na+/K+, K+/K+, Na+/Na+ exchanges, were characterized and analyzed for curve-fitting using the Enzfitter computer program. In unidirectional flux studies (n = 12 rats of each strain) into fresh cells incubated in 140 mM Na(+) + 5 mM K+, ouabain-sensitive K+ influx was substantially lower in the DS than in DR RBCs, while ouabain-sensitive Na+ efflux and Nai were similar in both strains. Thus, the coupling ratio between unidirectional Na+:K+ fluxes was significantly higher in DS than in DR cells at similar RBC Na+ content. In the presence of 140 mM Nao, activation of ouabain-sensitive K+ influx by Ko had a lower Km and Vmax in DS as estimated by the Garay equation (N = 2.70 +/- 0.33, Km 0.74 +/- 0.09 mM; Vmax 2.87 +/- 0.09 FU) than in DR rats (N = 1.23 +/- 0.36, Km 2.31 +/- 0.16 mM; Vmax 5.70 +/- 0.52 FU). However, the two kinetic parameters were similar following Nao removal. The activation of ouabain-sensitive K+ influx by Nai had significantly lower Vmax in DS (9.3 +/- 0.4 FU) than in DR (14.5 +/- 0.6 FU) RBCs but similar Km. These data suggest that the low K+ influx in DS cells is caused by a defect in modulation by Nao and Nai. Na+ efflux showed no differences in Nai activation or trans effects by Nao and Ko, thus accounting for the different Na+:K+ coupling ratio in the Dahl strains. Further evidence for the differences in the coupling of ouabain-sensitive fluxes was found in studies of net Na+ and K+ fluxes, where the net ouabain-sensitive Na+ losses showed similar magnitudes in the two Dahl strains while the net ouabain-sensitive K+ gains were significantly greater in the DR than the DS RBCs. Ouabain-sensitive Na

  13. Orexin, cardio-respiratory function, and hypertension

    PubMed Central

    Li, Aihua; Nattie, Eugene

    2014-01-01

    In this review we focus on the role of orexin in cardio-respiratory functions and its potential link to hypertension. (1) Orexin, cardiovascular function, and hypertension. In normal rats, central administration of orexin can induce significant increases in arterial blood pressure (ABP) and sympathetic nerve activity (SNA), which can be blocked by orexin receptor antagonists. In spontaneously hypertensive rats (SHRs), antagonizing orexin receptors can significantly lower blood pressure under anesthetized or conscious conditions. (2) Orexin, respiratory function, and central chemoreception. The prepro-orexin knockout mouse has a significantly attenuated ventilatory CO2 chemoreflex, and in normal rats, central application of orexin stimulates breathing while blocking orexin receptors decreases the ventilatory CO2 chemoreflex. Interestingly, SHRs have a significantly increased ventilatory CO2 chemoreflex relative to normotensive WKY rats and blocking both orexin receptors can normalize this exaggerated response. (3) Orexin, central chemoreception, and hypertension. SHRs have higher ABP and SNA along with an enhanced ventilatory CO2 chemoreflex. Treating SHRs by blocking both orexin receptors with oral administration of an antagonist, almorexant (Almxt), can normalize the CO2 chemoreflex and significantly lower ABP and SNA. We interpret these results to suggest that the orexin system participates in the pathogenesis and maintenance of high blood pressure in SHRs, and the central chemoreflex may be a causal link to the increased SNA and ABP in SHRs. Modulation of the orexin system could be a potential target in treating some forms of hypertension. PMID:24574958

  14. Essential hypertension of Caribbean Hispanics: sodium, renin, and response to therapy.

    PubMed

    Laffer, Cheryl L; Elijovich, Fernando

    2002-01-01

    Little is known about essential hypertension in Hispanic Americans, despite the fact that they are the fastest-growing minority in the United States and have a disproportionate degree of hypertensive target organ damage. The authors studied 89 Caribbean Hispanic hypertensive patients who participated in six double-blind, randomized trials of antihypertensive agents. Demographics, laboratory data, sodium excretion, plasma renin activity, and atrial natriuretic peptide were obtained after 3-4 weeks on placebo. Blood pressure responses to angiotensin-converting enzyme (ACE) inhibitors, beta blockers, calcium channel blockers, hydrochlorothiazide (HCTZ), and fixed combinations of ACE inhibitors and HCTZ, were compared to the placebo values after 8-12 weeks of treatment. Patients had a multiple risk factor profile (obesity and diabetes) and a wide spectrum of blood pressure elevation, left ventricular hypertrophy, and hypertensive renal damage. Urine sodium excretion rates indicated inability to comply with salt restriction in 65% of patients. Plasma renin activity was lower than that of Hispanic normotensive controls, and 62% of patients had low-renin essential hypertension by renin profiling to sodium excretion. On analysis of variance, blood pressure reductions by calcium channel blockers, HCTZ, and ACE inhibitor/HCTZ combinations were significantly greater than that with placebo, while those of ACE inhibitors and beta blockers as monotherapy were not. The authors conclude that essential hypertension of Caribbean Hispanics is associated with multiple risk factors and is largely of the low-renin type. Responses to therapy are consistent with those observed in other populations with the low-renin phenotype and suggest salt-sensitivity of blood pressure in this population. Confirmation of the latter has implications for prevention and treatment of essential hypertension in Hispanics. PMID:12147929

  15. Resveratrol improves survival, hemodynamics and energetics in a rat model of hypertension leading to heart failure.

    PubMed

    Rimbaud, Stéphanie; Ruiz, Matthieu; Piquereau, Jérôme; Mateo, Philippe; Fortin, Dominique; Veksler, Vladimir; Garnier, Anne; Ventura-Clapier, Renée

    2011-01-01

    Heart failure (HF) is characterized by contractile dysfunction associated with altered energy metabolism. This study was aimed at determining whether resveratrol, a polyphenol known to activate energy metabolism, could be beneficial as a metabolic therapy of HF. Survival, ventricular and vascular function as well as cardiac and skeletal muscle energy metabolism were assessed in a hypertensive model of HF, the Dahl salt-sensitive rat fed with a high-salt diet (HS-NT). Resveratrol (18 mg/kg/day; HS-RSV) was given for 8 weeks after hypertension and cardiac hypertrophy were established (which occurred 3 weeks after salt addition). Resveratrol treatment improved survival (64% in HS-RSV versus 15% in HS-NT, p<0.001), and prevented the 25% reduction in body weight in HS-NT (P<0.001). Moreover, RSV counteracted the development of cardiac dysfunction (fractional shortening -34% in HS-NT) as evaluated by echocardiography, which occurred without regression of hypertension or hypertrophy. Moreover, aortic endothelial dysfunction present in HS-NT was prevented in resveratrol-treated rats. Resveratrol treatment tended to preserve mitochondrial mass and biogenesis and completely protected mitochondrial fatty acid oxidation and PPARα (peroxisome proliferator-activated receptor α) expression. We conclude that resveratrol treatment exerts beneficial protective effects on survival, endothelium-dependent smooth muscle relaxation and cardiac contractile and mitochondrial function, suggesting that resveratrol or metabolic activators could be a relevant therapy in hypertension-induced HF. PMID:22028869

  16. A pathway-based network analysis of hypertension-related genes

    NASA Astrophysics Data System (ADS)

    Wang, Huan; Hu, Jing-Bo; Xu, Chuan-Yun; Zhang, De-Hai; Yan, Qian; Xu, Ming; Cao, Ke-Fei; Zhang, Xu-Sheng

    2016-02-01

    Complex network approach has become an effective way to describe interrelationships among large amounts of biological data, which is especially useful in finding core functions and global behavior of biological systems. Hypertension is a complex disease caused by many reasons including genetic, physiological, psychological and even social factors. In this paper, based on the information of biological pathways, we construct a network model of hypertension-related genes of the salt-sensitive rat to explore the interrelationship between genes. Statistical and topological characteristics show that the network has the small-world but not scale-free property, and exhibits a modular structure, revealing compact and complex connections among these genes. By the threshold of integrated centrality larger than 0.71, seven key hub genes are found: Jun, Rps6kb1, Cycs, Creb312, Cdk4, Actg1 and RT1-Da. These genes should play an important role in hypertension, suggesting that the treatment of hypertension should focus on the combination of drugs on multiple genes.

  17. Therapeutic Targeting of Mitochondrial Superoxide in Hypertension

    PubMed Central

    Dikalova, Anna E.; Bikineyeva, Alfiya T.; Budzyn, Klaudia; Nazarewicz, Rafal R.; McCann, Louise; Lewis, William; Harrison, David G.; Dikalov, Sergey I.

    2010-01-01

    Rationale: Superoxide (O2∸) has been implicated in the pathogenesis of many human diseases including hypertension, however commonly employed antioxidants have proven ineffective in clinical trials. It is possible that these agents are not adequately delivered to the subcellular sites of superoxide production. Objective: Because the mitochondria are important sources of reactive oxygen species, we postulated that mitochondrial targeting of superoxide scavenging would have therapeutic benefit. Methods and Results: In this study, we found that the hormone angiotensin II increased endothelial mitochondrial superoxide production. Treatment with the mitochondrial targeted antioxidant mitoTEMPO decreased mitochondrial O2∸, inhibited the total cellular O2∸, reduced cellular NADPH oxidase activity and restored the level of bioavailable NO. These effects were mimicked by overexpressing the mitochondrial MnSOD (SOD2), while SOD2 depletion with siRNA increased both basal and angiotensin II-stimulated cellular O2∸. Treatment of mice in vivo with mitoTEMPO attenuated hypertension when given at the onset of angiotensin II infusion and decreased blood pressure by 30 mm Hg following establishment of both angiotensin II-induced and DOCA-salt hypertension, while a similar dose of non-targeted TEMPOL was not effective. In vivo, mitoTEMPO decreased vascular O2∸, increased vascular NO• production and improved endothelial-dependent relaxation. Interestingly, transgenic mice overexpressing mitochondrial SOD2 demonstrated attenuated angiotensin II-induced hypertension and vascular oxidative stress similar to mice treated with mitoTEMPO. Conclusions: These studies show that mitochondrial O2∸ is important for the development of hypertension and that antioxidant strategies specifically targeting this organelle could have therapeutic benefit in this and possibly other diseases. PMID:20448215

  18. In vitro vascular responsiveness to norepinephrine in experimental portal hypertension.

    PubMed

    Bomzon, A; Jacob, G; Lee, S S; Meddings, J

    1991-02-01

    It has been postulated that loss of response to norepinephrine accounts in part for the portal hypertension, systemic hypotension, and generalised vascular dilatation of chronic liver disease. The in vitro vascular responsiveness to norepinephrine was measured in aortic rings and portal veins excised from four different rat models of hepatic disease with and without portal hypertension, hepatocellular damage, and hyperbilirubinemia--the carbon tetrachloride (CCl4) cirrhotic rat with portal hypertension, the five-week chronic bile duct ligated and resected (CBDL) cirrhotic rat with portal hypertension and hyperbilirubinemia, the 10-day partial ligated portal vein (PVL) portal hypertensive rat without hepatocellular damage and hyperbilirubinemia, and the three-day bile duct ligated (ABDL) rat with acute hepatocellular damage and hyperbilirubinemia but without portal hypertension. Sham-treated or operated groups for each model were also prepared. Vascular reactivity of the aortic rings to norepinephrine was potentiated in the three portal hypertensive groups, and attenuated in the model of acute cholestasis. No consistent pattern of response to norepinephrine was evident in the portal veins. Based upon the presented in vitro data and the discussed limitations of an in vitro study, we conclude that it is unlikely that the loss of response to norepinephrine accounts for the portal hypertension, systemic hypotension, and generalised vascular dilatation of chronic liver disease. PMID:2040106

  19. Rotary antenna attenuator

    NASA Technical Reports Server (NTRS)

    Dickinson, R. M.; Hardy, J. C.

    1969-01-01

    Radio frequency attenuator, having negligible insertion loss at minimum attenuation, can be used for making precise antenna gain measurements. It is small in size compared to a rotary-vane attenuator.

  20. Valproate Induced Hypertensive Urgency

    PubMed Central

    Sivananthan, Mauran

    2016-01-01

    Valproate is a medication used in the treatment of seizures, bipolar disorder, migraines, and behavioral problems. Here we present a case of an 8-year-old boy who presented with hypertensive urgency after initiation of valproate. Primary treatment of his hypertension was ineffective. Blood pressure stabilization was achieved following discontinuation of valproate. Clinicians should be aware of the risk of developing hypertensive urgency with administration of valproate. PMID:27403366

  1. Pediatric endocrine hypertension

    PubMed Central

    Bhavani, Nisha

    2011-01-01

    Endocrine causes of hypertension are rare in children and screening for endocrine hypertension in children should be carried out only after ruling out renal and renovascular causes. Excess levels and/or action of mineralocorticoids associated with low renin levels lead to childhood hypertension and this can be caused by various conditions which are discussed in detail in the article. Childhood pheochromocytomas are being increasingly diagnosed because of the improved application of genetic testing for familial syndromes associated with pheochromocytomas. Adolescents with polycystic ovarian syndrome (PCOS) can also have hypertension associated with their obese phenotype. PMID:22145140

  2. Hypertensive emergencies in pregnancy.

    PubMed

    Vadhera, Rakesh B; Simon, Michelle

    2014-12-01

    Hypertensive disorders of pregnancy complicate 7% to 10% of pregnancies and are among the major causes of maternal and perinatal morbidity and mortality. Recently American College of Obstetricians and Gynecologists Taskforce on Hypertension during Pregnancy modified the diagnosis and management of hypertension in pregnancy, recommending prompt diagnosis, admission, close monitoring, and treatment. They strive to decrease maternal mortality and systemic complications. Labetalol, hydralazine, or nifedipine are considered first-line treatment, and either can be used to stabilize the patient with similar outcomes. Definite treatment is delivery of the fetus and should be considered based on the etiology of the hypertensive crisis and gestational age. PMID:25314092

  3. Epigenetics and arterial hypertension: the challenge of emerging evidence.

    PubMed

    Friso, Simonetta; Carvajal, Cristian A; Fardella, Carlos E; Olivieri, Oliviero

    2015-01-01

    Epigenetic phenomena include DNA methylation, post-translational histone modifications, and noncoding RNAs, as major marks. Although similar to genetic features of DNA for their heritability, epigenetic mechanisms differ for their potential reversibility by environmental and nutritional factors, which make them potentially crucial for their role in complex and multifactorial diseases. The function of these mechanisms is indeed gaining interest in relation to arterial hypertension (AH) with emerging evidence from cell culture and animal models as well as human studies showing that epigenetic modifications have major functions within pathways related to AH. Among epigenetic marks, the role of DNA methylation is mostly highlighted given the primary role of this epigenetic feature in mammalian cells. A lower global methylation was observed in DNA of peripheral blood mononuclear cells of hypertensive patients. Moreover, DNA hydroxymethylation appears modifiable by salt intake in a Dahl salt-sensitive rat model. The specific function of DNA methylation in regulating the expression of AH-related genes at promoter site was described for hydroxysteroid (11-beta) dehydrogenase 2 (HSD11B2), somatic angiotensin converting enzyme (sACE), Na+/K+/2Cl- cotransporter 1 (NKCC1), angiotensinogen (AGT), α-adducin (ADD1), and for other crucial genes in endocrine hypertension. Post-translational histone methylation at different histone 3 lysine residues was also observed to control the expression of genes related to AH as lysine-specific demethylase-1(LSD1), HSD11B2, and epithelial sodium channel subunit α (SCNN1A). Noncoding RNAs including several microRNAs influence genes involved in steroidogenesis and the renin-angiotensin-aldosterone pathway. In the present review, the current knowledge on the relationship between the main epigenetic marks and AH will be presented, considering the challenge of epigenetic patterns being modifiable by environmental factors that may lead toward

  4. Microglia participate in neurogenic regulation of hypertension.

    PubMed

    Shen, Xiao Z; Li, You; Li, Liang; Shah, Kandarp H; Bernstein, Kenneth E; Lyden, Patrick; Shi, Peng

    2015-08-01

    Hypertension is associated with neuroinflammation and increased sympathetic tone. Interference with neuroinflammation by an anti-inflammatory reagent or overexpression of interleukin-10 in the brain was found to attenuate hypertension. However, the cellular mechanism of neuroinflammation, as well as its impact on neurogenic regulation of blood pressure, is unclear. Here, we found that hypertension, induced by either angiotensin II or l-N(G)-nitro-l-arginine methyl ester, is accompanied by microglial activation as manifested by microgliosis and proinflammatory cytokine upregulation. Targeted depletion of microglia significantly attenuated neuroinflammation, glutamate receptor expression in the paraventricular nucleus, plasma vasopressin level, kidney norepinephrine concentration, and blood pressure. Furthermore, when microglia were preactivated and transferred into the brains of normotensive mice, there was a significantly prolonged pressor response to intracerebroventricular injection of angiotensin II, and inactivation of microglia eliminated these effects. These data demonstrate that microglia, the resident immune cells in the brain, are the major cellular factors in mediating neuroinflammation and modulating neuronal excitation, which contributes to the elevated blood pressure. PMID:26056339

  5. How Is Pulmonary Hypertension Diagnosed?

    MedlinePlus

    ... from the NHLBI on Twitter. How Is Pulmonary Hypertension Diagnosed? Your doctor will diagnose pulmonary hypertension (PH) ... To Look for the Underlying Cause of Pulmonary Hypertension PH has many causes, so many tests may ...

  6. Idiopathic Intracranial Hypertension (Pseudotumor Cerebri)

    MedlinePlus

    ... Asked Questions Español Condiciones Chinese Conditions Idiopathic Intracranial Hypertension (Pseudotumor Cerebri) En Español Read in Chinese What is idiopathic intracranial hypertension? Idiopathic intracranial hypertension (IIH) is a disorder that ...

  7. Hypertension in the military patient.

    PubMed

    Hunter, Alys; Holdsworth, D A; D'Arcy, J; Bailey, K; Casadei, B

    2015-09-01

    Hypertension and hypertension-related diseases are a leading cause of morbidity and mortality worldwide. A diagnosis of hypertension can have serious occupational implications for military personnel. This article examines the diagnosis and management of hypertension in military personnel, in the context of current international standards. We consider the consequences of hypertension in the military environment and potential military-specific issues relating to hypertension. PMID:26253125

  8. Obesity and hypertension: mechanisms, cardio-renal consequences, and therapeutic approaches.

    PubMed

    Reisin, Efrain; Jack, Avanelle V

    2009-05-01

    The increasing prevalence of obesity in the industrialized world is causing an alarming epidemic. Almost 70% of American adults are overweight or obese. The link between increasing body weight and hypertension is well established. Obesity hypertension through metabolic, endocrinic, and systemic hemodynamic alteration causes structural vascular and cardiac adaptations that trigger concentric, eccentric left ventricular hypertrophy and electrophysiological changes, which may increase the risk for congestive heart failure and sudden cardiac death as a result of arrhythmias. The increased renal blood flow in conjunction with a decreased renal vascular resistance causes renal hyperperfusion and hyperfiltration. Such changes lead to glomerulomegaly, focal segmental glomerulosclerosis, tubulointerstitial inflammation, and fibrosis that characterize the renal damage in obese hypertensive subjects. We propose that weight reduction, with the addition of other nonpharmacological approaches that included exercise and reduction in alcohol intake, should be the first choice to treat obesity hypertension. Salt restriction may be helpful only in salt-sensitive patients. The benefits of diet in obese patients include improvement of insulin sensitivity, reduction in sympathetic nervous and renin angiotensin system activities, and restoration of leptin sensitivity. As a consequence of these and other metabolic changes, the previously described systemic and renal hemodynamic alterations improved and the cardiovascular and renal morphological changes induced by obesity were lessened. After reviewing the medications available, we believe that owing to the cardiovascular and renal morbidity and mortality that characterized obesity hypertension, the ACEI or ARBs offer the best cardio-renal protection and should be the pharmacologic treatment of choice. If these alone do not control BP adequately, then a low-dose diuretic should be added as a second approach. Although we strongly believe

  9. Chromosome 2p shows significant linkage to antihypertensive response in the British Genetics of Hypertension Study.

    PubMed

    Padmanabhan, Sandosh; Wallace, Chris; Munroe, Patricia B; Dobson, Richard; Brown, Morris; Samani, Nilesh; Clayton, David; Farrall, Martin; Webster, John; Lathrop, Mark; Caulfield, Mark; Dominiczak, Anna F; Connell, John M

    2006-03-01

    There is a lack of consistently linked loci influencing blood pressure and hypertension status, and this may be because of genetic or phenotypic heterogeneity. We hypothesize that stratification of subjects by response to antihypertensive drug groups could be used to stringently define subsets that will have reduced genetic and etiologic heterogeneity, by partitioning contrasting mechanisms of hypertension and, thus, enhancing gene finding. We investigated the British Genetics of Hypertension Study population, which is composed of 2142 severely hypertensive white affected sibling pairs. Nonresponse to antihypertensive therapy was defined as an on-treatment blood pressure of >140/90 mm Hg or a difference between prediagnosis and on-treatment blood pressure of <20 mm Hg. Of the nonresponders, there were 89 sibling pairs (AB) who were both on antihypertensive therapy that inhibit the renin-angiotensin system (angiotensin-converting enzyme inhibitors, angiotensin II type-1 receptor blockers, or beta-blockers), and 76 sibling pairs (CD) who were both on drugs that do not (calcium channel blockers or diuretics). Nonparametric linkage analysis carried out using markers from a 10-cM genome scan and additional "grid tightening" markers showed significant linkage in the AB group on chromosome 2p (logarithm of odds=4.84 at 90.68 Kosambi cM) and suggestive linkage for the CD group on chromosome 10q (logarithm of odds=2.83 at 125.96 Kosambi cM). The AB linkage locus attained genomewide significance after simulation using 10,000 replicates (P=0.005). This locus may contain a gene for the salt-sensitive form of hypertension and/or a pharmacogenetic locus affecting drug response. We have demonstrated for the first time identification of a significant locus by partitioning different pathways of hypertension using drug response. PMID:16391175

  10. Noncirrhotic Portal Hypertension

    PubMed Central

    Rajekar, Harshal; Vasishta, Rakesh K; Chawla, Yogesh K; Dhiman, Radha K

    2011-01-01

    Portal hypertension is characterized by an increase in portal pressure (> 10 mmHg) and could be a result of cirrhosis of the liver or of noncirrhotic diseases. When portal hypertension occurs in the absence of liver cirrhosis, noncirrhotic portal hypertension (NCPH) must be considered. The prognosis of this disease is much better than that of cirrhosis. Noncirrhotic diseases are the common cause of portal hypertension in developing countries, especially in Asia. NCPH is a heterogeneous group of diseases that is due to intrahepatic or extrahepatic etiologies. In general, the lesions in NCPH are vascular in nature and can be classified based on the site of resistance to blood flow. In most cases, these disorders can be explained by endothelial cell lesions, intimal thickening, thrombotic obliterations, or scarring of the intrahepatic portal or hepatic venous circulation. Many different conditions can determine NCPH through the association of these various lesions in various degrees. Many clinical manifestations of NCPH result from the secondary effects of portal hypertension. Patients with NCPH present with upper gastrointestinal bleeding, splenomegaly, ascites after gastrointestinal bleeding, features of hypersplenism, growth retardation, and jaundice due to portal hypertensive biliopathy. Other sequelae include hyperdynamic circulation, pulmonary complications, and other effects of portosystemic collateral circulation like portosystemic encephalopathy. At present, pharmacologic and endoscopic treatments are the treatments of choice for portal hypertension. The therapy of all disorders causing NCPH involves the reduction of portal pressure by pharmacotherapy or portosystemic shunting, apart from prevention and treatment of complications of portal hypertension. PMID:25755321

  11. What Is Pulmonary Hypertension?

    MedlinePlus

    ... Pressure Tools & Resources Stroke More What is Pulmonary Hypertension? Updated:Aug 12,2014 Is pulmonary hypertension different ... content was last reviewed on 08/04/2014. High Blood Pressure • Home • About High Blood Pressure (HBP) Introduction What ...

  12. Hypertension and cognitive function.

    PubMed

    Paglieri, Cristina; Bisbocci, Daniela; Caserta, Mimma; Rabbia, Franco; Bertello, Chiara; Canadè, Antonella; Veglio, Franco

    2008-11-01

    Arterial hypertension, cerebrovascular disease, and dementia are related pathologies. This paper has reviewed comparatively the incidence of arterial hypertension and adult-onset dementia disorders. Hypertension is associated with cerebrovascular disease, which is in turn associated with dementia. It is the most important modifiable risk factor for stroke, which is a recognized cause of vascular dementia. In terms of pathophysiology of hypertensive brain damage, several hypotheses were developed, such as that vascular alterations induced by hypertension can induce lacunar or cortical infarcts and leucoaraiosis, that hypertension is responsible for cerebrovascular disease and acts into the contest of a pre-existing subclinic Alzheimer's disease (AD), that hypertension determines neurobiologic alterations (such as beta-amyloid accumulation) resulting in neuropathologic damage, and that aging and cerebrovascular risk factors act together to cause cerebral capillary degeneration, mitochondrial disruption, reduced glucose oxidation, and reduced ATP synthesis. The consequence of these alterations are neuronal death and dementia. Macroscopic results of these mechanisms are the so-called white matter lesions (WML), the significance of which is analyzed. Increasing clinical evidence suggests a close relationship between the reduction of elevated blood pressure and countering of both vascular dementia and AD. Antihypertensive treatment probably influences cognitive performances and prevents cognitive function alterations and the development of dementia. It is therefore important to evaluate as soon as possible cognitive functions of hypertensive patients. PMID:19021021

  13. DC attenuation meter

    DOEpatents

    Hargrove, Douglas L.

    2004-09-14

    A portable, hand-held meter used to measure direct current (DC) attenuation in low impedance electrical signal cables and signal attenuators. A DC voltage is applied to the signal input of the cable and feedback to the control circuit through the signal cable and attenuators. The control circuit adjusts the applied voltage to the cable until the feedback voltage equals the reference voltage. The "units" of applied voltage required at the cable input is the system attenuation value of the cable and attenuators, which makes this meter unique. The meter may be used to calibrate data signal cables, attenuators, and cable-attenuator assemblies.

  14. Hypertension in the elderly

    PubMed Central

    Lionakis, Nikolaos; Mendrinos, Dimitrios; Sanidas, Elias; Favatas, Georgios; Georgopoulou, Maria

    2012-01-01

    The elderly are the most rapidly growing population group in the world. Data collected over a 30-year period have demonstrated the increasing prevalence of hypertension with age. The risk of coronary artery disease, stroke, congestive heart disease, chronic kidney insufficiency and dementia is also increased in this subgroup of hypertensives. Hypertension in the elderly patients represents a management dilemma to cardiovascular specialists and other practioners. During the last years and before the findings of the Systolic Hypertension in Europe Trial were published, the general medical opinion considered not to decrease blood pressure values similarly to other younger patients, in order to avoid possible ischemic events and poor oxygenation of the organs (brain, heart, kidney). The aim of this review article is to highlight the importance of treating hypertension in aged population in order to improve their quality of life and lower the incidence of the cardiovascular complications. PMID:22655162

  15. Cervical Spondylosis and Hypertension

    PubMed Central

    Peng, Baogan; Pang, Xiaodong; Li, Duanming; Yang, Hong

    2015-01-01

    Abstract Cervical spondylosis and hypertension are all common diseases, but the relationship between them has never been studied. Patients with cervical spondylosis are often accompanied with vertigo. Anterior cervical discectomy and fusion is an effective method of treatment for cervical spondylosis with cervical vertigo that is unresponsive to conservative therapy. We report 2 patients of cervical spondylosis with concomitant cervical vertigo and hypertension who were treated successfully with anterior cervical discectomy and fusion. Stimulation of sympathetic nerve fibers in pathologically degenerative disc could produce sympathetic excitation, and induce a sympathetic reflex to cause cervical vertigo and hypertension. In addition, chronic neck pain could contribute to hypertension development through sympathetic arousal and failure of normal homeostatic pain regulatory mechanisms. Cervical spondylosis may be one of the causes of secondary hypertension. Early treatment for resolution of symptoms of cervical spondylosis may have a beneficial impact on cardiovascular disease risk in patients with cervical spondylosis. PMID:25761188

  16. Dynamic resistance training decreases sympathetic tone in hypertensive ovariectomized rats.

    PubMed

    Shimojo, G L; Palma, R K; Brito, J O; Sanches, I C; Irigoyen, M C; De Angelis, K

    2015-06-01

    The aim of this study was to investigate the effects of resistance exercise training on hemodynamics and cardiac autonomic control in ovariectomized spontaneously hypertensive rats. Female rats were divided into 4 groups: sedentary control (SC), sedentary hypertensive (SH), sedentary hypertensive ovariectomized (SHO), and resistance-trained hypertensive ovariectomized (RTHO). Resistance exercise training was performed on a vertical ladder (5 days/week, 8 weeks) at 40-60% maximal load. Direct arterial pressure was recorded. Vagal and sympathetic tones were measured by heart rate (HR) responses to methylatropine (3 mg/kg, iv) and propranolol (4 mg/kg, iv). Ovariectomy resulted in additional increases in blood pressure in hypertensive rats and was associated with decreased vagal tone. Resistance exercise trained rats had lower mean arterial pressure than untrained rats (RTHO: 159±2.2 vs SHO: 177±3.4 mmHg), as well as resting bradycardia (RTHO: 332±9.0 vs SHO: 356±5 bpm). Sympathetic tone was also lower in the trained group. Moreover, sympathetic tone was positively correlated with resting HR (r=0.7, P<0.05). The additional arterial pressure increase in hypertensive rats caused by ovarian hormone deprivation was attenuated by moderate-intensity dynamic resistance training. This benefit may be associated with resting bradycardia and reduced cardiac sympathetic tone after training, which suggests potential benefits of resistance exercise for the management of hypertension after ovarian hormone deprivation. PMID:25831206

  17. Renal tubular NEDD4-2 deficiency causes NCC-mediated salt-dependent hypertension.

    PubMed

    Ronzaud, Caroline; Loffing-Cueni, Dominique; Hausel, Pierrette; Debonneville, Anne; Malsure, Sumedha Ram; Fowler-Jaeger, Nicole; Boase, Natasha A; Perrier, Romain; Maillard, Marc; Yang, Baoli; Stokes, John B; Koesters, Robert; Kumar, Sharad; Hummler, Edith; Loffing, Johannes; Staub, Olivier

    2013-02-01

    The E3 ubiquitin ligase NEDD4-2 (encoded by the Nedd4L gene) regulates the amiloride-sensitive epithelial Na+ channel (ENaC/SCNN1) to mediate Na+ homeostasis. Mutations in the human β/γENaC subunits that block NEDD4-2 binding or constitutive ablation of exons 6-8 of Nedd4L in mice both result in salt-sensitive hypertension and elevated ENaC activity (Liddle syndrome). To determine the role of renal tubular NEDD4-2 in adult mice, we generated tetracycline-inducible, nephron-specific Nedd4L KO mice. Under standard and high-Na+ diets, conditional KO mice displayed decreased plasma aldosterone but normal Na+/K+ balance. Under a high-Na+ diet, KO mice exhibited hypercalciuria and increased blood pressure, which were reversed by thiazide treatment. Protein expression of βENaC, γENaC, the renal outer medullary K+ channel (ROMK), and total and phosphorylated thiazide-sensitive Na+Cl- cotransporter (NCC) levels were increased in KO kidneys. Unexpectedly, Scnn1a mRNA, which encodes the αENaC subunit, was reduced and proteolytic cleavage of αENaC decreased. Taken together, these results demonstrate that loss of NEDD4-2 in adult renal tubules causes a new form of mild, salt-sensitive hypertension without hyperkalemia that is characterized by upregulation of NCC, elevation of β/γENaC, but not αENaC, and a normal Na+/K+ balance maintained by downregulation of ENaC activity and upregulation of ROMK. PMID:23348737

  18. Hypertension in Malaysia

    PubMed Central

    Naing, Cho; Yeoh, Peng Nam; Wai, Victor Nyunt; Win, Ni Ni; Kuan, Lai Pei; Aung, Kyan

    2016-01-01

    Abstract This study aimed to determine trends in prevalence, awareness, and control of hypertension in Malaysia and to assess the relationship between socioeconomic determinants and prevalence of hypertension in Malaysia. The distribution of hypertension in Malaysia was assessed based on available data in 3 National Health and Morbidity Surveys (NHMSs) and 1 large scale non-NHMS during the period of 1996 to 2011. Summary statistics was used to characterize the included surveys. Differences in prevalence, awareness, and control of hypertension between any 2 surveys were expressed as ratios. To assess the independent associations between the predictors and the outcome variables, regression analyses were employed with prevalence of hypertension as an outcome variable. Overall, there was a rising trend in the prevalence of hypertension in adults ≥30 years: 32.9% (30%–35.8%) in 1996, 42.6% (37.5%–43.5%) in 2006, and 43.5% (40.4%–46.6%) in 2011. There were significant increase of 32% from 1996 to 2011 (P < 0.001) and of 29% from 1996 to 2006 (P < 0.05), but only a small change of 1% from 2006 to 2011 (P = 0.6). For population ≥18 years, only a 1% increase in prevalence of hypertension occurred from the 2006 NHMS (32.2%) to the 2011 NHMS (32.7%) (P = 0.25). A relative increase of 13% occurred in those with primary education (P < 0.001) and a 15% increase was seen in those with secondary education (P < 0.001). The rate of increase in the prevalence of hypertension in the population with income level RM 3000–3999 was the highest (18%) during this period. In general, the older age group had higher prevalence of hypertension in the 2006 and 2011 NHMSs. The prevalence peaked at 74.1% among population aged 65 to 69 years in the 2011 NHMS. Both the proportion of awareness and the control of hypertension in Malaysia improved from 1996 to 2006. A change in the control of hypertension was 13% higher in women than in men. The findings suggest that

  19. Resistant hypertension - an update.

    PubMed

    Pasha, K; Towhiduzzaman, M; Manwar, A; Jahan, M U

    2015-04-01

    Patients with hypertension are increasing in Bangladesh. Among these patients a growing number of patients are having resistant hypertension faced by both primary care physicians and specialists. There is no data regarding prevalence of resistant hypertension in Bangladesh, but clinical trials abroad suggests that it is not rare, involving perhaps 20% to 30% of study participants. Cardiovascular risk is undoubtedly increased in such patients and the condition is often complicated by multiple other cardiovascular risk factors such as obesity, sleep apnea, diabetes, and chronic kidney disease. Resistant hypertension is almost always multifactorial in etiology. Successful treatment requires identification and reversal of lifestyle factors contributing to treatment resistance; diagnosis and appropriate treatment of secondary causes of hypertension; and use of effective multi drug regimens. Studies of resistant hypertension are limited by the high cardiovascular risk of patients within this subgroup, which generally precludes safe withdrawal of medications; presence of multiple disease processes and their associated medical therapies, which confound interpretation of study results. Therefore we should concentrate on expanding our knowledge of the causes of resistant hypertension which will allow for more effective prevention and/or treatment which is essential to improve long-term clinical management of this condition. PMID:26007281

  20. Reactive oxygen species as important determinants of medullary flow, sodium excretion, and hypertension

    PubMed Central

    Abe, Michiaki; Mori, Takefumi; O'Connor, Paul M.; Ohsaki, Yusuke; Zheleznova, Nadezhda N.

    2014-01-01

    The physiological evidence linking the production of superoxide, hydrogen peroxide, and nitric oxide in the renal medullary thick ascending limb of Henle (mTAL) to regulation of medullary blood flow, sodium homeostasis, and long-term control of blood pressure is summarized in this review. Data obtained largely from rats indicate that experimentally induced elevations of either superoxide or hydrogen peroxide in the renal medulla result in reduction of medullary blood flow, enhanced Na+ reabsorption, and hypertension. A shift in the redox balance between nitric oxide and reactive oxygen species (ROS) is found to occur naturally in the Dahl salt-sensitive (SS) rat model, where selective reduction of ROS production in the renal medulla reduces salt-induced hypertension. Excess medullary production of ROS in SS rats emanates from the medullary thick ascending limbs of Henle [from both the mitochondria and membrane NAD(P)H oxidases] in response to increased delivery and reabsorption of excess sodium and water. There is evidence that ROS and perhaps other mediators such as ATP diffuse from the mTAL to surrounding vasa recta capillaries, resulting in medullary ischemia, which thereby contributes to hypertension. PMID:25354941

  1. Update in Hypertension Therapy.

    PubMed

    Mankin, Leonard A

    2016-07-01

    Hypertension is the leading cause of early mortality in the world, and reduction of blood pressure can help to reduce that burden. There is an enormous and ever-expanding body of literature on hypertension, with a 2016 Medline search for hypertension retrieving more than 113,000 publications. Recent guidelines from major societies have been published, and often present conflicting recommendations based on the same data. Using a question-and-answer format, this article reviews some of the recent developments and opinions on management of blood pressure and provides practical suggestions for management in the clinical arena. PMID:27235610

  2. Perioperative hypertension management

    PubMed Central

    Varon, Joseph; Marik, Paul E

    2008-01-01

    Perioperative hypertension is commonly encountered in patients that undergo surgery. While attempts have been made to standardize the method to characterize the intraoperative hemodynamics, these methods still vary widely. In addition, there is a lack of consensus concerning treatment thresholds and appropriate therapeutic targets, making absolute recommendations about treatment difficult. Nevertheless, perioperative hypertension requires careful management. When treatment is necessary, therapy should be individualized for the patient. This paper reviews the pharmacologic agents and strategies commonly used in the management of perioperative hypertension. PMID:18827911

  3. Lung Disease and Hypertension

    PubMed Central

    Imaizumi, Yuki; Eguchi, Kazuo; Kario, Kazuomi

    2014-01-01

    Chronic obstructive pulmonary disease (COPD) patients are at a high risk of developing cardiovascular diseases. Airflow limitation is a predictor of future risks of hypertension and cardiovascular events. COPD is now understood as a systemic inflammatory disease, with the focus on inflammation of the lungs. An association between inflammation and sympathetic overactivity has also been reported. In this article, we review the association between chronic lung disease and the risks of hypertension, cardiovascular morbidity, the underlying mechanisms, and the therapeutic approach to hypertension and cardiovascular diseases in patients with lung diseases. PMID:26587450

  4. Hypertension in the athlete.

    PubMed

    Sachtleben, Thomas; Fields, Karl B

    2003-04-01

    Athletes with hypertension are frequently encountered in clinical settings and during preparticipation examinations. This common condition merits special attention in athletes, as they have particular physiologic and sport-specific demands. Awareness of the pressor response to both isometric and isotonic exercise is valuable in managing hypertensive athletes. Recommendations regarding physical activity in hypertensive patients and clearance for sports participation among competitive athletes are reviewed. Nonpharmacologic measures and the use of customary antihypertensives in athletes is essential. However, knowledge of side-effect profiles and possible negative effects on exercise tolerance guide appropriate medication choices. PMID:12831663

  5. Management of Hypertension in CKD: Beyond the Guidelines

    PubMed Central

    Judd, Eric; Calhoun, David A.

    2015-01-01

    Hypertension (HTN) and CKD are closely associated with an intermingled cause and effect relationship. Blood pressure (BP) typically rises with declines in kidney function, and sustained elevations in BP hasten progression of kidney disease. This review addresses current management issues in HTN in patients with CKD including altered circadian rhythm of BP, timing of antihypertensive medication dosing, BP targets, diagnostic challenges in evaluating secondary forms of HTN, and the role of salt restriction in CKD. HTN in patients with CKD is often accompanied by a decrease in the kidney’s ability to remove salt. Addressing this salt sensitivity is critical for the management of HTN in CKD. In addition to the well-established use of an ACEI or angiotensin receptor blocker, dietary salt restriction and appropriate diuretic therapy make up the mainstay of HTN treatment in patients with CKD. Bedtime dosing of antihypertensive medications can restore nocturnal dips in BP, and future clinical practice guidelines may recommend bedtime dosing of 1 or more antihypertensive medications in patients with CKD. PMID:25704348

  6. Role of the kidney in the pathogenesis of hypertension: time for a neo-Guytonian paradigm or a paradigm shift?

    PubMed

    Evans, Roger G; Bie, Peter

    2016-02-01

    The "Guytonian paradigm" places the direct effect of arterial pressure, on renal excretion of salt and water, at the center of long-term control of blood pressure, and thus the pathogenesis of hypertension. It originated in the sixties and remains influential within the field of hypertension research. However, the concept of one central long-term feedback loop, through which arterial pressure is maintained by its influence on renal function, has been questioned. Furthermore, some concepts in the paradigm are undermined by experimental observations. For example, volume retention and increased cardiac output induced by high salt intake do not necessarily lead to increased arterial pressure. Indeed, in multiple models of salt-sensitive hypertension the major abnormality appears to be failure of the vasodilator response to increased cardiac output, seen in salt-resistant animals, rather than an increase in cardiac output itself. There is also evidence that renal control of extracellular fluid volume is driven chiefly by volume-dependent neurohumoral control mechanisms rather than through direct or indirect effects of changes in arterial pressure, compatible with the concept that renal sodium excretion is controlled by parallel actions of different feedback systems, including hormones, reflexes, and renal arterial pressure. Moreover, we still do not fully understand the sequence of events underlying the phenomenon of "whole body autoregulation." Thus the events by which volume retention may develop to hypertension characterized by increased peripheral resistance remain enigmatic. Finally, by definition, animal models of hypertension are not "essential hypertension;" progress in our understanding of essential hypertension depends on new results on system functions in patients. PMID:26582636

  7. Secondary hypertension in adults

    PubMed Central

    Puar, Troy Hai Kiat; Mok, Yingjuan; Debajyoti, Roy; Khoo, Joan; How, Choon How; Ng, Alvin Kok Heong

    2016-01-01

    Secondary hypertension occurs in a significant proportion of adult patients (~10%). In young patients, renal causes (glomerulonephritis) and coarctation of the aorta should be considered. In older patients, primary aldosteronism, obstructive sleep apnoea and renal artery stenosis are more prevalent than previously thought. Primary aldosteronism can be screened by taking morning aldosterone and renin levels, and should be considered in patients with severe, resistant or hypokalaemia-associated hypertension. Symptoms of obstructive sleep apnoea should be sought. Worsening of renal function after starting an angiotensin-converting enzyme inhibitor suggests the possibility of renal artery stenosis. Recognition, diagnosis and treatment of secondary causes of hypertension lead to good clinical outcomes and the possible reversal of end-organ damage, in addition to blood pressure control. As most patients with hypertension are managed at the primary care level, it is important for primary care physicians to recognise these conditions and refer patients appropriately. PMID:27211205

  8. Hypertensive heart disease

    MedlinePlus

    ... failure: pathophysiology and diagnosis. In: Goldman L, Schafer AI, eds. Goldman's Cecil Medicine . 24th ed. Philadelphia, PA: ... Victor RG. Arterial hypertension. In: Goldman L, Schafer AI, eds. Goldman's Cecil Medicine . 24th ed. Philadelphia, PA: ...

  9. Hypertension (High Blood Pressure)

    MedlinePlus

    ... pressure to live. Without it, blood can't flow through our bodies and carry oxygen to our vital organs. But when blood pressure gets too high — a condition called hypertension — it can lead to ...

  10. High Blood Pressure (Hypertension)

    MedlinePlus

    ... Print Page Text Size: A A A Listen High Blood Pressure (Hypertension) Nearly 1 in 3 American adults has high ... weight. How Will I Know if I Have High Blood Pressure? High blood pressure is a silent problem — you ...

  11. Hypertension (High Blood Pressure)

    MedlinePlus

    ... blood pressure with the development of a practical method to measure it. Physicians began to note associations between hypertension and risk of heart failure, stroke, and kidney failure. Although scientists had yet to prove that lowering blood pressure ...

  12. Cost of hypertension treatment.

    PubMed

    Odell, T W; Gregory, M C

    1995-12-01

    A retrospective analysis was conducted of the cost of hypertension care at one internal medicine clinic, looking at the cost of office visits, laboratory tests, and medications. Cost of hypertension care was $947 the first year of treatment, $575 the second year, and $420 per year thereafter. Drug costs were the major determinant of cost of care, comprising 80% of the total cost of treatment after the first year of therapy. PMID:8770721

  13. Hypertensive emergencies of pregnancy.

    PubMed

    Alexander, James M; Wilson, Karen L

    2013-03-01

    Hypertension is commonly encountered in pregnancy and has both maternal and fetal effects. Acute hypertensive crisis most commonly occurs in severe preeclampsia and is associated with maternal stroke, cardiopulmonary decompensation, fetal decompensation due to decreased uterine perfusion, abruption, and stillbirth. Immediate stabilization of the mother including the use of intervenous antihypertensives is required and often delivery is indicated. With appropriate management, maternal and fetal outcomes can be excellent. PMID:23466139

  14. Pressure surge attenuator

    DOEpatents

    Christie, Alan M.; Snyder, Kurt I.

    1985-01-01

    A pressure surge attenuation system for pipes having a fluted region opposite crushable metal foam. As adapted for nuclear reactor vessels and heads, crushable metal foam is disposed to attenuate pressure surges.

  15. Resistant hypertension and chronotherapy.

    PubMed

    Prkacin, Ingrid; Balenovic, Diana; Djermanovic-Dobrota, Vesna; Lukac, Iva; Drazic, Petra; Pranjic, Iva-Klara

    2015-04-01

    Resistant hypertension is defined as blood pressure that remains above 140/90 mmHg in spite of the continuous use of three antihypertensive agents in optimal dose, including diuretic, and lifestyle changes. According to data from United States of America and Europe, the prevalence ranges from 10 up to 30% in patients with hypertension. Numerous biological and lifestyle factors can contribute to the development of resistant hypertension: medications, volume overload, obesity, diabetes mellitus, older age, renal parenchymal and renovascular disease, primary aldosteronism, obstructive sleep apnea, pheochormocytoma, Cushing's syndrome, thyroid diseases, aortic coarctation. For diagnosing patient's history is important, assessing compliance, regular blood pressure measurement, physical examination, biochemical evaluation and noninvasive imaging. The evaluation including 24h ambulatory monitoring of blood pressure (ABPM) in the identification of "non-dipper" hypertension. Non-dipper has particular importance and the prevalence of abnormally high sleep blood pressure is very often in chronic kidney patients. Therapeutic restoration of normal physiologic blood pressure reduction during night-time sleep (circadial variation) is the most significant independent predictor of decreased risk and the basis for the chronotherapy. The resistant hypertension treatment is achieved with nonpharmacological and pharmacological approach, treating secondary hypertension causes and invasive procedures. PMID:26005390

  16. Resistant Hypertension and Chronotherapy

    PubMed Central

    Prkacin, Ingrid; Balenovic, Diana; Djermanovic-Dobrota, Vesna; Lukac, Iva; Drazic, Petra; Pranjic, Iva-Klara

    2015-01-01

    Resistant hypertension is defined as blood pressure that remains above 140/90 mmHg in spite of the continuous use of three antihypertensive agents in optimal dose, including diuretic, and lifestyle changes. According to data from United States of America and Europe, the prevalence ranges from 10 up to 30% in patients with hypertension. Numerous biological and lifestyle factors can contribute to the development of resistant hypertension: medications, volume overload, obesity, diabetes mellitus, older age, renal parenchymal and renovascular disease, primary aldosteronism, obstructive sleep apnea, pheochormocytoma, Cushing’s syndrome, thyroid diseases, aortic coarctation. For diagnosing patient’s history is important, assessing compliance, regular blood pressure measurement, physical examination, biochemical evaluation and noninvasive imaging. The evaluation including 24h ambulatory monitoring of blood pressure (ABPM) in the identification of “non-dipper” hypertension. Non-dipper has particular importance and the prevalence of abnormally high sleep blood pressure is very often in chronic kidney patients. Therapeutic restoration of normal physiologic blood pressure reduction during night-time sleep (circadial variation) is the most significant independent predictor of decreased risk and the basis for the chronotherapy. The resistant hypertension treatment is achieved with nonpharmacological and pharmacological approach, treating secondary hypertension causes and invasive procedures. PMID:26005390

  17. Hypertension in Adult Survivors of Child Abuse: Observations from the Nurses’ Health Study II

    PubMed Central

    Riley, EH; Wright, RJ; Jun, HJ; Hibert, EN; Rich-Edwards, JW

    2013-01-01

    Background Limited research has shown a possible association between exposure to physical or sexual abuse prior to age 18 and the risk of developing hypertension as an adult. The factors mediating this relationship are unknown. Methods We analyzed questionnaire data from 68 505 female participants in the Nurses’ Health Study II regarding exposure to physical and sexual abuse prior to age 18. Cox proportional hazards regression was used to assess the relationship between abuse exposure and hypertension. Results Sixty-four percent of the participants (n = 41 792) reported physical and/or sexual abuse prior to age 18; 17% reported hypertension. All forms of abuse had a dose-response relationship with hypertension. Adjustments for smoking, alcohol, family history of hypertension, exercise, and oral contraceptives did not alter risk estimates. Adjustment for body mass index (BMI) significantly attenuated the associations between abuse and risk of hypertension and accounted for approximately 50% of the observed association between abuse exposure and hypertension. Women experiencing forced sexual activity as a child and as an adolescent had a 20% increased risk for developing hypertension (95% CI 8–32%) that was independent of BMI. Similarly, women reporting severe physical abuse in childhood and/or adolescence had risk estimates ranging from 14% (95% CI 5–24%) to 22% (95% CI 11–33%). Conclusion Early interpersonal violence may be a widespread risk factor for the development of hypertension in women. BMI is a significant mediator in the relationship between early abuse and adult hypertension. PMID:20445210

  18. Protective effect of 3-n-butylphthalide against hypertensive nephropathy in spontaneously hypertensive rats.

    PubMed

    Zhu, Jun; Zhang, Yantao; Yang, Changhai

    2015-02-01

    Previous studies have demonstrated that a natural product of celery seeds, 3‑n‑butylphthalide (NBP), has significant antihypertensive effects that are widely utilized in Chinese traditional medicine. The present study aimed to investigate the effects of NBP on hypertensive nephropathy, as well as the mechanisms underlying this disease in spontaneously hypertensive rats (SHRs). SHRs were treated orally with saline, NBP (15 or 30 mg/kg) or losartan (10 mg/kg) daily for 20 weeks, during which time blood pressure was measured every four weeks. At the end of the 20‑week treatment, blood and urine samples were collected for biochemical analysis, and kidney tissues were obtained for histopathological analysis and immunohistochemistry. Enzyme‑linked immunosorbent assays and western blotting were used to analyze the expression of transforming growth factor (TGF)‑β1 in blood and kidney tissues, respectively. The results showed that NBP effectively attenuated progression of hypertensive nephropathy by decreasing urinary albumin excretion and blood urea nitrogen levels. It significantly decreased blood pressure (although less markedly than losartan) and the incidence of glomerulosclerosis. In addition, it alleviated tubular impairment and significantly decreased oxidative stress, as well as the expression of pro‑inflammatory cytokines and TGF-‑β1 in kidney tissues. In conclusion, the results suggested that NBP may slow the progression of hypertensive nephropathy by a variety of mechanisms. PMID:25352064

  19. Tracer attenuation in groundwater

    NASA Astrophysics Data System (ADS)

    Cvetkovic, Vladimir

    2011-12-01

    The self-purifying capacity of aquifers strongly depends on the attenuation of waterborne contaminants, i.e., irreversible loss of contaminant mass on a given scale as a result of coupled transport and transformation processes. A general formulation of tracer attenuation in groundwater is presented. Basic sensitivities of attenuation to macrodispersion and retention are illustrated for a few typical retention mechanisms. Tracer recovery is suggested as an experimental proxy for attenuation. Unique experimental data of tracer recovery in crystalline rock compare favorably with the theoretical model that is based on diffusion-controlled retention. Non-Fickian hydrodynamic transport has potentially a large impact on field-scale attenuation of dissolved contaminants.

  20. [Hypertensive crisis in kidney patients].

    PubMed

    Scrivano, Jacopo; Giuliani, Anna; Pettorini, Laura; Punzo, Giorgio; Mene', Paolo; Pirozzi, Nicola

    2011-01-01

    The classification and management of hypertensive crisis have been recently reviewed in the context of both European and American guidelines. The key points for proper blood pressure control in severe arterial hypertension are: 1 - Distinction between urgent intervention and emergencies 2 - Choice of the best drug(s) 3 - Choice of the correct route of administration. In patients with renal disease, beside the common causes of hypertension/ hypertensive crises, kidney-specific causes should be taken into account such as renal parenchymal hypertension, renovascular hypertension, sclerodermic crises, and preeclampsia. PMID:22028263

  1. Perivascular adipose tissue, vascular reactivity and hypertension.

    PubMed

    Oriowo, Mabayoje A

    2015-01-01

    Most blood vessels are surrounded by a variable amount of adventitial adipose tissue, perivascular adipose tissue (PVAT), which was originally thought to provide mechanical support for the vessel. It is now known that PVAT secretes a number of bioactive substances including vascular endothelial growth factor, tumor necrosis factor-alpha (TNF-α), leptin, adiponectin, insulin-like growth factor, interleukin-6, plasminogen activator substance, resistin and angiotensinogen. Several studies have shown that PVAT significantly modulated vascular smooth muscle contractions induced by a variety of agonists and electrical stimulation by releasing adipocyte-derived relaxing (ADRF) and contracting factors. The identity of ADRF is not yet known. However, several vasodilators have been suggested including adiponectin, angiotensin 1-7, hydrogen sulfide and methyl palmitate. The anticontractile effect of PVAT is mediated through the activation of potassium channels since it is abrogated by inhibiting potassium channels. Hypertension is characterized by a reduction in the size and amount of PVAT and this is associated with the attenuated anticontractile effect of PVAT in hypertension. However, since a reduction in size and amount of PVAT and the attenuated anticontractile effect of PVAT were already evident in prehypertensive rats with no evidence of impaired release of ADRF, there is the possibility that the anticontractile effect of PVAT was not directly related to an altered function of the adipocytes per se. Hypertension is characterized by low-grade inflammation and infiltration of macrophages. One of the adipokines secreted by macrophages is TNF-α. It has been shown that exogenously administered TNF-α enhanced agonist-induced contraction of a variety of vascular smooth muscle preparations and reduced endothelium-dependent relaxation. Other procontractile factors released by the PVAT include angiotensin II and superoxide. It is therefore possible that the loss could be due

  2. Pregnancy with Portal Hypertension

    PubMed Central

    Aggarwal, Neelam; Negi, Neha; Aggarwal, Aakash; Bodh, Vijay; Dhiman, Radha K.

    2014-01-01

    Even though pregnancy is rare with cirrhosis and advanced liver disease, but it may co-exist in the setting of non-cirrhotic portal hypertension as liver function is preserved but whenever encountered together is a complex clinical dilemma. Pregnancy in a patient with portal hypertension presents a special challenge to the obstetrician as so-called physiological hemodynamic changes associated with pregnancy, needed for meeting demands of the growing fetus, worsen the portal hypertension thereby putting mother at risk of potentially life-threatening complications like variceal hemorrhage. Risks of variceal bleed and hepatic decompensation increase many fold during pregnancy. Optimal management revolves round managing the portal hypertension and its complications. Thus management of such cases requires multi-speciality approach involving obstetricians experienced in dealing with high risk cases, hepatologists, anesthetists and neonatologists. With advancement in medical field, pregnancy is not contra-indicated in these women, as was previously believed. This article focuses on the different aspects of pregnancy with portal hypertension with special emphasis on specific cause wise treatment options to decrease the variceal bleed and hepatic decompensation. Based on extensive review of literature, management from pre-conceptional period to postpartum is outlined in order to have optimal maternal and perinatal outcomes. PMID:25755552

  3. Novel treatment approaches in hypertensive type 2 diabetic patients

    PubMed Central

    Castro Torres, Yaniel; Katholi, Richard E

    2014-01-01

    Type 2 diabetes mellitus (T2DM) and hypertension represent two common conditions worldwide. Their frequent association with cardiovascular diseases makes management of hypertensive patients with T2DM an important clinical priority. Carvedilol and renal denervation are two promising choices to reduce plasma glucose levels and blood pressure in hypertensive patients with T2DM to reduce future complications and improve clinical outcomes and prognosis. Pathophysiological mechanisms of both options are under investigation, but one of the most accepted is an attenuation in sympathetic nervous system activity which lowers blood pressure and improves insulin sensitivity. Choice of these therapeutic approaches should be individualized based on specific characteristics of each patient. Further investigations are needed to determine when to consider their use in clinical practice. PMID:25126399

  4. Stress and hypertension.

    PubMed Central

    Mustacchi, P.

    1990-01-01

    In susceptible persons emotional stress results in immediate sympathetic stimulation, with a vasomotor response that results in a high-output state and elevated blood pressure; the vasopressor response seems to be transient. There seems to be no longitudinal epidemiologic validation of the attractive hypothesis that transiently elevated blood pressures are the prelude to fixed hypertension, however. The acquisition of hypertension by populations abandoning their traditional mode of living has been attributed to the sociocultural stress inherent in westernization, but these studies usually have not taken into account concomitants of this type of acculturation, such as dietary changes and increased body weight. The inverse relationship of blood pressure levels to education could explain the development of hypertension when aspiration to upward mobility is thwarted. The severity of perceived occupational stress relates inversely to blood pressure, suggesting that familiarity with a job renders the demands made by the work environment more predictable and less threatening in terms of vasopressor response. PMID:2219875

  5. Hypertension and cerebrovascular damage.

    PubMed

    Veglio, Franco; Paglieri, Cristina; Rabbia, Franco; Bisbocci, Daniela; Bergui, Mauro; Cerrato, Paolo

    2009-08-01

    Hypertension is the most important modifiable factor for cerebrovascular disease. Stroke and dementia are growing health problems that have considerable social and economical consequences. Hypertension causes brain lesions by several mechanisms predisposing to lacunar infarctions, leucoaraiosis, and white matter changes as well as to intracerebral haemorrhages. These parenchymal damages determine evident or silent neurological alterations that often precede the onset of cognitive decline. It is important to recognize cerebrovascular disease and, above all, to correlate typical lesions to hypertension. Antihypertensive therapy has shown clinical benefits in primary and secondary prevention of stroke. These drugs represent important instruments against cerebrovascular disease but their effects on cognition are still matter of debate. Cerebral parenchymal and functional damages have to be considered together to make medical intervention more incisive. PMID:19100549

  6. ATROPHIC CARDIOMYOCYTE SIGNALING IN HYPERTENSIVE HEART DISEASE

    PubMed Central

    Kamalov, German; Zhao, Wenyuan; Zhao, Tieqiang; Sun, Yao; Ahokas, Robert A.; Marion, Tony N.; Darazi, Fahed Al; Gerling, Ivan C.; Bhattacharya, Syamal K.; Weber, Karl T.

    2013-01-01

    Cardinal pathologic features of hypertensive heart disease (HHD) include not only hypertrophied cardiomyocytes and foci of scattered microscopic scarring, a footprint of prior necrosis, but also small myocytes ensnared by fibrillar collagen where disuse atrophy with protein degradation would be predicted. Whether atrophic signaling is concordant with the appearance of HHD and involves oxidative and endoplasmic reticulum (ER) stress remains unexplored. Herein, we examine these possibilities focusing on the left ventricle (LV) and cardiomyocytes harvested from hypertensive rats receiving 4 wks aldosterone/salt treatment (ALDOST) alone or together with ZnSO4, a nonvasoactive antioxidant, with the potential to attenuate atrophy and optimize hypertrophy. Compared to untreated age-/sex-/strain-matched controls, ALDOST was accompanied by: a) LV hypertrophy with preserved systolic function; b) concordant cardiomyocyte atrophy (<1000 μm2) found at sites bordering on fibrosis where they were re-expressing β-myosin heavy chain; and c) upregulation of ubiquitin ligases, MuRF1 and atrogin-1, and elevated 8-isoprostane and unfolded protein ER response with mRNA upregulation of stress markers. ZnSO4 cotreatment reduced lipid peroxidation, fibrosis and the number of atrophic myocytes, together with a further increase in cell area and width of atrophied and hypertrophied myocytes, and improved systolic function, but did not attenuate elevated blood pressure. We conclude that atrophic signaling, concordant with hypertrophy, occurs in the presence of a reparative fibrosis and induction of oxidative and ER stress at sites of scarring where myocytes are atrophied. ZnSO4 cotreatment in HHD with ALDOST attenuates the number of atrophic myocytes, optimizes size of atrophied and hypertrophied myocytes, and improves systolic function. PMID:24084216

  7. Atrophic cardiomyocyte signaling in hypertensive heart disease.

    PubMed

    Kamalov, German; Zhao, Wenyuan; Zhao, Tieqiang; Sun, Yao; Ahokas, Robert A; Marion, Tony N; Al Darazi, Fahed; Gerling, Ivan C; Bhattacharya, Syamal K; Weber, Karl T

    2013-12-01

    Cardinal pathological features of hypertensive heart disease (HHD) include not only hypertrophied cardiomyocytes and foci of scattered microscopic scarring, a footprint of prior necrosis, but also small myocytes ensnared by fibrillar collagen where disuse atrophy with protein degradation would be predicted. Whether atrophic signaling is concordant with the appearance of HHD and involves oxidative and endoplasmic reticulum (ER) stress remains unexplored. Herein, we examine these possibilities focusing on the left ventricle and cardiomyocytes harvested from hypertensive rats receiving 4 weeks aldosterone/salt treatment (ALDOST) alone or together with ZnSO₄, a nonvasoactive antioxidant, with the potential to attenuate atrophy and optimize hypertrophy. Compared with untreated age-/sex-/strain-matched controls, ALDOST was accompanied by (1) left ventricle hypertrophy with preserved systolic function; (2) concordant cardiomyocyte atrophy (<1000 μm²) found at sites bordering on fibrosis where they were reexpressing β-myosin heavy chain; and (3) upregulation of ubiquitin ligases, muscle RING-finger protein-1 and atrogin-1, and elevated 8-isoprostane and unfolded protein ER response with messenger RNA upregulation of stress markers. ZnSO₄ cotreatment reduced lipid peroxidation, fibrosis, and the number of atrophic myocytes, together with a further increase in cell area and width of atrophied and hypertrophied myocytes, and improved systolic function but did not attenuate elevated blood pressure. We conclude that atrophic signaling, concordant with hypertrophy, occurs in the presence of a reparative fibrosis and induction of oxidative and ER stress at sites of scarring where myocytes are atrophied. ZnSO₄ cotreatment in HHD with ALDOST attenuates the number of atrophic myocytes, optimizes size of atrophied and hypertrophied myocytes, and improves systolic function. PMID:24084216

  8. Chronic thromboembolic pulmonary hypertension.

    PubMed

    O'Connell, Caroline; Montani, David; Savale, Laurent; Sitbon, Olivier; Parent, Florence; Seferian, Andrei; Bulifon, Sophie; Fadel, Elie; Mercier, Olaf; Mussot, Sacha; Fabre, Dominique; Dartevelle, Philippe; Humbert, Marc; Simonneau, Gérald; Jaïs, Xavier

    2015-12-01

    Chronic thromboembolic pulmonary hypertension (CTEPH) is a form of pulmonary hypertension (PH) characterized by the persistence of thromboembolic obstructing the pulmonary arteries as an organized tissue and the presence of a variable small vessel arteriopathy. The consequence is an increase in pulmonary vascular resistance resulting in progressive right heart failure. CTEPH is classified as group IV pulmonary hypertension according to the WHO classification of pulmonary hypertension. CTEPH is defined as precapillary pulmonary hypertension (mean pulmonary artery pressure ≥ 25 mmHg with a pulmonary capillary wedge pressure ≤ 15 mmHg) associated with mismatched perfusion defects on ventilation-perfusion lung scan and signs of chronic thromboembolic disease on computed tomography pulmonary angiogram and/or conventional pulmonary angiography, in a patient who received at least 3 months of therapeutic anticoagulation. CTEPH as a direct consequence of symptomatic pulmonary embolism (PE) is rare, and a significant number of CTEPH cases develop in the absence of history of PE. Thus, CTEPH should be considered in any patient with unexplained PH. Splenectomy, chronic inflammatory conditions such as inflammatory bowel disease, indwelling catheters and cardiac pacemakers have been identified as associated conditions increasing the risk of CTEPH. Ventilation-perfusion scan (V/Q) is the best test available for establishing the thromboembolic nature of PH. When CTEPH is suspected, patients should be referred to expert centres where pulmonary angiography, right heart catheterization and high-resolution CT scan will be performed to confirm the diagnosis and to assess the operability. Pulmonary endarterectomy (PEA) remains the gold standard treatment for CTEPH when organized thrombi involve the main, lobar or segmental arteries. This operation should only be performed by experienced surgeons in specialized centres. For inoperable patients, current ESC/ERS guidelines for the

  9. Chronic Interactions Between Carotid Baroreceptors and Chemoreceptors in Obesity Hypertension.

    PubMed

    Lohmeier, Thomas E; Iliescu, Radu; Tudorancea, Ionut; Cazan, Radu; Cates, Adam W; Georgakopoulos, Dimitrios; Irwin, Eric D

    2016-07-01

    Carotid bodies play a critical role in protecting against hypoxemia, and their activation increases sympathetic activity, arterial pressure, and ventilation, responses opposed by acute stimulation of the baroreflex. Although chemoreceptor hypersensitivity is associated with sympathetically mediated hypertension, the mechanisms involved and their significance in the pathogenesis of hypertension remain unclear. We investigated the chronic interactions of these reflexes in dogs with sympathetically mediated, obesity-induced hypertension based on the hypothesis that hypoxemia and tonic activation of carotid chemoreceptors may be associated with obesity. After 5 weeks on a high-fat diet, the animals experienced a 35% to 40% weight gain and increases in arterial pressure from 106±3 to 123±3 mm Hg and respiratory rate from 8±1 to 12±1 breaths/min along with hypoxemia (arterial partial pressure of oxygen=81±3 mm Hg) but eucapnia. During 7 days of carotid baroreflex activation by electric stimulation of the carotid sinus, tachypnea was attenuated, and hypertension was abolished before these variables returned to prestimulation values during a recovery period. After subsequent denervation of the carotid sinus region, respiratory rate decreased transiently in association with further sustained reductions in arterial partial pressure of oxygen (to 65±2 mm Hg) and substantial hypercapnia. Moreover, the severity of hypertension was attenuated from 125±2 to 116±3 mm Hg (45%-50% reduction). These findings suggest that hypoxemia may account for sustained stimulation of peripheral chemoreceptors in obesity and that this activation leads to compensatory increases in ventilation and central sympathetic outflow that contributes to neurogenically mediated hypertension. Furthermore, the excitatory effects of chemoreceptor hyperactivity are abolished by chronic activation of the carotid baroreflex. PMID:27160198

  10. Perspectives on research in hypertension.

    PubMed

    Seedat, Y K

    2009-01-01

    This is a review of my published research on hypertension over 45 years on the three main racial groups residing in KwaZulu-Natal and its main city Durban. These three groups are blacks - mainly Zulu, whites and Indians. The research focused mainly on epidemiology, determinants of the aetiology of hypertension, clinical features, varying responses to hypotensive agents among the racial groups, complications that result from hypertension and the control of hypertension. PMID:19287815

  11. Association between pregnancy-related hypertension and severity of hypertension.

    PubMed

    Moreira, L B; Gus, M; Nunes, G; Gonçalves, C B C; Martins, J; Wiehe, M; Fuchs, F D

    2009-06-01

    Hypertension in pregnancy is an emerging sex-specific risk factor for cardiovascular disease and may lead to more severe hypertension after pregnancy. The objectives of this study were to investigate the frequency of pregnancy-related hypertension among patients referred to a hypertension clinic and its association with the severity of hypertension and evidence of end-organ damage. In this cross-sectional study, women with hypertension were submitted to a systematic clinical evaluation. The occurrence of pregnancy-related hypertension was investigated by questionnaire. The association between pregnancy-related hypertension and severity of hypertension (stage 2 according to Seventh Report of the Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure (JNC VII)) and end-organ damage was assessed in a logistic regression model. The mean age, systolic and diastolic blood pressure and body mass index (BMI) of the 768 women examined were 51.6+/-12.7 years, 158.2+/-26.6 mm Hg, 93.8+/-14.3 mm Hg and 29.4+/-5.6 kg/m(2), respectively. The proportion of women with pregnancy-related hypertension was 32.9%. It was significantly associated with hypertension at stage 2 (OR: 1.60, 95% CI: 1.14-2.24; P=0.01) after controlling for confounders. The occurrence of a pregnancy-related hypertension was not associated with evidence of optic fundi abnormalities, left ventricular hypertrophy or abnormalities in kidney function. In conclusion, pregnancy-related hypertension is frequent in women referred to a hypertension clinic, and is associated with severe hypertension but not with evidence of end-organ damage. PMID:19020534

  12. Premenstrual Syndrome and Subsequent Risk of Hypertension in a Prospective Study.

    PubMed

    Bertone-Johnson, Elizabeth R; Whitcomb, Brian W; Rich-Edwards, Janet W; Hankinson, Susan E; Manson, JoAnn E

    2015-12-15

    The prevalence of hypertension is increasing among younger women, and new strategies are needed to identify high-risk women who should be targets for early intervention. Several mechanisms underlying hypertension might also contribute to premenstrual syndrome (PMS), but whether women with PMS have a higher risk of subsequently developing hypertension has not been assessed. We prospectively evaluated this possibility in a substudy of the Nurses' Health Study II. Participants were 1,257 women with clinically significant PMS (1991-2005) and 2,463 age-matched comparison women with few menstrual symptoms. Participants were followed for incident hypertension until 2011. Over 6-20 years, hypertension was reported by 342 women with PMS and 541 women without. After adjustment for age, smoking, body mass index, and other risk factors for hypertension, women with PMS had a hazard ratio for hypertension of 1.4 (95% confidence interval: 1.2, 1.6) compared with women without PMS. Risk was highest for hypertension that occurred before 40 years of age (hazard ratio = 3.3; 95% confidence interval: 1.7, 6.5; P for interaction = 0.0002). The risk associated with PMS was not modified by use of oral contraceptives or antidepressants but was attenuated among women with high intakes of thiamine and riboflavin (P < 0.05). These results suggest that PMS might be associated with future development of hypertension and that this risk may be modifiable. PMID:26601989

  13. Perinatal Resveratrol Supplementation to Spontaneously Hypertensive Rat Dams Mitigates the Development of Hypertension in Adult Offspring.

    PubMed

    Care, Alison S; Sung, Miranda M; Panahi, Sareh; Gragasin, Ferrante S; Dyck, Jason R B; Davidge, Sandra T; Bourque, Stephane L

    2016-05-01

    This study was undertaken to determine whether perinatal maternal resveratrol (Resv)-a phytoalexin known to confer cardiovascular protection-could prevent the development of hypertension and improve vascular function in adult spontaneously hypertensive rat offspring. Dams were fed either a control or Resv-supplemented diet (4 g/kg diet) from gestational day 0.5 until postnatal day 21. Indwelling catheters were used to assess blood pressure and vascular function in vivo; wire myography was used to assess vascular reactivity ex vivo. Perinatal Resv supplementation in dams had no effect on fetal body weights, albeit continued maternal treatment postnatally resulted in growth restriction in offspring by postnatal day 21; growth restriction was no longer evident after 5 weeks of age. Maternal perinatal Resv supplementation prevented the onset of hypertension in adult offspring (-18 mm Hg;P=0.007), and nitric oxide synthase inhibition (withl-NG-nitroarginine methyl ester) normalized these blood pressure differences, suggesting improved nitric oxide bioavailability underlies the hemodynamic alterations in the Resv-treated offspring. In vivo and ex vivo, vascular responses to methylcholine were not different between treatment groups, but prior treatment withl-NG-nitroarginine methyl ester attenuated the vasodilation in untreated, but not Resv-treated adult offspring, suggesting a shift toward nitric oxide-independent vascular control mechanisms in the treated group. Finally, bioconversion of the inactive precursor big endothelin-1 to active endothelin-1 in isolated mesenteric arteries was reduced in Resv-treated offspring (-28%;P<0.05), and this difference could be normalized byl-NG-nitroarginine methyl ester treatment. In conclusion, perinatal maternal Resv supplementation mitigated the development of hypertension and causes persistent alterations in vascular responsiveness in spontaneously hypertensive rats. PMID:26928803

  14. RICE SALT SENSITIVE3 Forms a Ternary Complex with JAZ and Class-C bHLH Factors and Regulates Jasmonate-Induced Gene Expression and Root Cell Elongation[C][W

    PubMed Central

    Toda, Yosuke; Tanaka, Maiko; Ogawa, Daisuke; Kurata, Kyo; Kurotani, Ken-ichi; Habu, Yoshiki; Ando, Tsuyu; Sugimoto, Kazuhiko; Mitsuda, Nobutaka; Katoh, Etsuko; Abe, Kiyomi; Miyao, Akio; Hirochika, Hirohiko; Hattori, Tsukaho; Takeda, Shin

    2013-01-01

    Plasticity of root growth in response to environmental cues and stresses is a fundamental characteristic of land plants. However, the molecular basis underlying the regulation of root growth under stressful conditions is poorly understood. Here, we report that a rice nuclear factor, RICE SALT SENSITIVE3 (RSS3), regulates root cell elongation during adaptation to salinity. Loss of function of RSS3 only moderately inhibits cell elongation under normal conditions, but it provokes spontaneous root cell swelling, accompanied by severe root growth inhibition, under saline conditions. RSS3 is preferentially expressed in the root tip and forms a ternary complex with class-C basic helix-loop-helix (bHLH) transcription factors and JASMONATE ZIM-DOMAIN proteins, the latter of which are the key regulators of jasmonate (JA) signaling. The mutated protein arising from the rss3 allele fails to interact with bHLH factors, and the expression of a significant portion of JA-responsive genes is upregulated in rss3. These results, together with the known roles of JAs in root growth regulation, suggest that RSS3 modulates the expression of JA-responsive genes and plays a crucial role in a mechanism that sustains root cell elongation at appropriate rates under stressful conditions. PMID:23715469

  15. Pulmonary hypertension caused by pulmonary venous hypertension

    PubMed Central

    2014-01-01

    Abstract The effect of pulmonary venous hypertension (PVH) on the pulmonary circulation is extraordinarily variable, ranging from no impact on pulmonary vascular resistance (PVR) to a marked increase. The reasons for this are unknown. Both acutely reversible pulmonary vasoconstriction and pathological remodeling (especially medial hypertrophy and intimal hyperplasia) account for increased PVR when present. The mechanisms involved in vasoconstriction and remodeling are not clearly defined, but increased wall stress, especially in small pulmonary arteries, presumably plays an important role. Myogenic contraction may account for increased vascular tone and also indirectly stimulate remodeling of the vessel wall. Increased wall stress may also directly cause smooth muscle growth, migration, and intimal hyperplasia. Even long-standing and severe pulmonary hypertension (PH) usually abates with elimination of PVH, but PVH-PH is an important clinical problem, especially because PVH due to left ventricular noncompliance lacks definitive therapy. The role of targeted PH therapy in patients with PVH-PH is unclear at this time. Most prospective studies indicate that these medications are not helpful or worse, but there is ample reason to think that a subset of patients with PVH-PH may benefit from phosphodiesterase inhibitors or other agents. A different approach to evaluating possible pharmacologic therapy for PVH-PH may be required to better define its possible utility. PMID:25610595

  16. [Hypertensive emergency and urgence].

    PubMed

    Gegenhuber, Alfons; Lenz, Kurt

    2003-12-01

    DEFINITION, PATHOPHYSIOLOGY, THERAPY: The hypertensive crisis is characterized by a massive, acute rise in blood pressure. Patients with underlying hypertensive disease usually have an increase in systolic blood pressure values > 220 mmHg and diastolic values > 120 mmHg. The severity of the condition, however, is not determined by the absolute blood pressure level but by the magnitude of the acute increase in blood pressure. Thus, in the presence of primarily normotensive baseline values (such as those in eclampsia), even a systolic blood pressure > 170 mmHg may lead to a life-threatening condition. The most important causes are non-compliance (reduction or interruption of therapy), inadequate therapy, endocrine disease, renal (vessel) disease, pregnancy and intoxication (drugs). The management of this condition greatly depends on whether the patient has a hypertensive crisis with organ manifestation (hypertensive emergency) or a crisis without organ manifestation (hypertensive urgency). By documenting the medical history, the medical status and by simple diagnostic procedures, the differential diagnosis can be established at the emergency site within a very short period of time. In the absence of organ manifestations (hypertensive urgency) the patient may have non-specific symptoms such as palpitations, headache, malaise and a general feeling of illness in addition to the increase in blood pressure. In a hypertensive urgency the patient's blood pressure should not be reduced within a few minutes but within a period of 24 to 48 hours. Such adjustment can be achieved on an out-patient basis, however, only if the patient can be followed up adequately for early detection of a renewed attack. In the absence of follow-up facilities, the patient's blood pressure should be reduced over a period of 4 to 6 hours, if necessary in an out-patient emergency service. While intravenous medication is given preference when a rapid effect is desired, oral medication may be used for

  17. Emerging role of hydrogen sulfide in hypertension and related cardiovascular diseases.

    PubMed

    Meng, Guoliang; Ma, Yan; Xie, Liping; Ferro, Albert; Ji, Yong

    2015-12-01

    Hydrogen sulfide (H2 S) has traditionally been viewed as a highly toxic gas; however, recent studies have implicated H2 S as a third member of the gasotransmitter family, exhibiting properties similar to NO and carbon monoxide. Accumulating evidence has suggested that H2 S influences a wide range of physiological and pathological processes, among which blood vessel relaxation, cardioprotection and atherosclerosis have been particularly studied. In the cardiovascular system, H2 S production is predominantly catalyzed by cystathionine γ-lyase (CSE). Decreased endogenous H2 S levels have been found in hypertensive patients and animals, and CSE(-/-) mice develop hypertension with age, suggesting that a deficiency in H2 S contributes importantly to BP regulation. H2 S supplementation attenuates hypertension in different hypertensive animal models. The mechanism by which H2 S was originally proposed to attenuate hypertension was by virtue of its action on vascular tone, which may be related to effects on different ion channels. Both H2 S and NO cause vasodilatation and there is cross-talk between these two molecules to regulate BP. Suppression of oxidative stress may also contribute to antihypertensive effects of H2 S. This review also summarizes the state of research on H2 S and hypertension in China. A better understanding of the role of H2 S in hypertension and related cardiovascular diseases will allow novel strategies to be devised for their treatment. PMID:25204754

  18. Variable laser attenuator

    DOEpatents

    Foltyn, Stephen R.

    1988-01-01

    The disclosure relates to low loss, high power variable attenuators comprng one or more transmissive and/or reflective multilayer dielectric filters. The attenuator is particularly suitable to use with unpolarized lasers such as excimer lasers. Beam attenuation is a function of beam polarization and the angle of incidence between the beam and the filter and is controlled by adjusting the angle of incidence the beam makes to the filter or filters. Filters are selected in accordance with beam wavelength.

  19. Variable laser attenuator

    DOEpatents

    Foltyn, S.R.

    1987-05-29

    The disclosure relates to low loss, high power variable attenuators comprising one or more transmissive and/or reflective multilayer dielectric filters. The attenuator is particularly suitable to use with unpolarized lasers such as excimer lasers. Beam attenuation is a function of beam polarization and the angle of incidence between the beam and the filter and is controlled by adjusting the angle of incidence the beam makes to the filter or filters. Filters are selected in accordance with beam wavelength. 9 figs.

  20. Gender Differences in Hypertension and Hypertension Awareness Among Young Adults

    PubMed Central

    EVERETT, BETHANY; ZAJACOVA, ANNA

    2016-01-01

    Previous research has shown that men have higher levels of hypertension and lower levels of hypertension awareness than women, but it remains unclear if these differences emerge among young adults. Using the National Longitudinal Study of Adolescent to Adult Health (Add Health), this study examines gender differences in hypertension and hypertension awareness among U.S. young adults, with special focus on factors that may contribute to observed disparities (N = 14,497). Our results show that the gender disparities in hypertension status were already evident among men and women in their twenties: women were far less likely to be hypertensive compared to men (12% vs. 27%). The results also reveal very low levels of hypertension awareness among young women (32% of hypertensive women were aware of their status) and even lower levels among men (25%). Finally, this study identifies key factors that contribute to these observed gender disparities. In particular, health care use, while not related to the actual hypertension status, fully explains the gender differences in hypertension awareness. The findings thus suggest that regular medical visits are critical for improving hypertension awareness among young adults and reducing gender disparities in cardiovascular health. PMID:25879259

  1. Oxidative stress and hypertension: Possibility of hypertension therapy with antioxidants

    PubMed Central

    Baradaran, Azar; Nasri, Hamid; Rafieian-Kopaei, Mahmoud

    2014-01-01

    Hypertension is a major risk factor for myocardial infarction, heart failure, stroke, peripheral arterial disease, and aortic aneurysm, and is a cause of chronic kidney disease. Hypertension is often associated with metabolic abnormalities such as diabetes and dyslipidemia, and the rate of these diseases is increasing nowadays. Recently it has been hypothesized that oxidative stress is a key player in the pathogenesis of hypertension. A reduction in superoxide dismutase and glutathione peroxidase activity has been observed in newly diagnosed and untreated hypertensive subjects, which are inversely correlated with blood pressure. Hydrogen peroxide production is also higher in hypertensive subjects. Furthermore, hypertensive patients have higher lipid hydroperoxide production. Oxidative stress is also markedly increased in hypertensive patients with renovascular disease. If oxidative stress is indeed a cause of hypertension, then, antioxidants should have beneficial effects on hypertension control and reduction of oxidative damage should result in a reduction in blood pressure. Although dietary antioxidants may have beneficial effects on hypertension and cardiovascular risk factors, however, antioxidant supplementation has not been shown consistently to be effective and improvement is not usually seen in blood pressure after treatment with single or combination antioxidant therapy in subjects thought to be at high risk of cardiovascular disease. This matter is the main focus of this paper. A list of medicinal plants that have been reported to be effective in hypertension is also presented. PMID:25097610

  2. Hypertension in adolescents.

    PubMed

    Aglony, Marlene; Acevedo, Monica; Ambrosio, Giuseppe

    2009-12-01

    In adults, hypertension has long been perceived as a public health problem. By contrast, its impact in childhood is far less appreciated. In fact, quite often, high blood pressure in children is not even diagnosed. Blood pressure is a vital sign that is routinely obtained during a physical examination of adults, but only very seldom in children. The diagnosis of hypertension in children is complicated because 'normal' blood pressure values vary with age, sex and height. As a consequence, almost 75% of the cases of arterial hypertension and 90% of the cases of prehypertension in children and adolescents are currently undiagnosed. Furthermore, adolescence hypertension is increasing in prevalence as the prevalence of pediatric obesity has increased. Ambulatory blood pressure monitoring is a useful method for risk evaluation in adolescents. In addition to being viewed as an important cardiovascular risk factor in adolescents, elevated blood pressure should prompt a thorough search for other modifiable risk factors that, if treated, might reduce teenagers' risk of developing cardiovascular disease in adulthood. Thus, assessing blood pressure values in children represents one of the most important measurable markers of cardiovascular risk later in life and a major step in preventive medicine. PMID:19954321

  3. Carvedilol in hypertension treatment

    PubMed Central

    Stafylas, Panagiotis C; Sarafidis, Pantelis A

    2008-01-01

    Although β-blockers have been previously shown to effectively reduce blood pressure (BP) and have been used for hypertension treatment for over 40 years, their effect on cardiovascular morbidity and mortality in hypertensive patients remains controversial and its use in uncomplicated hypertension is currently under debate. However, data on the above field derive mainly from studies which were conducted with older agents, such as atenolol and metoprolol, while considerable pharamacokinetic and pharmacodynamic heterogeneity is present within the class of β-blockers. Carvedilol, a vasodilating non-cardioselective β-blocker, is a compound that seems to give the opportunity to the clinician to use a cardioprotective agent without the concerning hemodynamic and metabolic actions of traditional β-blocker therapy. In contrast with conventional β-blockers, carvedilol maintains cardiac output, has a less extended effect on heart rate and reduces BP by decreasing vascular resistance. Further, several studies has shown that carvedilol has a beneficial or at least neutral effect on metabolic parameters, such as glycemic control, insulin sensitivity, and lipid metabolism, suggesting that they could be used in subjects with the metabolic syndrome or diabetes without negative consequences. This article summarizes the distinct pharmacologic, hemodynamic, and metabolic properties of carvedilol in relation to conventional β-blockers, attempting to examine the potential use of this agent for hypertension treatment. PMID:18629377

  4. High Blood Pressure (Hypertension)

    MedlinePlus

    ... For Consumers Consumer Information by Audience For Women High Blood Pressure (Hypertension) Share Tweet Linkedin Pin it More sharing options ... En Español Who is at risk? How is high blood pressure treated? Understanding your blood pressure: What do the ...

  5. Idiopathic pulmonary arterial hypertension.

    PubMed

    Souza, Rogerio; Jardim, Carlos; Humbert, Marc

    2013-10-01

    Idiopathic pulmonary arterial hypertension (IPAH), formerly called primary pulmonary hypertension, is a rare disease (incidence and prevalence rates of approximately one and six cases per million inhabitants, respectively) with different clinical phenotypes. A group of diverse conditions manifest pulmonary arterial hypertension (PAH) and share similar pathological and/or clinical findings with IPAH. By definition, IPAH is diagnosed only after alternative diagnoses have been ruled out. Extensive investigation is needed to determine if PAH is associated with thyroid diseases, infectious diseases, autoimmune conditions, exposure to certain drugs (particularly anorexigens), certain genetic mutations, and so on. The presence of genetic abnormalities and risk factors (such as specific drug exposures) reinforces the "multiple hit" concept for the development of pulmonary hypertension. Fortunately, within the past two decades, therapeutic options have become available for IPAH, resulting in improved survival and clinical outcomes. At least seven different compounds have been registered for PAH treatment. However, even with aggressive PAH-specific therapy, mortality rates remain high (∼40% at 5 years). Given the high mortality rates, the use of combinations of agents that work by different pathways has been advocated (either as "add-on" therapy or initial "up front" therapy). Further, new therapeutic agents and treatment strategies are on the near horizon, aiming to further improve survival from the remarkable progress already seen. PMID:24037625

  6. Pregnancy-Induced Hypertension

    MedlinePlus

    ... upper arm. Then they listen to your blood flow with a stethoscope. High blood pressure (also called hypertension) occurs when your ... is not a good idea if you have high blood pressure during pregnancy. Your body needs salt to keep up the flow of fluid in your body, so you need ...

  7. Hypertension, a health economics perspective.

    PubMed

    Alcocer, Luis; Cueto, Liliana

    2008-06-01

    The economic aspects of hypertension are critical to modern medicine. The medical, economic, and human costs of untreated and inadequately controlled hypertension are enormous. Hypertension is distributed unequally and with iniquity in different countries and regions of the world. Treatment of hypertension requires an investment over many years to prolong disease-free quality years of life. The high prevalence and high cost of the disease impacts on the microeconomics and macroeconomics of countries and regions. The criteria used for inclusion in clinical guidelines for hypertension impact on the cost and cost/utility of diagnosis or treatment. PMID:19124418

  8. Cognitive function in hypertensive children.

    PubMed

    Lande, Marc B; Kupferman, Juan C

    2015-01-01

    Young hypertensive adults demonstrate decreased performance on neurocognitive testing compared with that of normotensive controls. There is emerging, preliminary evidence that children with hypertension also manifest cognitive differences when compared to normotensive controls. These preliminary studies consist mostly of database and single-center studies that focus primarily on differences in neurocognitive test performance and differences in cerebrovascular reactivity between hypertensive and normotensive subjects. Lessons from the literature on cognition in adult hypertensives and experience from the preliminary studies in children informed the design of a current, multicenter, ongoing study of cognition in children with primary hypertension. PMID:25432900

  9. Metformin Reverses Development of Pulmonary Hypertension via Aromatase Inhibition.

    PubMed

    Dean, Afshan; Nilsen, Margaret; Loughlin, Lynn; Salt, Ian P; MacLean, Margaret R

    2016-08-01

    Females are more susceptible to pulmonary arterial hypertension than males, although the reasons remain unclear. The hypoglycemic drug, metformin, is reported to have multiple actions, including the inhibition of aromatase and stimulation of AMP-activated protein kinase. Inhibition of aromatase using anastrazole is protective in experimental pulmonary hypertension but whether metformin attenuates pulmonary hypertension through this mechanism remains unknown. We investigated whether metformin affected aromatase activity and if it could reduce the development of pulmonary hypertension in the sugen 5416/hypoxic rat model. We also investigated its influence on proliferation in human pulmonary arterial smooth muscle cells. Metformin reversed right ventricular systolic pressure, right ventricular hypertrophy, and decreased pulmonary vascular remodeling in the rat. Furthermore, metformin increased rat lung AMP-activated protein kinase signaling, decreased lung and circulating estrogen levels, levels of aromatase, the estrogen metabolizing enzyme; cytochrome P450 1B1 and its transcription factor; the aryl hydrocarbon receptor. In human pulmonary arterial smooth muscle cells, metformin decreased proliferation and decreased estrogen synthesis by decreasing aromatase activity through the PII promoter site of Cyp19a1 Thus, we report for the first time that metformin can reverse pulmonary hypertension through inhibition of aromatase and estrogen synthesis in a manner likely to be mediated by AMP-activated protein kinase. PMID:27296990

  10. Altered central nervous system processing of noxious stimuli contributes to decreased nociceptive responding in individuals at risk for hypertension.

    PubMed

    France, Christopher R; Froese, Shannon A; Stewart, Jesse C

    2002-07-01

    Previous evidence indicates that individuals with hypertension and those at increased risk for the disorder exhibit decreased pain perception. To test the hypothesis that attenuation of nociceptive processing in individuals at genetic risk for hypertension is related to differential central modulation of nociceptive transmission, the present study examined descending modulation, alpha-motoneuron excitability, and temporal summation of nociceptive input in young adults with and without a parental history of hypertension. Nociceptive flexion (NFR) and non-nociceptive Hoffman reflexes were assessed at rest and during performance of a mental arithmetic task. Temporal summation was assessed by examining NFR threshold in response to a series of five electrical pulses delivered at 2 Hz. Compared to participants without a parental history of hypertension, offspring of individuals with hypertension exhibited significantly higher NFR thresholds, suggesting that risk for hypertension may be associated with enhanced activation of central pain inhibition pathways. PMID:12098621

  11. Dimethylarginine Dimethylaminohydrolase1 Is an Organ-Specific Mediator of End Organ Damage in a Murine Model of Hypertension

    PubMed Central

    Sydow, Karsten; Schmitz, Christine; von Leitner, Eike-Christin; von Leitner, Robin; Klinke, Anna; Atzler, Dorothee; Krebs, Christian; Wieboldt, Hartwig; Ehmke, Heimo; Schwedhelm, Edzard; Meinertz, Thomas; Blankenberg, Stefan; Böger, Rainer H.; Magnus, Tim

    2012-01-01

    Background The endogenous nitric oxide synthase inhibitor asymmetric dimethylarginine (ADMA) is an independent predictor of cardiovascular and overall mortality. Moreover, elevated ADMA plasma concentrations are associated with the extent of hypertension. However, data from small-sized clinical trials and experimental approaches using murine transgenic models have revealed conflicting results regarding the impact of ADMA and its metabolizing enzyme dimethylarginine dimethylaminohydrolase (DDAH) in the pathogenesis of hypertension. Methodology/Principal Findings Therefore, we investigated the role of ADMA and DDAH1 in hypertension-induced end organ damage using the uninephrectomized, deoxycorticosterone actetate salt, and angiotensin II-induced hypertension model in human DDAH1 (hDDAH1) overexpressing and wild-type (WT) mice. ADMA plasma concentrations differed significantly between hDDAH1 and WT mice at baseline, but did not significantly change during the induction of hypertension. hDDAH1 overexpression did not protect against hypertension-induced cardiac fibrosis and hypertrophy. In addition, the hypertension-induced impairment of the endothelium-dependent vasorelaxation of aortic segments ex vivo was not significantly attenuated by hDDAH1 overexpression. However, hDDAH1 mice displayed an attenuated hypertensive inflammatory response in renal tissue, resulting in less hypertensive renal injury. Conclusion/Significance Our data reveal that hDDAH1 organ-specifically modulates the inflammatory response in this murine model of hypertension. The lack of protection in cardiac and aortic tissues may be due to DDAH1 tissue selectivity and/or the extent of hypertension by the used combined model. However, our study underlines the potency of hDDAH1 overexpression in modulating inflammatory processes as a crucial step in the pathogenesis of hypertension, which needs further experimental and clinical investigation. PMID:23110194

  12. Hemorheology in complicated hypertension.

    PubMed

    Cicco, G; Vicenti, P; Stingi, G D; Tarallo; Pirrelli, A

    1999-01-01

    During essential and secondary arterial hypertension it is possible to observe changes in microcirculation perfusion associated with a reduction in tissue oxygenation due in part to hemorheological changes such as an increase in blood viscosity or the formation of the red blood cell "rouleaux" which favour an increase in peripheral resistance and can cause or worsen arterial hypertension. We studied 21 healthy subjects (11 male and 10 female aged 42 +/- 4) and 26 hypertensive subjects (14 male and 12 female aged 49 +/- 3). The patients were non smokers and non suffering from respiratory or haemathological pathologies. They were not undergoing antihypertensive or vasodilatory pharmaceutical treatment. The patients suffered from mild hypertension (II WHO) with Peripheral Occlusive Arterial Disease (POAD II "a" acc. to Leriche-Fontaine class.). The patients showed an increase in cholesterolaemia (6.42 +/- 0.81 mmol/l) and trygliceridaemia (2.73 +/- 0.09 mmol/l) at an average level. The patients were studied in standard conditions with a constant temperature of 22 degrees C. We measured SBP, DBP, MBP, and the HR. We also measured the elongation index (EI) (with shear stress range 0.30 to 30 pascals) using LORCA, acc. to Hardeman method (1994), in order to study the erythrocyte deformability and aggregation kinetics in dynamic condition. To evaluate deformability in static conditions we calculated the Erythrocyte Morphologic Index (EMI), acc. to Forconi method, via the bowl/discocyte ratio (for 100 red blood cells fixed in glutaraldehyde at 0.3% and observed with an optical microscope under immersion in glycerol). Peripheral oxygenation was taken transcutaneously (TcpO2). To establish the level of vascular disease we used the Regional Perfusion Index (RPI = TcpO2 foot/TcpO2 subclavean) and doppler guided Winsor Index (WI). The Student "t" test and linear regression were used for the statistical analysis. Our data confirm a reduction in peripheral tissue oxygenation in

  13. Hypertension: the missing WNKs.

    PubMed

    Dbouk, Hashem A; Huang, Chou-Long; Cobb, Melanie H

    2016-07-01

    The With no Lysine [K] (WNK) family of enzymes are central in the regulation of blood pressure. WNKs have been implicated in hereditary hypertension disorders, mainly through control of the activity and levels of ion cotransporters and channels. Actions of WNKs in the kidney have been heavily investigated, and recent studies have provided insight into not only the regulation of these enzymes but also how mutations in WNKs and their interacting partners contribute to hypertensive disorders. Defining the roles of WNKs in the cardiovascular system will provide clues about additional mechanisms by which WNKs can regulate blood pressure. This review summarizes recent developments in the regulation of the WNK signaling cascade and its role in regulation of blood pressure. PMID:27009339

  14. Hypertension in perspective

    PubMed Central

    Terpstra, W.F.; Zijlstra, F.

    2005-01-01

    Decisions about the management of hypertensive patients should not be based on the level of blood pressure alone, but also on the presence of other risk factors, target organ damage and cardiovascular and renal disease. The results of echocardiography and carotid ultrasonography aids in the stratification of absolute cardiovascular risk as recently advocated by the guidelines of the European Society of Hypertension 2003. Therefore, the detection of target organ damage by ultrasound techniques allows an accurate identification of high-risk patients. Cardiovascular risk stratification only based on a simple routine work-up can often underestimate overall risk, thus leading to a potentially inadequate therapeutic management especially of low-medium risk patients. PMID:25696486

  15. [Hypertensive Disorders in Pregnancy].

    PubMed

    Middeke, Martin

    2016-09-01

    In pregnancy, both mother and fetus benefit from blood pressure in normal ranges. There is discrepancy in the normenclature and thresholds for classification of hypertension in pregnancy and for initiation of antihypertensive treatment in different international guidelines. Systolic and diastolic blood pressure values that are associated with normal outcome are notably lower than any recommended treatment threshold in pregnancy. Tight blood pressure control under 85 mmHg diastolic is save and significantly prevents severe maternal hypertension as could be demonstrated in CHIPS. Close blood pressure monitoring comprising modern methods and devices including telemonitoring allows early recognition of risk developments and optimal guidance of antihypertensive therapy starting early in pregnancy. Only a few pharmacological substances are suitable for antihypertensive treatment in pregnancy. PMID:27598915

  16. An update on hypertensive emergencies and urgencies.

    PubMed

    Muiesan, Maria Lorenza; Salvetti, Massimo; Amadoro, Valentina; di Somma, Salvatore; Perlini, Stefano; Semplicini, Andrea; Borghi, Claudio; Volpe, Massimo; Saba, Pier Sergio; Cameli, Matteo; Ciccone, Marco Matteo; Maiello, Maria; Modesti, Pietro Amedeo; Novo, Salvatore; Palmiero, Pasquale; Scicchitano, Pietro; Rosei, Enrico Agabiti; Pedrinelli, Roberto

    2015-05-01

    Severe acute arterial hypertension is usually defined as 'hypertensive crisis', although 'hypertensive emergencies' or 'hypertensive urgencies', as suggested by the Joint National Committee and the European Society of Hypertension, have completely different diagnostic and therapeutic approaches.The prevalence and demographics of hypertensive emergencies and urgencies have changed over the last four decades, but hypertensive emergencies and urgencies are still associated with significant morbidity and mortality.Different scientific societies have repeatedly produced up-to-date guidelines; however, the treatment of hypertensive emergencies and urgencies is still inappropriate, with potential clinical implications.This review focuses on hypertensive emergencies and urgencies management and treatment, as suggested by recent data. PMID:25575271

  17. Renal denervation and hypertension.

    PubMed

    Schlaich, Markus P; Krum, Henry; Sobotka, Paul A; Esler, Murray D

    2011-06-01

    Essential hypertension remains one of the biggest challenges in medicine with an enormous impact on both individual and society levels. With the exception of relatively rare monogenetic forms of hypertension, there is now general agreement that the condition is multifactorial in nature and hence requires therapeutic approaches targeting several aspects of the underlying pathophysiology. Accordingly, all major guidelines promote a combination of lifestyle interventions and combination pharmacotherapy to reach target blood pressure (BP) levels in order to reduce overall cardiovascular risk in affected patients. Although this approach works for many, it fails in a considerable number of patients for various reasons including drug-intolerance, noncompliance, physician inertia, and others, leaving them at unacceptably high cardiovascular risk. The quest for additional therapeutic approaches to safely and effectively manage hypertension continues and expands to the reappraisal of older concepts such as renal denervation. Based on the robust preclinical and clinical data surrounding the role of renal sympathetic nerves in various aspects of BP control very recent efforts have led to the development of a novel catheter-based approach using radiofrequency (RF) energy to selectively target and disrupt the renal nerves. The available evidence from the limited number of uncontrolled hypertensive patients in whom renal denervation has been performed are auspicious and indicate that the procedure has a favorable safety profile and is associated with a substantial and presumably sustained BP reduction. Although promising, a myriad of questions are far from being conclusively answered and require our concerted research efforts to explore the full potential and possible risks of this approach. Here we briefly review the science surrounding renal denervation, summarize the current data on safety and efficacy of renal nerve ablation, and discuss some of the open questions that need

  18. Drug Treatment of Hypertension

    PubMed Central

    Ryan, Douglas R.

    1991-01-01

    Hypertension is an important contributor to cardiovascular disease, which accounts for about half of all deaths in Western societies. Proper control of elevated blood pressure is therefore important. Support has grown for an approach to care in which antihypertensive drug therapy is individually tailored for each patient. Management strategy based on this approach is discussed, and the advantages and disadvantages of the various antihypertensive agents are reviewed. PMID:21229011

  19. Classification of Pulmonary Hypertension.

    PubMed

    Oudiz, Ronald J

    2016-08-01

    The classification of pulmonary hypertension (PH) is an attempt to define subtypes of PH based on clinical presentation, underlying physiology, and treatment implications. Five groups of PH have been defined, and the classification scheme has been refined over the years to guide clinicians in the diagnosis and management of PH. Understanding the classification of PH is paramount before embarking on a work-up of patients with PH or suspected PH because treatment and outcome can vary greatly. PMID:27443133

  20. Does this patient have hypertensive encephalopathy?

    PubMed

    Christopoulou, Foteini; Rizos, Evangelos C; Kosta, Paraskevi; Argyropoulou, Maria I; Elisaf, Moses

    2016-05-01

    A 63-year-old man was admitted to our hospital for further investigation and management of brain metastases. The patient was initially presented with a 4-day history of confusion. On the day of admission, the patient was confused, agitated, disorientated in place and time, and had visual disturbances. His blood pressure was repeatedly recorded high, with levels of systolic blood pressure between 170-210 mm Hg. A brain magnetic resonance imaging showed areas of high signal on T2 and fluid-attenuated inversion recovery images, located bilaterally in the white matter of the occipital regions and unilateral in the left frontal lobe, suggestive of posterior reversible encephalopathy syndrome. Aggressive treatment of hypertension resulted in complete resolution of the clinical and radiologic features of the syndrome. PMID:26896240

  1. Portal hypertensive enteropathy

    PubMed Central

    Mekaroonkamol, Parit; Cohen, Robert; Chawla, Saurabh

    2015-01-01

    Portal hypertensive enteropathy (PHE) is a condition that describes the pathologic changes and mucosal abnormalities observed in the small intestine of patients with portal hypertension. This entity is being increasingly recognized and better understood over the past decade due to increased accessibility of the small intestine made possible by the introduction of video capsule endoscopy and deep enteroscopy. Though challenged by its diverse endoscopic appearance, multiple scoring systems have been proposed to classify the endoscopic presentation and grade its severity. Endoscopic findings can be broadly categorized into vascular and non-vascular lesions with many subtypes of both categories. Clinical manifestations of PHE can range from asymptomatic incidental findings to fatal gastrointestinal hemorrhage. Classic endoscopic findings in the setting of portal hypertension may lead to a prompt diagnosis. Occasionally histopathology and cross sectional imaging like computed tomography or magnetic resonance imaging may be helpful in establishing a diagnosis. Management of overt bleeding requires multidisciplinary approach involving hepatologists, endoscopists, surgeons, and interventional radiologists. Adequate resuscitation, reduction of portal pressure, and endoscopic therapeutic intervention remain the main principles of the initial treatment. This article reviews the existing evidence on PHE with emphasis on its classification, diagnosis, clinical manifestations, endoscopic appearance, pathological findings, and clinical management. A new schematic management of ectopic variceal bleed is also proposed. PMID:25729469

  2. [Chronic thromboembolic pulmonary hypertension].

    PubMed

    Zonzin, Pietro; Vizza, Carmine Dario; Favretto, Giuseppe

    2003-10-01

    Chronic thromboembolic pulmonary hypertension is due to unresolved or recurrent pulmonary embolism. In the United States the estimated prevalence is 0.1-0.5% among survived patients with pulmonary embolism. The survival rate at 5 years was 30% among patients with a mean pulmonary artery pressure > 40 mmHg at the time of diagnosis and only 10% among those with a value > 50 mmHg. The interval between the onset of disturbances and the diagnosis may be as long as 3 years. Doppler echocardiography permits to establish the diagnosis of pulmonary hypertension. Radionuclide scanning determines whether pulmonary hypertension has a thromboembolic basis. Right heart catheterization and pulmonary angiography are performed in order to establish the extension and the accessibility to surgery of thrombi and to rule out other causes. The surgical treatment is thromboendarterectomy. A dramatic reduction in the pulmonary vascular resistance can be achieved; corresponding improvements in the NYHA class--from class III or IV before surgery to class I-II after surgery--are usually observed. Patients who are not considered candidates for thromboendarterectomy may be considered candidates for lung transplantation. PMID:14664293

  3. Hypertension in the elderly.

    PubMed

    Coope, J

    1987-08-01

    Hypertension is a common finding in patients aged over 60 years, but the following questions need answering. How dangerous is it? Will lowering the blood pressure reduce the attendant risks? What is the 'cost' of such treatment in terms of side effects, drug-induced disease and health service finance? Two recently completed trials throw light on these problems: EWPHE (European Working Party on Hypertension in the Elderly), a European study based on hospital-clinic attenders, using a diuretic backed up with methyldopa; and HEP (randomized trial of treatment of Hypertension in Elderly Patients in Primary Care), based on general-practice screening in England and Wales using atenolol and bendrofluazide. The results of these trials were compared and the findings were broadly similar in the two studies. Some of the differences may be due to the different selection of patients. It is concluded that elderly patients with sustained blood pressures greater or equal to 170/90 mmHg would benefit from treatment by substantial reduction of stroke. Diuretics or beta-blockers, alone or together, are acceptable treatments in elderly subjects. PMID:3312529

  4. Management of hypertension emergencies.

    PubMed

    Elliott, William J

    2003-12-01

    Although they have become less common, hypertensive emergencies occur with an incidence of approximately 1 to 2/100,000 people per year. Our knowledge about this problem, its pathophysiology, risk factors, and appropriate treatment options has expanded during the past decade. A hypertensive emergency can be declared when an elevated blood pressure is associated with acute target-organ damage. Rapid evaluation and treatment (typically with an intravenously administered agent) should be instituted, usually in an intensive care unit setting, and the patient should be observed carefully during acute blood-pressure lowering. When properly treated, the prognosis for these patients is not nearly as dismal as it was more than 60 years ago, and the initial level of function of target organs (brain, heart, kidneys) is more indicative of an emergency than the actual level of blood pressure. Therapeutic options include the time-tested sodium nitroprusside (which has toxic metabolic products and is contraindicated in pregnancy, tobacco amblyopia, and Leber's optic atrophy); fenoldopam mesylate; and nicardipine. When properly treated, "malignant hypertension" need be considered malignant no longer. PMID:14594569

  5. Managing hypertension by polyphenols.

    PubMed

    Fernández-Arroyo, Salvador; Camps, Jordi; Menendez, Javier A; Joven, Jorge

    2015-06-01

    Some polyphenols, obtained from plants of broad use, induce a favorable endothelial response in hypertension and beneficial effects in the management of other metabolic cardiovascular risks. Previous studies in our laboratories using the calyces of Hibiscus sabdariffa as a source of polyphenols show that significant effects on hypertension are noticeable in humans only when provided in high amounts. Available data are suggestive in animal models and ex vivo experiments, but data in humans are difficult to acquire. Additionally, and despite the low bioavailability of polyphenols, intervention studies provide evidence for the protective effects of secondary plant metabolites. Assumptions on public health benefits are limited by the lack of scientific knowledge, robust data derived from large randomized clinical trials, and an accurate assessment of the bioactive components provided by common foodstuff. Because it is likely that clinical effects are the result of multiple interactions among different polyphenols rather than the isolated action of unique compounds, to provide polyphenol-rich botanical extracts as dietary supplements is a suggestive option. Unfortunately, the lack of patent perspectives for the pharmaceutical industries and the high cost of production and release for alimentary industries will hamper the performance of the necessary clinical trials. Here we briefly discuss whether and how such limitations may complicate the extensive use of plant-derived products in the management of hypertension and which steps are the necessary to deal with the predictable complexity in a possible clinical practice. PMID:25714729

  6. Hypertension in the elderly.

    PubMed

    Robles, Nicolas R; Macias, Juan F

    2015-01-01

    Data collected over a 30-year period have demonstrated the increasing prevalence of hypertension with age. Aging is an inevitable part of life and brings along two inconvenient events: physiologic decline and disease state. High blood pressure (HBP) is an important risk factor for cardiovascular morbidity and mortality, particularly in the elderly. It is a significant and often asymptomatic chronic disease, which requires optimal control and persistent adherence to prescribed medication to reduce the risks of cardiovascular, cerebrovascular and renal disease. Hypertension in the elderly patients represents a management dilemma to geriatric and cardiovascular specialists and other practitioners. Furthermore, with the wide adoption of multiple drug strategies targeting subgroups of hypertensive patients with specific risk conditions to lower blood pressure (BP), difficult questions arise about how aggressive treatment of elderly patients should be. The purpose of the following chapter article is to review the pathophysiology of aging as well as the epidemiology and the clinical assessment of high blood pressure (HBP) in older people. PMID:25761101

  7. Association of Parental Hypertension With Arterial Stiffness in Nonhypertensive Offspring: The Framingham Heart Study.

    PubMed

    Andersson, Charlotte; Quiroz, Rene; Enserro, Danielle; Larson, Martin G; Hamburg, Naomi M; Vita, Joseph A; Levy, Daniel; Benjamin, Emelia J; Mitchell, Gary F; Vasan, Ramachandran S

    2016-09-01

    High arterial stiffness seems to be causally involved in the pathogenesis of hypertension. We tested the hypothesis that offspring of parents with hypertension may display higher arterial stiffness before clinically manifest hypertension, given that hypertension is a heritable condition. We compared arterial tonometry measures in a sample of 1564 nonhypertensive Framingham Heart Study third-generation cohort participants (mean age: 38 years; 55% women) whose parents were enrolled in the Framingham Offspring Study. A total of 468, 715, and 381 participants had 0 (referent), 1, and 2 parents with hypertension. Parental hypertension was associated with greater offspring mean arterial pressure (multivariable-adjusted estimate=2.9 mm Hg; 95% confidence interval, 1.9-3.9, and 4.2 mm Hg; 95% confidence interval, 2.9-5.5, for 1 and 2 parents with hypertension, respectively; P<0.001 for both) and with greater forward pressure wave amplitude (1.6 mm Hg; 95% confidence interval, 0.6-2.7, and 1.9 mm Hg; 95% confidence interval, 0.6-3.2, for 1 and 2 parents with hypertension, respectively; P=0.003 for both). Carotid-femoral pulse wave velocity and augmentation index displayed similar dose-dependent relations with parental hypertension in sex-, age-, and height-adjusted models, but associations were attenuated on further adjustment. Offspring with at least 1 parent in the upper quartile of augmentation index and carotid-femoral pulse wave velocity had significantly higher values themselves (P≤0.02). In conclusion, in this community-based sample of young, nonhypertensive adults, we observed greater arterial stiffness in offspring of parents with hypertension. These observations are consistent with higher vascular stiffness at an early stage in the pathogenesis of hypertension. PMID:27456526

  8. Landing gear noise attenuation

    NASA Technical Reports Server (NTRS)

    Moe, Jeffrey W. (Inventor); Whitmire, Julia (Inventor); Kwan, Hwa-Wan (Inventor); Abeysinghe, Amal (Inventor)

    2011-01-01

    A landing gear noise attenuator mitigates noise generated by airframe deployable landing gear. The noise attenuator can have a first position when the landing gear is in its deployed or down position, and a second position when the landing gear is in its up or stowed position. The noise attenuator may be an inflatable fairing that does not compromise limited space constraints associated with landing gear retraction and stowage. A truck fairing mounted under a truck beam can have a compliant edge to allow for non-destructive impingement of a deflected fire during certain conditions.

  9. RADIO FREQUENCY ATTENUATOR

    DOEpatents

    Giordano, S.

    1963-11-12

    A high peak power level r-f attenuator that is readily and easily insertable along a coaxial cable having an inner conductor and an outer annular conductor without breaking the ends thereof is presented. Spaced first and second flares in the outer conductor face each other with a slidable cylindrical outer conductor portion therebetween. Dielectric means, such as water, contact the cable between the flares to attenuate the radio-frequency energy received thereby. The cylindrical outer conductor portion is slidable to adjust the voltage standing wave ratio to a low level, and one of the flares is slidable to adjust the attenuation level. An integral dielectric container is also provided. (AFC)

  10. Mosaic Attenuation: Etiology, Methods of Differentiation, and Pitfalls.

    PubMed

    Kligerman, Seth J; Henry, Travis; Lin, Cheng T; Franks, Teri J; Galvin, Jeffrey R

    2015-01-01

    Mosaic attenuation is a commonly encountered pattern on computed tomography that is defined as heterogeneous areas of differing lung attenuation. This heterogeneous pattern of attenuation is the result of diverse causes that include diseases of the small airways, pulmonary vasculature, alveoli, and interstitium, alone or in combination. Small airways disease can be a primary disorder, such as respiratory bronchiolitis or constrictive bronchiolitis, or be part of parenchymal lung disease, such as hypersensitivity pneumonitis, or large airways disease, such as bronchiectasis and asthma. Vascular causes resulting in mosaic attenuation are typically chronic thromboembolic pulmonary hypertension, which is characterized by organizing thrombi in the elastic pulmonary arteries, or pulmonary arterial hypertension, a heterogeneous group of diseases affecting the distal pulmonary arterioles. Diffuse ground-glass opacity can result in a mosaic pattern related to a number of processes in acute (eg, infection, pulmonary edema), subacute (eg, organizing pneumonia), or chronic (eg, fibrotic diseases) settings. Imaging clues that can assist the radiologist in pinpointing a diagnosis include evidence of large airway involvement, cardiovascular abnormalities, septal thickening, signs of fibrosis, and demonstration of airtrapping at expiratory imaging. PMID:26274445

  11. Pulmonary Hypertension in Cardiac Surgery

    PubMed Central

    Denault, André; Deschamps, Alain; Tardif, Jean-Claude; Lambert, Jean; Perrault, Louis

    2010-01-01

    Pulmonary hypertension is an important prognostic factor in cardiac surgery associated with increased morbidity and mortality. With the aging population and the associated increase severity of illness, the prevalence of pulmonary hypertension in cardiac surgical patients will increase. In this review, the definition of pulmonary hypertension, the mechanisms and its relationship to right ventricular dysfunction will be presented. Finally, pharmacological and non-pharmacological therapeutic and preventive approaches will be presented. PMID:21286273

  12. Attenuator And Conditioner

    DOEpatents

    Anderson, Gene R.; Armendariz, Marcelino G.; Carson, Richard F.; Bryan, Robert P.; Duckett, III, Edwin B.; Kemme, Shanalyn Adair; McCormick, Frederick B.; Peterson, David W.

    2006-04-04

    An apparatus and method of attenuating and/or conditioning optical energy for an optical transmitter, receiver or transceiver module is disclosed. An apparatus for attenuating the optical output of an optoelectronic connector including: a mounting surface; an array of optoelectronic devices having at least a first end; an array of optical elements having at least a first end; the first end of the array of optical elements optically aligned with the first end of the array of optoelectronic devices; an optical path extending from the first end of the array of optoelectronic devices and ending at a second end of the array of optical elements; and an attenuator in the optical path for attenuating the optical energy emitted from the array of optoelectronic devices. Alternatively, a conditioner may be adapted in the optical path for conditioning the optical energy emitted from the array of optoelectronic devices.

  13. Attenuation of cold stress-induced exacerbation of cardiac and adipose tissue pathology and metabolic disorders in a rat model of metabolic syndrome by the glucocorticoid receptor antagonist RU486

    PubMed Central

    Nagasawa, K; Matsuura, N; Takeshita, Y; Ito, S; Sano, Y; Yamada, Y; Uchinaka, A; Murohara, T; Nagata, K

    2016-01-01

    Objectives: Chronic stress affects the central nervous system as well as endocrine, metabolic and immune systems. However, the effects of cold stress on cardiovascular and metabolic disorders in metabolic syndrome (MetS) have remained unclear. We recently characterized DahlS.Z-Leprfa/Leprfa (DS/obese) rats, derived from a cross between Dahl salt-sensitive and Zucker rats, as a new animal model of MetS. We have now investigated the effects of chronic cold stress and glucocorticoid receptor (GR) blockade on cardiac and adipose tissue pathology as well as on metabolic parameters in this model. Methods: DS/obese rats were exposed to cold stress (immersion in ice-cold water to a depth of 1–2 cm for 2 h per day) with or without subcutaneous injection of the GR antagonist RU486 (2 mg kg−1day−1) for 4 weeks beginning at 9 weeks of age. Age-matched homozygous lean (DahlS.Z-Lepr+/Lepr+) littermates served as a control. Results: Chronic cold stress exacerbated hypertension as well as left ventricular (LV) hypertrophy, fibrosis and diastolic dysfunction in DS/obese rats in a manner sensitive to RU486 treatment. Cold stress with or without RU486 did not affect body weight or fat mass. In contrast, cold stress further increased cardiac oxidative stress as well as macrophage infiltration and proinflammatory gene expression in LV and visceral fat tissue, with all of these effects being attenuated by RU486. Cold stress also further increased GR and 11β-hydroxysteroid dehydrogenase type 1 mRNA and protein abundance in LV and visceral adipose tissue, and these effects were again inhibited by RU486. In addition, RU486 ameliorated the stress-induced aggravation of dyslipidemia, glucose intolerance and insulin resistance in DS/obese rats. Conclusions: Our results implicate GR signaling in cold stress-induced exacerbation of cardiac and adipose tissue pathology as well as of abnormal glucose and lipid metabolism in a rat model of MetS. PMID:27110688

  14. Pharmacologic Treatment of Pediatric Hypertension.

    PubMed

    Dhull, Rachita S; Baracco, Rossana; Jain, Amrish; Mattoo, Tej K

    2016-04-01

    Prevalence of hypertension is increasing in children and adolescents. Uncontrolled hypertension in children not only causes end organ damage but also increases the risk of adult hypertension and cardiovascular disease. Clinical trials have proven efficacy of antihypertensive medications in children. These medications are well tolerated by children with acceptable safety profile. The choice of agent is usually driven by underlying etiology of hypertension, profile of its side effects, and clinician's preference. This article will review currently available pediatric data on mechanism of action, common adverse effects, pediatric indication, recent clinical trial, and newer drugs in the common classes of antihypertensive medications. PMID:27048353

  15. Epidemiology and Genetics of Hypertension.

    PubMed

    Sarkar, Taposh; Singh, Narinder Pal

    2015-09-01

    The prevalence of hypertension is increasing in India as well as in the world. The average prevalence of hypertension in India is 25-30%. The median prevalence of total hypertension in 2009 was 37.6% in men and 40.1% in women in U.S. Hypertension is a major risk factor for majority of patients with cardiovascular, cerebrovascular and renal morbidity and mortality. Environmental factors as well as genetic factors account for regulation of blood pressure and its control. Understanding of genetic factor may not only help in recognising those at risk but also help in treatment. Discovering hypertension susceptibility genes would help recognizing those at risk for developing the disease before the expression of clinical symptoms. Genetic and epidemiological studies have suggested that essential hypertension is a polygenic and multifactorial disorder that results from genetic and/or environmental factors. In India awareness, treatment and control status of hypertension is low, with only half of the urban and a quarter of the rural hypertensive individuals being aware of its presence. In this review we have discussed epidemiology and genetics of hypertension, both the monogenic and polygenic forms. PMID:27608868

  16. Vascular Inflammatory Cells in Hypertension

    PubMed Central

    Harrison, David G.; Marvar, Paul J.; Titze, Jens M.

    2012-01-01

    Hypertension is a common disorder with uncertain etiology. In the last several years, it has become evident that components of both the innate and adaptive immune system play an essential role in hypertension. Macrophages and T cells accumulate in the perivascular fat, the heart and the kidney of hypertensive patients, and in animals with experimental hypertension. Various immunosuppressive agents lower blood pressure and prevent end-organ damage. Mice lacking lymphocytes are protected against hypertension, and adoptive transfer of T cells, but not B cells in the animals restores their blood pressure response to stimuli such as angiotensin II or high salt. Recent studies have shown that mice lacking macrophages have blunted hypertension in response to angiotensin II and that genetic deletion of macrophages markedly reduces experimental hypertension. Dendritic cells have also been implicated in this disease. Many hypertensive stimuli have triggering effects on the central nervous system and signals arising from the circumventricular organ seem to promote inflammation. Studies have suggested that central signals activate macrophages and T cells, which home to the kidney and vasculature and release cytokines, including IL-6 and IL-17, which in turn cause renal and vascular dysfunction and lead to blood pressure elevation. These recent discoveries provide a new understanding of hypertension and provide novel therapeutic opportunities for treatment of this serious disease. PMID:22586409

  17. Hyperuricemia and uncontrolled hypertension in treated hypertensive patients

    PubMed Central

    Cho, Jaelim; Kim, Changsoo; Kang, Dae Ryong; Park, Jeong Bae

    2016-01-01

    Abstract Previous epidemiological studies have suggested that uric acid is an independent risk factor for incident hypertension, whereas few studies have evaluated the effect of hyperuricemia on blood pressure control in hypertensive patients. We investigated whether hyperuricemia predicts uncontrolled hypertension through a large-scale prospective cohort study with hypertensive patients treated with fimasartan in the Republic of Korea (the Kanarb–Metabolic Syndrome study). Of the 10,601 hypertensive patients who were recruited from 582 private clinics and 11 university hospitals at baseline, 7725 completed the follow-up after 3 months of fimasartan medication, and 6506 were included in the analysis after excluding those with missing values. We estimated the risk of uncontrolled hypertension after 3 months (≥130/80 mm Hg in those with diabetes or chronic renal failure and ≥140/90 mm Hg in the remaining patients) related with baseline hyperuricemia (serum uric acid ≥7 mg/dL in males ≥6 mg/dL in females) using multiple logistic regression models. Hyperuricemia increased the risk of uncontrolled hypertension after 3 months of fimasartan medication (odds ratio, 1.247; 95% confidence interval, 1.063–1.462). Males in the highest quartile of uric acid level were at a 1.322 (95% confidence interval, 1.053–1.660) times higher risk of uncontrolled hypertension in reference to the lowest quartile; the same analyses in females were not significant. Patients without metabolic syndrome had significantly higher odds of uncontrolled hypertension with hyperuricemia (odds ratio, 1.328; 95% confidence interval, 1.007–1.751). Hyperuricemia predicted uncontrolled hypertension even after 3 months of fimasartan treatment in hypertensive patients. PMID:27428212

  18. Retinoblastoma-associated protein 140 as a candidate for a novel etiological gene to hypertension.

    PubMed

    Crespo, Kimberley; Ménard, Annie; Deng, Alan Y

    2016-01-01

    Gene discovery in animal models may lead to the revelation of therapeutic targets for essential hypertension as well as mechanistic insights into blood pressure (BP) regulation. Our aim was to identify a disease-causing gene for a component of polygenic hypertension contrasting inbred hypertensive Dahl salt-sensitive (DSS) and normotensive Lewis rats. The chromosome segment harboring a quantitative trait locus (QTL), C16QTL, was first isolated from the rat genome via congenic strains. A candidate gene responsible for C16QTL causing a BP difference between DSS and Lewis rats was then identified using molecular analyses combining our independently-conducted total genome and gene-specific sequencings. The retinoblastoma-associated protein 140 (Rap140)/family with sequence similarity 208 member A (Fam208a) is the only candidate gene supported to be C16QTL among three genes in genome block 1 present in the C16QTL-residing interval. A mode of its actions could be to influence the expressions of genes that are downstream in a pathway potentially leading to BP regulation such as that encoding the solute carrier family 7 (cationic amino acid transporter, y+ system) member 12 (Slc7a12), which is specifically expressed in kidneys. Thus, Rap140/Fam208a probably encoding a transcription factor is the strongest candidate for a novel BP QTL that acts via a putative Rap140/Fam208a-Slc7a12-BP pathway. These data implicate a premier physiological role for Rap140/Fam208 beyond development and a first biological function for the Slc7a12 protein in any organism. PMID:27391979

  19. Cardiovascular effects of the combination of levosimendan and valsartan in hypertensive Dahl/Rapp rats.

    PubMed

    Biala, A; Finckenberg, P; Korpi, A; Loytainen, M; Martonen, E; Levijoki, J; Mervaala, E

    2011-06-01

    Hypertension is the main risk factor for left ventricular hypertrophy and development of diastolic heart failure. There is no yet treatment, which can effectively reduce mortality in patients suffering from heart failure with preserved systolic function. We tested whether the calcium sensitizer levosimendan and the AT1-receptor antagonist valsartan could protect from salt-induced hypertension, cardiovascular mortality and heart failure in Dahl/Rapp salt-sensitive rats fed for 7 weeks with a high salt diet (8% NaCl). Levosimendan (1 mg/kg/day via drinking water) and valsartan (30 mg/kg in the food) monotherapies and their combination prevented mortality in Dahl/Rapp rats. The drug combination evoked an additive effect on blood pressure, cardiac hypertrophy, cardiomyocyte cross-sectional area, target organ damage and myocardial ANP mRNA expression. There was a close correlation between systolic blood pressure and cardiac hypertrophy, cardiac and renal damage. As compared to Dahl/Rapp controls kept on low-salt diet (NaCl 0.3%). The high salt rats exhibited impaired diastolic relaxation as assessed by isovolumic relaxation time. Levosimendan alone and in combination with valsartan, improved diastolic relaxation without significantly improving systolic function. Our findings are evidence for an additive effect between levosimendan and valsartan on blood pressure and a blood pressure-dependent protection against the development of salt-induced target organ damage. The present study also demonstrates that levosimendan, alone or in combination with valsartan, can correct diastolic dysfunction induced by salt-dependent hypertension. PMID:21893687

  20. Fiber Optic Attenuators

    NASA Technical Reports Server (NTRS)

    1995-01-01

    Mike Buzzetti designed a fiber optic attenuator while working at Jet Propulsion Laboratory, intended for use in NASA's Deep Space Network. Buzzetti subsequently patented and received an exclusive license to commercialize the device, and founded Nanometer Technologies to produce it. The attenuator functions without introducing measurable back-reflection or insertion loss, and is relatively insensitive to vibration and changes in temperature. Applications include cable television, telephone networks, other signal distribution networks, and laboratory instrumentation.

  1. Genetics Home Reference: pulmonary arterial hypertension

    MedlinePlus

    ... Primary pulmonary hypertension 2 Primary pulmonary hypertension 3 Primary pulmonary hypertension 4 ClinicalTrials.gov (1 link) ClinicalTrials.gov Scientific articles on PubMed (1 link) PubMed OMIM (4 links) ...

  2. Carotid body potentiation during chronic intermittent hypoxia: implication for hypertension.

    PubMed

    Del Rio, Rodrigo; Moya, Esteban A; Iturriaga, Rodrigo

    2014-01-01

    Autonomic dysfunction is involved in the development of hypertension in humans with obstructive sleep apnea, and animals exposed to chronic intermittent hypoxia (CIH). It has been proposed that a crucial step in the development of the hypertension is the potentiation of the carotid body (CB) chemosensory responses to hypoxia, but the temporal progression of the CB chemosensory, autonomic and hypertensive changes induced by CIH are not known. We tested the hypothesis that CB potentiation precedes the autonomic imbalance and the hypertension in rats exposed to CIH. Thus, we studied the changes in CB chemosensory and ventilatory responsiveness to hypoxia, the spontaneous baroreflex sensitivity (BRS), heart rate variability (HRV) and arterial blood pressure in pentobarbital anesthetized rats exposed to CIH for 7, 14, and 21 days. After 7 days of CIH, CB chemosensory and ventilatory responses to hypoxia were enhanced, while BRS was significantly reduced by 2-fold in CIH-rats compared to sham-rats. These alterations persisted until 21 days of CIH. After 14 days, CIH shifted the HRV power spectra suggesting a predominance of sympathetic over parasympathetic tone. In contrast, hypertension was found after 21 days of CIH. Concomitant changes between the gain of spectral HRV, BRS, and ventilatory hypoxic chemoreflex showed that the CIH-induced BRS attenuation preceded the HRV changes. CIH induced a simultaneous decrease of the BRS gain along with an increase of the hypoxic ventilatory gain. Present results show that CIH-induced persistent hypertension was preceded by early changes in CB chemosensory control of cardiorespiratory and autonomic function. PMID:25429271

  3. Pheochromocytoma induced hypertension.

    PubMed

    Andrews, Deborah

    2010-12-01

    Pheochromocytoma (Pheo) is a rare tumor that develops in the core of a chromaffin cell. This article will focus on pheochromocytoma and its affect on the heart. Because the signs and symptoms of a pheochromocytoma are those of the sympathetic nervous system, this tumor is hard to detect and might not be considered early on. In addition, there are many common deferential diagnoses that may lead to a delay of the correct diagnosis of a pheochromocytoma. Uncontrollable hypertension is one of the primary effects of pheochromocytoma. A severe increase in blood pressure (hypertensive crisis) may occur and this can be a life threatening condition that leads to stroke or arrhythmias. African-Americans are disproportionately affected by hypertension and they often go undiagnosed because of a lack of resources or access to care. This tumor is difficult to detect and its effects often mimic many other diagnoses, which often leads to this tumor being a late consideration. The long-term effects of a pheochromocytoma can lead to damage to the heart muscle, congestive heart failure (CHF), increased risk of diabetes, and even death. Nurses need to be aware of the key signs and symptoms of a pheochromocytoma, and to know when testing for this tumor what symptoms should be considered. Patients who suffer from a diagnosis of this tumor need a lot of emotional support and they must follow a strict diet and medication regimen. Nurses can play a vital role in raising awareness in our community about this tumor as well as being a patient advocate. PMID:21516925

  4. Intracranial Hypertension in Children without Papilledema.

    PubMed

    Chelse, Ana B; Epstein, Leon G

    2015-08-01

    Researchers at Nationwide Children's Hospital studied the frequency of intracranial hypertension without papilledema in children followed in a multispecialty pediatric intracranial hypertension clinic. PMID:26933598

  5. [Chronotherapy in arterial hypertension].

    PubMed

    Bendersky, M

    2015-01-01

    The blood pressure profile in most normo- and hypertensive subjects are currently known, as well as the impact their changes induced on the cardio- and cerebrovascular risk. Ambulatory blood pressure monitoring (ABPM) has contributed greatly to the knowledge of this parameter. It to correct the schedule of drug administration (chronotherapy) with changes in any component of the BP profile that have better correlation with risk. These include the nocturnal decrease and the morning BP surge. Investigations in this direction are still scarce, and multicenter studies need to be conducted that can answer the true preventive impact of such modifications. PMID:26180036

  6. The Immune System in Hypertension

    ERIC Educational Resources Information Center

    Trott, Daniel W.; Harrison, David G.

    2014-01-01

    While hypertension has predominantly been attributed to perturbations of the vasculature, kidney, and central nervous system, research for almost 50 yr has shown that the immune system also contributes to this disease. Inflammatory cells accumulate in the kidneys and vasculature of humans and experimental animals with hypertension and likely…

  7. Exercise hypertension: an adverse prognosis?

    PubMed

    Smith, Ryan G; Rubin, Stanley A; Ellestad, Myrvin H

    2009-01-01

    We sought to clarify the prognostic importance of an "exaggerated" or "hypertensive" systolic blood pressure response to exercise during an exercise test. Studies evaluating the prognosis for cardiovascular events and cardiovascular mortality in those with hypertension during exercise testing were systematically reviewed. Fourteen studies were identified. Six studies were of healthy volunteers or hypertensives. Eight studies were in subjects with known or suspected heart disease. Without established heart disease, exercise hypertension predicted cardiovascular events and cardiovascular death. However, two of the six studies included a multivariate analysis; both demonstrated no independent association. Studies in subjects with known or suspected heart disease demonstrated that exercise hypertension predicted fewer cardiac events and lesser mortality or, after multivariate adjustment, no associated risk. In a healthy population, a higher exercise blood pressure may indicate hypertension or prehypertension, instead of normal vascular function, and an associated long-term adverse prognosis. In a population with a high burden of heart disease, the highest risk subjects with the most extensive cardiac disease may not be capable of generating pressure or workload to allow the manifestation of exercise systolic hypertension. By comparison, therefore, those with exercise hypertension have a better prognosis. PMID:20409979

  8. Endocrine hypertension – Cushing's syndrome

    PubMed Central

    Singh, Yashpal; Kotwal, Narendra; Menon, A. S.

    2011-01-01

    Hypertension is a major and frequent comorbid finding of Cushing's syndrome. This review discusses the etiology and pathophysiology of hypertension in Cushing's syndrome, while suggesting methods of management of this condition. It also provides an overview of diagnosis and management strategies in this disease. PMID:22145133

  9. Obligatory Role for B Cells in the Development of Angiotensin II-Dependent Hypertension.

    PubMed

    Chan, Christopher T; Sobey, Christopher G; Lieu, Maggie; Ferens, Dorota; Kett, Michelle M; Diep, Henry; Kim, Hyun Ah; Krishnan, Shalini M; Lewis, Caitlin V; Salimova, Ekaterina; Tipping, Peter; Vinh, Antony; Samuel, Chrishan S; Peter, Karlheinz; Guzik, Tomasz J; Kyaw, Tin S; Toh, Ban-Hock; Bobik, Alexander; Drummond, Grant R

    2015-11-01

    Clinical hypertension is associated with raised serum IgG antibodies. However, whether antibodies are causative agents in hypertension remains unknown. We investigated whether hypertension in mice is associated with B-cell activation and IgG production and moreover whether B-cell/IgG deficiency affords protection against hypertension and vascular remodeling. Angiotensin II (Ang II) infusion (0.7 mg/kg per day; 28 days) was associated with (1) a 25% increase in the proportion of splenic B cells expressing the activation marker CD86, (2) an 80% increase in splenic plasma cell numbers, (3) a 500% increase in circulating IgG, and (4) marked IgG accumulation in the aortic adventitia. In B-cell-activating factor receptor-deficient (BAFF-R(-/-)) mice, which lack mature B cells, there was no evidence of Ang II-induced increases in serum IgG. Furthermore, the hypertensive response to Ang II was attenuated in BAFF-R(-/-) (Δ30±4 mm Hg) relative to wild-type (Δ41±5 mm Hg) mice, and this response was rescued by B-cell transfer. BAFF-R(-/-) mice displayed reduced IgG accumulation in the aorta, which was associated with 80% fewer aortic macrophages and a 70% reduction in transforming growth factor-β expression. BAFF-R(-/-) mice were also protected from Ang II-induced collagen deposition and aortic stiffening (assessed by pulse wave velocity analysis). Finally, like BAFF-R deficiency, pharmacological depletion of B cells with an anti-CD20 antibody attenuated Ang II-induced hypertension by ≈35%. Hence, these studies demonstrate that B cells/IgGs are crucial for the development of Ang II-induced hypertension and vessel remodeling in mice. Thus, B-cell-targeted therapies-currently used for autoimmune diseases-may hold promise as future treatments for hypertension. PMID:26351030

  10. Inflammatory cytokines in pulmonary hypertension

    PubMed Central

    2014-01-01

    Pulmonary hypertension is an “umbrella term” used for a spectrum of entities resulting in an elevation of the pulmonary arterial pressure. Clinical symptoms include dyspnea and fatigue which in the absence of adequate therapeutic intervention may lead to progressive right heart failure and death. The pathogenesis of pulmonary hypertension is characterized by three major processes including vasoconstriction, vascular remodeling and microthrombotic events. In addition accumulating evidence point to a cytokine driven inflammatory process as a major contributor to the development of pulmonary hypertension. This review summarizes the latest clinical and experimental developments in inflammation associated with pulmonary hypertension with special focus on Interleukin-6, and its role in vascular remodeling in pulmonary hypertension. PMID:24739042

  11. Hypertension in children and adolescents.

    PubMed

    Mitsnefes, Mark M

    2006-06-01

    Hypertension is one of the most common health problems in the United States and a powerful independent risk factor for cardiovascular and renal disease. Until recently, the incidence of persistent hypertension in children has been low, with a range of 1% to 3%. Recent data indicate that over the last decade, however, average blood pressure levels have risen substantially among American children. Obesity and other lifestyle factors, such as physical inactivity and increased intake of high-calorie, high-salt foods, are thought to be responsible for this trend. Hypertension in children is currently recognized as an important health issue. There is increasing evidence that hypertension has its antecedents during childhood, because adult blood pressure often correlates with childhood blood pressure. Hypertension in children also is viewed as a significant risk factor for the development of cardiovascular disease in adulthood. PMID:16716793

  12. Homocysteine and essential hypertension.

    PubMed

    Rodrigo, Ramón; Passalacqua, Walter; Araya, Julia; Orellana, Myriam; Rivera, Gonzalo

    2003-12-01

    The authors examine the available clinical and experimental data supporting the view that homocysteine, an alternative risk factor of cardiovascular disease, may play a role in the pathogenesis of essential hypertension. The mechanism of this disease has not been elucidated, but it may be related to impairment of vascular endothelial and smooth muscle cell function. Therefore, the occurrence of endothelial dysfunction could contribute to alterations of the endothelium-dependent vasomotor regulation. Elevated homocysteinemia diminishes the vasodilation by nitric oxide, increases oxidative stress, stimulates the proliferation of vascular smooth muscle cells, and alters the elastic properties of the vascular wall. Thus, homocysteine contributes to elevate the blood pressure. Also it is known that elevated plasma levels of homocysteine could lead to oxidant injury to the endothelium. The correction of elevated homocysteinemia by administration of vitamins B12 and B6 plus folic acid, could be a useful adjuvant therapy of hypertension. However, further controlled randomized trials are necessary to establish the efficacy and tolerability of these potentially therapeutic agents. PMID:14615465

  13. The A2B adenosine receptor modulates pulmonary hypertension associated with interstitial lung disease

    PubMed Central

    Karmouty-Quintana, Harry; Zhong, Hongyan; Acero, Luis; Weng, Tingting; Melicoff, Ernestina; West, James D.; Hemnes, Anna; Grenz, Almut; Eltzschig, Holger K.; Blackwell, Timothy S.; Xia, Yang; Johnston, Richard A.; Zeng, Dewan; Belardinelli, Luiz; Blackburn, Michael R.

    2012-01-01

    Development of pulmonary hypertension is a common and deadly complication of interstitial lung disease. Little is known regarding the cellular and molecular mechanisms that lead to pulmonary hypertension in patients with interstitial lung disease, and effective treatment options are lacking. The purpose of this study was to examine the adenosine 2B receptor (A2BR) as a regulator of vascular remodeling and pulmonary hypertension secondary to pulmonary fibrosis. To accomplish this, cellular and molecular changes in vascular remodeling were monitored in mice exposed to bleomycin in conjunction with genetic removal of the A2BR or treatment with the A2BR antagonist GS-6201. Results demonstrated that GS-6201 treatment or genetic removal of the A2BR attenuated vascular remodeling and hypertension in our model. Furthermore, direct A2BR activation on vascular cells promoted interleukin-6 and endothelin-1 release. These studies identify a novel mechanism of disease progression to pulmonary hypertension and support the development of A2BR antagonists for the treatment of pulmonary hypertension secondary to interstitial lung disease.—Karmouty-Quintana, H., Zhong, H., Acero, L., Weng, T., Melicoff, E., West, J. D., Hemnes, A., Grenz, A., Eltzschig, H. K., Blackwell, T. S., Xia, Y., Johnston, R. A., Zeng, D., Belardinelli, L., Blackburn, M. R. The A2B adenosine receptor modulates pulmonary hypertension associated with interstitial lung disease. PMID:22415303

  14. Radiofrequency attenuator and method

    DOEpatents

    Warner, Benjamin P.; McCleskey, T. Mark; Burrell, Anthony K.; Agrawal, Anoop; Hall, Simon B.

    2009-01-20

    Radiofrequency attenuator and method. The attenuator includes a pair of transparent windows. A chamber between the windows is filled with molten salt. Preferred molten salts include quarternary ammonium cations and fluorine-containing anions such as tetrafluoroborate (BF.sub.4.sup.-), hexafluorophosphate (PF.sub.6.sup.-), hexafluoroarsenate (AsF.sub.6.sup.-), trifluoromethylsulfonate (CF.sub.3SO.sub.3.sup.-), bis(trifluoromethylsulfonyl)imide ((CF.sub.3SO.sub.2).sub.2N.sup.-), bis(perfluoroethylsulfonyl)imide ((CF.sub.3CF.sub.2SO.sub.2).sub.2N.sup.-) and tris(trifluoromethylsulfonyl)methide ((CF.sub.3SO.sub.2).sub.3C.sup.-). Radicals or radical cations may be added to or electrochemically generated in the molten salt to enhance the RF attenuation.

  15. Radiofrequency attenuator and method

    DOEpatents

    Warner, Benjamin P.; McCleskey, T. Mark; Burrell, Anthony K.; Agrawal, Anoop; Hall, Simon B.

    2009-11-10

    Radiofrequency attenuator and method. The attenuator includes a pair of transparent windows. A chamber between the windows is filled with molten salt. Preferred molten salts include quarternary ammonium cations and fluorine-containing anions such as tetrafluoroborate (BF.sub.4.sup.-), hexafluorophosphate (PF.sub.6.sup.-), hexafluoroarsenate (AsF.sub.6.sup.-), trifluoromethylsulfonate (CF.sub.3SO.sub.3.sup.-), bis(trifluoromethylsulfonyl)imide ((CF.sub.3SO.sub.2).sub.2N.sup.-), bis(perfluoroethylsulfonyl)imide ((CF.sub.3CF.sub.2SO.sub.2).sub.2N.sup.-) and tris(trifluoromethylsulfonyl)methide ((CF.sub.3SO.sub.2).sub.3 C.sup.-). Radicals or radical cations may be added to or electrochemically generated in the molten salt to enhance the RF attenuation.

  16. Seismic attenuation in Florida

    SciTech Connect

    Bellini, J.J.; Bartolini, T.J.; Lord, K.M.; Smith, D.L. . Dept. of Geology)

    1993-03-01

    Seismic signals recorded by the expanded distribution of earthquake seismograph stations throughout Florida and data from a comprehensive review of record archives from stations GAI contribute to an initial seismic attenuation model for the Florida Plateau. Based on calculations of surface particle velocity, a pattern of attenuation exists that appears to deviate from that established for the remainder of the southeastern US. Most values suggest greater seismic attenuation within the Florida Plateau. However, a separate pattern may exist for those signals arising from the Gulf of Mexico. These results have important implications for seismic hazard assessments in Florida and may be indicative of the unique lithospheric identity of the Florida basement as an exotic terrane.

  17. Region-specific changes in sympathetic nerve activity in angiotensin II-salt hypertension in the rat.

    PubMed

    Osborn, John W; Fink, Gregory D

    2010-01-01

    It is now well accepted that many forms of experimental hypertension and human essential hypertension are caused by increased activity of the sympathetic nervous system. However, the role of region-specific changes in sympathetic nerve activity (SNA) in the pathogenesis of hypertension has been difficult to determine because methods for chronic measurement of SNA in conscious animals have not been available. We have recently combined indirect, and continuous and chronic direct, assessment of region-specific SNA to characterize hypertension produced by administration of angiotensin II (Ang II) to rats consuming a high-salt diet (Ang II-salt hypertension). Angiotensin II increases whole-body noradrenaline (NA) spillover and depressor responses to ganglionic blockade in rats consuming a high-salt diet, but not in rats on a normal-salt diet. Despite this evidence for increased 'whole-body SNA' in Ang II-salt hypertensive rats, renal SNA is decreased in this model and renal denervation does not attenuate the steady-state level of arterial pressure. In addition, neither lumbar SNA, which largely targets skeletal muscle, nor hindlimb NA spillover is changed from control levels in Ang II-salt hypertensive rats. However, surgical denervation of the splanchnic vascular bed attenuates/abolishes the increase in arterial pressure and total peripheral resistance, as well as the decrease in vascular capacitance, observed in Ang II-salt hypertensive rats. We hypothesize that the 'sympathetic signature' of Ang II-salt hypertension is characterized by increased splanchnic SNA, no change in skeletal muscle SNA and decreased renal SNA, and this sympathetic signature creates unique haemodynamic changes capable of producing sustained hypertension. PMID:19717492

  18. Weight control in the management of hypertension. World Hypertension League.

    PubMed Central

    1989-01-01

    This article, which includes a brief description of the mechanisms and some epidemiological findings in obesity and high blood pressure, sums up present knowledge on a complex subject and provides guidance to medical practitioners on the management of obese hypertensive patients. Weight reduction, together with drug therapy in severe and moderate hypertension, and other non-pharmacological methods and continuing observation in mild hypertension are the essential measures to be applied. In addition to the lowering of blood pressure, weight loss offers several other metabolic and haemodynamic benefits. PMID:2670295

  19. Impact of obesity on renal structure and function in the presence and absence of hypertension: evidence from melanocortin-4 receptor-deficient mice.

    PubMed

    do Carmo, Jussara M; Tallam, Lakshmi S; Roberts, John V; Brandon, Elizabeth L; Biglane, John; da Silva, Alexandre A; Hall, John E

    2009-09-01

    The purpose of this study was to determine the long-term impact of obesity and related metabolic abnormalities in the absence and presence of hypertension on renal injury and salt-sensitivity of blood pressure. Markers of renal injury and blood pressure salt sensitivity were assessed in 52- to 55-wk-old normotensive melanocortin-4 receptor-deficient (MC4R-/-) mice and lean C57BL/6J wild-type (WT) mice and in 22-wk-old MC4R-/- and WT mice made hypertensive by N(G)-nitro-L-arginine methyl ester (L-NAME) in the drinking water for 8 wk. Old MC4R-/- mice were 60% heavier, hyperinsulinemic, and hyperleptinemic but had similar mean arterial pressure (MAP) as WT mice (115 +/- 2 and 117 +/- 2 mmHg) on normal salt diet (0.4% NaCl). A high-salt diet (4.0% NaCl) for 12 days did not raise MAP in obese or lean mice [DeltaMAP: MC4R (-/-) 4 +/- 2 mmHg; WT, 2 +/- 1 mmHg]. Obese MC4R-/- mice had 23% greater glomerular tuft area and moderately increased GFR compared with WT mice. Bowman's space, total glomerular area, mesangial matrix, urinary albumin excretion (UAE), renal TGF-beta and collagen expression were not significantly different between old MC4R-/- and WT mice. Renal lipid content was greater but renal macrophage count was markedly lower in MC4R-/- than WT mice. Mild increases in MAP during L-NAME treatment (approximately 16 mmHg) caused small, but greater, elevations in UAE, renal TGF-beta content, and macrophage infiltration in MC4R-/- compared with WT mice without significant changes in glomerular structure. Thus despite long-term obesity and multiple metabolic abnormalities, MC4R-/- mice have no evidence of renal injury or salt-sensitivity of blood pressure. These observations suggest that elevations in blood pressure may be necessary for obesity and related metabolic abnormalities to cause major renal injury or that MC4R-/- mice are protected from renal injury by mechanisms that are still unclear. PMID:19605765

  20. Hypertension in Patients with Cancer

    PubMed Central

    de Souza, Vinicius Barbosa; Silva, Eduardo Nani; Ribeiro, Mario Luiz; Martins, Wolney de Andrade

    2015-01-01

    There is a known association between chemotherapy and radiotherapy for treatment of cancer patients and development or worsening of hypertension. The aim of this article is to review this association. A literature search was conducted for articles reporting this association on the databases PubMed, SciELO and LILACS between 1993 and 2013. There was a high coprevalence of hypertension and cancer, since both diseases share the same risk factors, such as sedentary lifestyle, obesity, smoking, unhealthy diet and alcohol abuse. The use of chemotherapy and adjuvant drugs effective in the treatment of cancer increased the survival rate of these patients and, consequently, increased the incidence of hypertension. We described the association between the use of angiogenesis inhibitors (bevacizumab, sorafenib and sunitinib), corticosteroids, erythropoietin and non-steroidal anti-inflammatory drugs with the development of hypertension. We also described the relationship between hypertension and carotid baroreceptor injury secondary to cervical radiotherapy. Morbidity and mortality increased in patients with cancer and hypertension without proper antihypertensive treatment. We concluded that there is need for early diagnosis, effective monitoring and treatment strategies for hypertension in cancer patients in order to reduce cardiovascular morbidity and mortality. PMID:25742420

  1. Dermatoglyphics in hypertension: a review.

    PubMed

    Wijerathne, Buddhika T B; Meier, Robert J; Agampodi, Thilini C; Agampodi, Suneth B

    2015-01-01

    Hypertension is a major contributor to the global burden of disease and mortality. A major medical advancement would be a better means to ascertain which persons are at higher risk for becoming hypertensive beforehand. To that end, there have been a number of studies showing that certain dermatoglyphic markers are associated with hypertension. This association could be explained if the risk toward developing hypertension later on in life is somehow connected with fetal development of dermatoglyphics. It would be highly valuable from a clinical standpoint if this conjecture could be substantiated since dermatoglyphic markers could then be used for screening out individuals who might be at an elevated risk of becoming hypertensive. The aim of this review was to search for and appraise available studies that pertain to the association between hypertension and dermatoglyphics.A systematic literature search conducted using articles from MEDLINE (PubMed), Trip, Cochran, Google scholar, and gray literature until December 2014. Of the 37 relevant publications, 17 were included in the review. The review performed according to the preferred reporting items for systematic reviews and meta-analyses (PRISMA) statement.This review showed a fairly consistent finding of an increased frequency of whorl patterns along with a higher mean total ridge count in digital dermatoglyphic results in hypertensive samples compared to controls. However, it was imperative to discuss several limitations found in the studies that could make this association as yet unsettled. PMID:26265377

  2. Pulmonary arterial hypertension

    PubMed Central

    2013-01-01

    Pulmonary arterial hypertension (PAH) is a chronic and progressive disease leading to right heart failure and ultimately death if untreated. The first classification of PH was proposed in 1973. In 2008, the fourth World Symposium on PH held in Dana Point (California, USA) revised previous classifications. Currently, PH is devided into five subgroups. Group 1 includes patients suffering from idiopathic or familial PAH with or without germline mutations. Patients with a diagnosis of PAH should systematically been screened regarding to underlying mutations of BMPR2 gene (bone morphogenetic protein receptor type 2) or more rarely of ACVRL1 (activine receptor-like kinase type 1), ENG (endogline) or Smad8 genes. Pulmonary veno occusive disease and pulmonary capillary hemagiomatosis are individualized and designated as clinical group 1'. Group 2 'Pulmonary hypertension due to left heart diseases' is divided into three sub-groups: systolic dysfonction, diastolic dysfonction and valvular dysfonction. Group 3 'Pulmonary hypertension due to respiratory diseases' includes a heterogenous subgroup of respiratory diseases like PH due to pulmonary fibrosis, COPD, lung emphysema or interstitial lung disease for exemple. Group 4 includes chronic thromboembolic pulmonary hypertension without any distinction of proximal or distal forms. Group 5 regroup PH patients with unclear multifactorial mechanisms. Invasive hemodynamic assessment with right heart catheterization is requested to confirm the definite diagnosis of PH showing a resting mean pulmonary artery pressure (mPAP) of ≥ 25 mmHg and a normal pulmonary capillary wedge pressure (PCWP) of ≤ 15 mmHg. The assessment of PCWP may allow the distinction between pre-capillary and post-capillary PH (PCWP > 15 mmHg). Echocardiography is an important tool in the management of patients with underlying suspicion of PH. The European Society of Cardiology and the European Respiratory Society (ESC-ERS) guidelines specify its role

  3. Pulmonary arterial hypertension.

    PubMed

    Montani, David; Günther, Sven; Dorfmüller, Peter; Perros, Frédéric; Girerd, Barbara; Garcia, Gilles; Jaïs, Xavier; Savale, Laurent; Artaud-Macari, Elise; Price, Laura C; Humbert, Marc; Simonneau, Gérald; Sitbon, Olivier

    2013-01-01

    Pulmonary arterial hypertension (PAH) is a chronic and progressive disease leading to right heart failure and ultimately death if untreated. The first classification of PH was proposed in 1973. In 2008, the fourth World Symposium on PH held in Dana Point (California, USA) revised previous classifications. Currently, PH is devided into five subgroups. Group 1 includes patients suffering from idiopathic or familial PAH with or without germline mutations. Patients with a diagnosis of PAH should systematically been screened regarding to underlying mutations of BMPR2 gene (bone morphogenetic protein receptor type 2) or more rarely of ACVRL1 (activine receptor-like kinase type 1), ENG (endogline) or Smad8 genes. Pulmonary veno occusive disease and pulmonary capillary hemagiomatosis are individualized and designated as clinical group 1'. Group 2 'Pulmonary hypertension due to left heart diseases' is divided into three sub-groups: systolic dysfonction, diastolic dysfonction and valvular dysfonction. Group 3 'Pulmonary hypertension due to respiratory diseases' includes a heterogenous subgroup of respiratory diseases like PH due to pulmonary fibrosis, COPD, lung emphysema or interstitial lung disease for exemple. Group 4 includes chronic thromboembolic pulmonary hypertension without any distinction of proximal or distal forms. Group 5 regroup PH patients with unclear multifactorial mechanisms. Invasive hemodynamic assessment with right heart catheterization is requested to confirm the definite diagnosis of PH showing a resting mean pulmonary artery pressure (mPAP) of ≥ 25 mmHg and a normal pulmonary capillary wedge pressure (PCWP) of ≤ 15 mmHg. The assessment of PCWP may allow the distinction between pre-capillary and post-capillary PH (PCWP > 15 mmHg). Echocardiography is an important tool in the management of patients with underlying suspicion of PH. The European Society of Cardiology and the European Respiratory Society (ESC-ERS) guidelines specify its role

  4. In the clinic: hypertension.

    PubMed

    Weir, Matthew R

    2014-12-01

    This issue provides a clinical overview of Hypertension focusing on prevention, diagnosis, treatment, practice improvement, and patient information. The content of In the Clinic is drawn from the clinical information and education resources of the American College of Physicians (ACP), including ACP Smart Medicine and MKSAP (Medical Knowledge and Self-Assessment Program). Annals of Internal Medicine editors develop In the Clinic from these primary sources in collaboration with the ACP's Medical Education and Publishing divisions and with the assistance of science writers and physician writers. Editorial consultants from ACP Smart Medicine and MKSAP provide expert review of the content. Readers who are interested in these primary resources for more detail can consult http://smartmedicine.acponline.org, http://mksap.acponline.org, and other resources referenced in each issue of In the Clinic. PMID:25437425

  5. Treatment of pulmonary hypertension

    PubMed Central

    Patel, Rajendrakumar; Aronow, Wilbert S.; Patel, Laxeshkumar; Gandhi, Kaushang; Desai, Harit; Kaul, Dhiraj; Sahgal, Sumir P.

    2012-01-01

    Summary Pulmonary arterial hypertension (PAH) is a chronic progressive disease of the pulmonary vasculature characterized by elevated pulmonary arterial pressure and secondary right ventricular failure. PAH is considered a life-threatening condition unless treated. This article provides a comprehensive review of controlled and uncontrolled trials to define the risk-benefit for different therapeutic options of this clinical disorder. Relevant published articles were identified through searches of the National Center for Biotechnology PubMed database. All therapeutic measures for PAH were discussed. Six drugs have been approved in the United States for the treatment of PAH. Extensive medical advancement has been achieved in treatment of PAH. However, none of the approved therapies have shown ability to cure the disease. New research should be performed to develop promising new therapies. PMID:22460104

  6. Paraventricular Nucleus Infusion of Epigallocatechin-3-O-Gallate Improves Renovascular Hypertension.

    PubMed

    Yi, Qiu-Yue; Qi, Jie; Yu, Xiao-Jing; Li, Hong-Bao; Zhang, Yan; Su, Qing; Shi, Tao; Zhang, Dong-Mei; Guo, Jing; Feng, Zhi-Peng; Wang, Mo-Lin; Zhu, Guo-Qing; Liu, Jin-Jun; Shi, Xiao-Lian; Kang, Yu-Ming

    2016-07-01

    Oxidative stress plays an important role in the pathogenesis of hypertension. Epigallocatechin-3-O-gallate (EGCG) is the main polyphenol present in green tea and is known for its potent antioxidant and anti-inflammatory properties. In the present study, we hypothesize that EGCG attenuates oxidative stress in the paraventricular nucleus of hypothalamus (PVN), thereby decreasing the blood pressure and sympathetic activity in renovascular hypertensive rats. After renovascular hypertension was induced in male Sprague-Dawley rats by the two-kidney one-clip (2K-1C) method, the rats received bilateral PVN infusion of EGCG (20 μg/h) or vehicle via osmotic minipump for 4 weeks. Our results were shown as follows: (1) Hypertension induced by 2K-1C was associated with the production of reactive oxygen species in the PVN; (2) chronic infusion of EGCG in the PVN decreased stress-related NAD(P)H oxidase subunit gp91(phox) and NOX-4 and increased the activity of antioxidant enzymes (SOD-1), also balanced the content of cytokines (IL-1β, IL-6, IL-10 and MCP-1) in the PVN, and attenuated the level of norepinephrine in plasma of 2K-1C rats. Our findings provide strong evidence that PVN infusion of EGCG inhibited renovascular hypertension progression through its potent anti-oxidative and anti-inflammatory activity in the PVN. PMID:26162770

  7. Tritium Attenuation by Distillation

    SciTech Connect

    Wittman, N.E.

    2001-07-31

    The objective of this study was to determine how a 100 Area distillation system could be used to reduce to a satisfactory low value the tritium content of the dilute moderator produced in the 100 Area stills, and whether such a tritium attenuator would have sufficient capacity to process all this material before it is sent to the 400 Area for reprocessing.

  8. Sick But Unaware: Hypertension in Indonesia.

    PubMed

    Sohn, Kitae

    2015-01-01

    Discrepancies between self-reported and measured hypertension pose a great risk to health because they prevent timely treatment. Analyzing the Indonesian Family Life Survey, we compared self-reported and measured hypertension to assess the extent of the misclassification of hypertension. Building on this, we estimated factors related to self-reported and measured hypertension. Our results show that different factors were involved in each case, suggesting that they are two different phenomena. More importantly, we estimated factors that increased awareness of hypertension and found that visiting a health facility was a very effective way of increasing awareness of hypertension among hypertensive patients. PMID:26652684

  9. Hyperuricemia, Cardiovascular Disease, and Hypertension

    PubMed Central

    Kuwabara, Masanari

    2016-01-01

    In recent years, there has been an increase in the prevalence of hyperuricemia, and the latter has attracted attention as an adult lifestyle-associated disease, together with hypertension, diabetes, and dyslipidemia. Although hyperuricemia is known to be an independent risk factor for hypertension, whether it is an independent risk factor for cardiovascular disease remains controversial. Recently, some small-scale interventional studies on antihyperuricemic medications showed that the latter improved angina symptoms and prevented cardiovascular disease. Here, we will mainly explain the cause of hyperuricemia and the associations between hyperuricemia, hypertension, and cardiovascular disease based on the latest published evidence. PMID:27195245

  10. Collateral Pathways in Portal Hypertension

    PubMed Central

    Sharma, Malay; Rameshbabu, Chittapuram S.

    2012-01-01

    Presence of portosystemic collateral veins (PSCV) is common in portal hypertension due to cirrhosis. Physiologically, normal portosystemic anastomoses exist which exhibit hepatofugal flow. With the development of portal hypertension, transmission of backpressure leads to increased flow in these patent normal portosystemic anastomoses. In extrahepatic portal vein obstruction collateral circulation develops in a hepatopetal direction and portoportal pathways are frequently found. The objective of this review is to illustrate the various PSCV and portoportal collateral vein pathways pertinent to portal hypertension in liver cirrhosis and EHPVO. PMID:25755456

  11. Precursors of Hypertension: A Review

    PubMed Central

    Thomas, John; Neser, William B.; Thomas, Johniene; Semenya, Kofi; Green, Donald R.

    1983-01-01

    Recent advances in hypertension therapy have been remarkable; however, much less is known about those precursors that facilitate preventive and early intervention measures. This review of the literature indicates that relevant precursors are early elevated casual systolic blood pressures, positive family history, and obesity in females. Additional predisposing or enhancing factors point to high sodium ingestion, heavy smoking, and high socioecologic stress. Evidence for a high-risk hypertensive personality is not conclusive. There is a paucity of longitudinal data on hypertension in the black population. PMID:6864814

  12. Alkaloids of Nitraria sibirica Pall. decrease hypertension and albuminuria in angiotensin II-salt hypertension.

    PubMed

    Bakri, Mahinur; Yi, Yang; Chen, Ling-Dan; Aisa, Haji Akber; Wang, Mong-Heng

    2014-04-01

    In traditional Chinese medicine, Nitraria sibirica Pall. (Nitrariaceae) is used to treat hypertension. This study determined the effects of the total alkaloids of the leaves of Nitraria sibirica (NSTA) on blood pressure and albuminuria in mice treated with angiotensin II and a high-salt diet (ANG/HS). Adult mice were divided into three groups: control; infused with angiotensin II and fed a diet containing 4% NaCl (ANG/HS; and ANG/HS plus injection of NSTA (1 mg·kg(-1)·d(-1), i.p.). After treatment of these regimens, daily water and food intake, kidney weight, blood pressure, urinary albumin excretion, renal concentrations of inflammatory markers, including soluble intercellular adhesion molecule-1 (sICAM-1) and monocyte chemoattractant protein-1 (MCP-1), and the expression of renal fibrosis markers were determined. Compared to the control group, the ANG/HS group had higher blood pressure and urinary albumin excretion. Treatment with NSTA in ANG/HS mice for three weeks significantly reduced blood pressure and urinary albumin excretion. ANG/HS treatment caused elevated levels of sICAM-1 and MCP-1, as well as increased fibrosis markers. Concurrent treatment with ANG/HS and NSTA attenuated the levels and expression of renal inflammatory and fibrosis markers. Treatment with NSTA effectively reduces hypertension-induced albuminuria through the reduction of renal inflammatory and fibrosis markers. PMID:24863351

  13. Four faces of baroreflex failure: hypertensive crisis, volatile hypertension, orthostatic tachycardia, and malignant vagotonia

    NASA Technical Reports Server (NTRS)

    Ketch, Terry; Biaggioni, Italo; Robertson, RoseMarie; Robertson, David

    2002-01-01

    BACKGROUND: The baroreflex normally serves to buffer blood pressure against excessive rise or fall. Baroreflex failure occurs when afferent baroreceptive nerves or their central connections become impaired. In baroreflex failure, there is loss of buffering ability, and wide excursions of pressure and heart rate occur. Such excursions may derive from endogenous factors such as stress or drowsiness, which result in quite high and quite low pressures, respectively. They may also derive from exogenous factors such as drugs or environmental influences. METHODS AND RESULTS: Impairment of the baroreflex may produce an unusually broad spectrum of clinical presentations; with acute baroreflex failure, a hypertensive crisis is the most common presentation. Over succeeding days to weeks, or in the absence of an acute event, volatile hypertension with periods of hypotension occurs and may continue for many years, usually with some attenuation of pressor surges and greater prominence of depressor valleys during long-term follow-up. With incomplete loss of baroreflex afferents, a mild syndrome of orthostatic tachycardia or orthostatic intolerance may appear. Finally, if the baroreflex failure occurs without concomitant destruction of the parasympathetic efferent vagal fibers, a resting state may lead to malignant vagotonia with severe bradycardia and hypotension and episodes of sinus arrest. CONCLUSIONS: Although baroreflex failure is not the most common cause of the above conditions, correct differentiation from other cardiovascular disorders is important, because therapy of baroreflex failure requires specific strategies, which may lead to successful control.

  14. Dietary calcium and magnesium in the development of hypertension in the spontaneously hypertensive rat

    SciTech Connect

    Evans, G.; Weaver, C.M.; Harrington, D.D.; Babbs, C.F.

    1986-03-01

    The role of dietary calcium and magnesium in attenuation of hypertension was studied in 9 groups of 9 spontaneously hypertensive rats ages 8 to 31 weeks. The animals were fed AIN 76 semipurified diets altered in calcium (0.075%, 0.5%, and 2.5%) and magnesium (0.01%, 0.05%, and 0.75%) using a 3 x 3 factorial design. An inverse relationship between dietary calcium and systolic blood pressure as determined by the photoelectric tail cuff method became significant (p<0.05) after 12 weeks. Repeated measures analysis of variance indicated that dietary magnesium had no effect on systolic blood pressure; no calcium x magnesium interaction was observed. Total and ultrafiltrable serum calcium had a significant inverse correlation with blood pressure (-0.4642, p = .001 and -0.5568, p = .001 respectively). Total and ultrafiltrable serum magnesium reflected dietary magnesium concentration. Magnesium deficiency signs, deposition of calcium in kidneys, and histological lesions were observed in high calcium fed groups receiving normal and low levels of magnesium. Thus, a lowering of blood pressure by calcium supplementation without concomitant magnesium supplementation was accompanied by biochemical and histologic abnormalities in this animal model.

  15. Structural and Functional Vascular Alterations and Incident Hypertension in Normotensive Adults

    PubMed Central

    Peralta, Carmen A.; Adeney, Kathryn L.; Shlipak, Michael G.; Jacobs, David; Duprez, Daniel; Bluemke, David; Polak, Joseph; Psaty, Bruce; Kestenbaum, Bryan R.

    2010-01-01

    Vascular abnormalities may exist before clinical hypertension. Using Poisson regression, the authors studied the association of coronary artery calcium (CAC), common carotid intima-media thickness (CIMT), aortic distensibility, and large and small arterial elasticity with incident hypertension among 2,512 normotensive US adults free of cardiovascular disease. Incidence rate ratios for incident hypertension (blood pressure ≥140/90 mm Hg or new antihypertensive medication) were calculated. Increased CAC was associated with incident hypertension in demographics-adjusted models (incidence rate ratio (IRR) = 1.35, 95% confidence interval (CI): 1.04, 1.75; IRR = 1.35, 95% CI: 1.02, 1.78; and IRR = 1.59, 95% CI: 1.12, 2.25 for CAC scores of 30–99, 100–399, and ≥400, respectively) but was attenuated after further adjustment. Increased common CIMT was associated with incident hypertension (IRR = 1.77, 95% CI: 1.28, 2.46 for quintile 4; IRR = 1.80, 95% CI: 1.28, 2.53 for quintile 5). Participants with the lowest, compared with the highest, aortic distensibility had an increased risk of hypertension (IRR = 1.75, 95% CI: 1.10, 2.79), as did those with the lowest large arterial elasticity (IRR = 1.49, 95% CI: 1.11, 1.99). Lower small arterial elasticity was incrementally associated with incident hypertension starting at quintile 2 (IRR = 2.01, 95% CI: 1.39, 2.91; IRR = 2.47, 95% CI: 1.71, 3.57; IRR = 2.73, 95% CI: 1.88, 3.95; and IRR = 2.85, 95% CI: 1.95, 4.16). Structural and functional vascular abnormalities are independent predictors of incident hypertension. These findings are important for understanding the pathogenesis of hypertension. PMID:19951938

  16. Effect of 2 different anesthesia methods on stress response in neurosurgical patients with hypertension or normal

    PubMed Central

    Chen, Ying; Jiang, Shan; Wu, Yong

    2016-01-01

    Abstract Hypertensive patients in neurosurgery are becoming more common, which increased the risk of surgical stress response. Meanwhile, the relationship between hypertension and anesthesia methods is unclear on the stress response. The purpose of this study is to compare the effect of different anesthesia methods on high-sensitivity C-reactive protein (Hs-CRP), blood glucose, and leucocyte levels in neurosurgical patients with hypertension or normal. Eighty neurosurgical patients were randomly divided into 4 groups (n = 20): balanced anesthesia group (A), balanced anesthesia with hypertension group (B), total intravenous anesthesia group (C), total intravenous anesthesia with hypertension group (D). The levels of Hs-CRP, blood glucose, leucocyte count, and neutrophil percentage and were detected at before anesthesia (T0), during anesthesia (T1), 2 hours post anesthesia (T2), 24 hours post anesthesia (T3). Patients with hypertension had higher Hs-CRP expression, blood glucose, and neutrophil percentage at time T0 than those of normal, but not leucocyte count. At time T3, patients with hypertension in D group had lower Hs-CRP expression than those in B group (P < 0.01). Patients with normal in C group had lower Hs-CRP expression (P < 0.01), blood glucose (P < 0.05), and leukocyte count (P < 0.05) than those in A group. Both hypertension history and anesthesia method had significant effects on the Hs-CRP expression, blood glucose, and leukocyte count. Total intravenous anesthesia decreases Hs-CRP expressions more efficiently than balanced anesthesia in neurosurgical patients with hypertension or normal. Moreover, total intravenous anesthesia can availably reduce the perioperative stress response by attenuating the increase of blood glucose and leukocyte count in normal tensive patients. PMID:27583931

  17. A compact rotary vane attenuator

    NASA Technical Reports Server (NTRS)

    Nixon, D. L.; Otosh, T. Y.; Stelzried, C. T.

    1969-01-01

    Rotary vane attenuator, when used as a front end attenuator, introduces an insertion loss that is proportional to the angle of rotation. New technique allows the construction of a shortened compact unit suitable for most installations.

  18. Sex differences in primary hypertension

    PubMed Central

    2012-01-01

    Men have higher blood pressure than women through much of life regardless of race and ethnicity. This is a robust and highly conserved sex difference that it is also observed across species including dogs, rats, mice and chickens and it is found in induced, genetic and transgenic animal models of hypertension. Not only do the differences between the ovarian and testicular hormonal milieu contribute to this sexual dimorphism in blood pressure, the sex chromosomes also play a role in and of themselves. This review primarily focuses on epidemiological studies of blood pressure in men and women and experimental models of hypertension in both sexes. Gaps in current knowledge regarding what underlie male-female differences in blood pressure control are discussed. Elucidating the mechanisms underlying sex differences in hypertension may lead to the development of anti-hypertensives tailored to one's sex and ultimately to improved therapeutic strategies for treating this disease and preventing its devastating consequences. PMID:22417477

  19. Intracranial Hypertension: Medication and Surgery

    MedlinePlus

    ... http://www.ihrfoundation.org/hypertension/info/C172 Surgery Optic Nerve Fenestration When sight is at risk and drug therapy has been unsuccessful, an optic nerve fenestration (also called an optic nerve sheath ...

  20. [Personality characteristics of hypertensive patients].

    PubMed

    Kubej, P; Korán, M

    1989-02-01

    Essential hypertension, as well-known specialists believe, is due both to genetic and external environment factors. Apart from the steadily growing complexity of social life and various important life events, high-risk factors may also be seen in a certain way of behaviour and man's psychophysiological reactivity. Recent literature on this topic informs about some common characteristics found in the behaviour of hypertensive persons, for example: anxiety in social contacts, suppressed hostility, manifestations of perfectionism, suppression of emotions, exaggerated behavioral adaptability and defensive attitudes to stress stimuli. In accordance with literary data, the control group of hypertensive patients (N = 89) gave evidence of some identical characteristics. Their knowledge permits to carry out more specific attempts at influencing hypertension in a non-pharmacological way. PMID:2720750

  1. Controversies Among the Hypertension Guidelines.

    PubMed

    Ripley, Toni L; Baumert, Mary

    2016-02-01

    Hypertension affects 80 million people in the United States. It remains poorly controlled, with only 54% of diagnosed patients treated to blood pressure targets. Hypertension management is complex in part due to the volume of antihypertensive agents, variable patient needs and responses, and inconsistent design and outcomes from clinical trials. Therefore, trustworthy clinical practice guidelines have a key role in hypertension management. The United States experienced a 10-year gap in publication of hypertension guidelines, followed by multiple guideline publications in 2013. These guidelines led to more controversy than clarity, as there was discordance among them. This review summarizes the guidelines and clinical statements influencing the current debate in order to facilitate appropriate application. PMID:26668216

  2. A case of hypertensive urgency.

    PubMed

    Baum, Laurence

    2016-08-01

    A 41-year-old male Nepalese soldier presented to the primary care medical centre with a 1-week history of fatigue and muscle aches following a trip to Nepal. His BP was 164/98 but was otherwise normal. Four days later he presented with new symptoms of sweating and palpitations and a BP of 200/127 whereupon he was admitted to hospital with the diagnosis of hypertensive crisis. Appropriate investigation and initial management were undertaken, and he was discharged after 12 h on antihypertensive treatment. This case highlights the risk of hypertensive crisis in both diagnosed and silent hypertensive disease, and the review highlights the presentations, initial investigation and different management of hypertensive crisis. PMID:26002343

  3. Systemic hypertension and its management.

    PubMed

    Henik, R A

    1997-11-01

    The pathophysiology of hypertension in dogs and cats, the methods available to monitor blood pressure, and the signs and treatment of hypertension are reviewed. Clinical signs of hypertension are usually referable to target organ damage, most notably in ophthalmic, renal, and cardiovascular tissues, which have a rich arteriolar supply. Blood pressure should be measured in any animal with renal disease, hyperthyroidism, hyperadrenocorticism, retinal detachment or hemorrhage, hyphema, or echocardiographically determined cardiac hypertrophy. All cats with acquired cardiac murmur should also be evaluated for hypertension. Antihypertensive medication should be administered if the indirect blood pressure in cats is consistently over 170/100 mmHg, or if the indirect blood pressure in dogs is greater than 180/100 mmHg. PMID:9348634

  4. [Resistant hypertension : What is it?].

    PubMed

    Luft, F C

    2015-03-01

    When blood pressure is poorly controlled despite treatment with a diuretic and two antihypertensive drugs at adequate doses, the hypertension is termed resistant. The prevalence of resistant hypertension is increasing. Once pseudo-resistance due to poor compliance, secondary forms of hypertension, and massive salt consumption have been excluded, some authorities maintain that blood pressure can be invariably lowered using minoxidil or mineralocorticoid receptor blockade. I also adhered to this belief until we encountered a patient who despite treatment with seven antihypertensive agents, electrical carotid sinus stimulation, and catheter-based renal denervation continued to exhibit extraordinarily high blood pressure values. I am now convinced that resistant hypertension does indeed exist. The prevalence of such patients can be substantially reduced by means of a thorough history and physical examination, determining drug serum concentrations, and excluding secondary causes. PMID:25668441

  5. A Practical Approach to Hypertension

    PubMed Central

    Dodek, Arthur; Wilkins, Graeme

    1976-01-01

    At least ten percent of the adult population has hypertension. Detection and effective treatment of hypertension are imperative in order to prevent the cardiovascular consequences. Effective antihypertensive treatment reduces morbidity and mortality. Weight reduction and sodium restriction are important fundamentals, and diuretics are the cornerstone of drug therapy. In order to increase patient compliance, treatment should be simple and drugs given twice daily wherever possible. PMID:20469276

  6. Hypertension in the emergency department.

    PubMed

    Jackson, R E

    1988-05-01

    Hypertensive emergencies are now rare and are recognized by the deleterious effect on end-organs. Prompt, efficacious treatment is critical, and the current drug of choice for most episodes is sodium nitroprusside. Hypertensive urgencies are more common than are emergencies, and are distinguished by diastolic pressures greater than 115 mm Hg without end-organ dysfunction. Although there are many efficacious agents, one excellent choice is nifedipine. PMID:3280299

  7. ALLOPURINOL DOES NOT DECREASE BLOOD PRESSURE OR PREVENT THE DEVELOPMENT OF HYPERTENSION IN THE DOCA-SALT RAT MODEL

    PubMed Central

    Szasz, Theodora; Linder, A. Elizabeth; Davis, Robert P.; Burnett, Robert; Fink, Gregory D.; Watts, Stephanie W.

    2010-01-01

    Reactive oxygen species (ROS) play an important role in the pathogenesis of hypertension, disease in which ROS levels and markers of oxidative stress are increased. Xanthine oxidase (XO) is a ROS-producing enzyme the activity of which may increase during hypertension. Studies on XO inhibition effects on BP have yielded controversial results. We hypothesized that XO inhibition would decrease BP or attenuate the development of DOCA-salt hypertension. We administered the XO inhibitor, allopurinol (50 mg/kg/day, orally) or its vehicle to rats during the established or development stages of DOCA-salt hypertension. We validated XO inhibition by HPLC measurements of XO metabolites in urine, serum and tissues demonstrating decrease in products, increase in substrates and detection of the active metabolite of allopurinol, oxypurinol. We monitored BP continuously via radiotelemetry and performed gross evaluations of target organs of hypertension. Allopurinol treatment did not impact the course of DOCA-salt hypertension, regardless of the timing of administration. Aside from a significant decrease in pulse pressure in allopurinol-treated rats, no positive differences were observed between the allopurinol and the vehicle-treated rats. We conclude that XO does not play an important role in the development or maintenance of hypertension in the rat DOCA-salt hypertension model. PMID:20881613

  8. The hidden epidemic of hypertension.

    PubMed

    Grenfell, Robert; Lee, Rebecca; Stavreski, Bill; Page, Karen

    2014-04-01

    The majority of cardiovascular disease (CVD) is caused by risk factors that can be controlled, treated or modified. In terms of attributable deaths, the leading cardiovascular disease risk factor is hypertension. The Australian Health Survey results showed some startling figures-4.6 million adult Australians are hypertensive (>140/90 mmHg). Further, a fifth of the adult population experience hypertension, with more than two out of three not attaining blood pressure target levels. This is despite an estimated cost of $1 billion per annum spent on managing hypertension. It is now well recognised that the level of risk for coronary heart disease is linked to an individual's risk profile. Results indicate that many Australians have multiple risk factors, including hypertension. It could be considered that these numbers provide a proxy indicator of secondary prevention failure. Considerable attention needs to be given to the assessment of the combined risk of those with hypertension enabling effective management of identified, modifiable risk factors. We look forward to presenting the absolute risk profiles when the Australian Health Survey biometric results are released. PMID:24468162

  9. Fluid dynamic bowtie attenuators

    NASA Astrophysics Data System (ADS)

    Szczykutowicz, Timothy P.; Hermus, James

    2015-03-01

    Fluence field modulated CT allows for improvements in image quality and dose reduction. To date, only 1-D modulators have been proposed, the extension to 2-D modulation is difficult with solid-metal attenuation-based modulators. This work proposes to use liquids and gas to attenuate the x-ray beam which can be arrayed allowing for 2-D fluence modulation. The thickness of liquid and the pressure for a given path length of gas were determined that provided the same attenuation as 30 cm of soft tissue at 80, 100, 120, and 140 kV. Gaseous Xenon and liquid Iodine, Zinc Chloride, and Cerium Chloride were studied. Additionally, we performed some proof-of-concept experiments in which (1) a single cell of liquid was connected to a reservoir which allowed the liquid thickness to be modulated and (2) a 96 cell array was constructed in which the liquid thickness in each cell was adjusted manually. Liquid thickness varied as a function of kV and chemical composition, with Zinc Chloride allowing for the smallest thickness; 1.8, 2.25, 3, and 3.6 cm compensated for 30 cm of soft tissue at 80, 100, 120, and 140 kV respectively. The 96 cell Iodine attenuator allowed for a reduction in both dynamic range to the detector and scatter to primary ratio. Successful modulation of a single cell was performed at 0, 90, and 130 degrees using a simple piston/actuator. The thickness of liquids and the Xenon gas pressure seem logistically implementable within the constraints of CBCT and diagnostic CT systems.

  10. Association of Baseline Depressive Symptoms with Prevalent and Incident Pre-Hypertension and Hypertension in Postmenopausal Hispanic Women: Results from the Women’s Health Initiative

    PubMed Central

    Zambrana, Ruth E.; López, Lenny; Dinwiddie, Gniesha Y.; Ray, Roberta M.; Eaton, Charles B.; Phillips, Lawrence S.; Wassertheil-Smoller, Sylvia

    2016-01-01

    Background Depression and depressive symptoms are risk factors for hypertension (HTN) and cardiovascular disease (CVD). Hispanic women have higher rates of depressive symptoms compared to other racial/ethnic groups yet few studies have investigated its association with incident prehypertension and hypertension among postmenopausal Hispanic women. This study aims to assess if an association exists between baseline depression and incident hypertension at 3 years follow-up among postmenopausal Hispanic women. Methods Prospective cohort study, Women’s Health Initiative (WHI), included 4,680 Hispanic women who participated in the observational and clinical trial studies at baseline and at third-year follow-up. Baseline current depressive symptoms and past depression history were measured as well as important correlates of depression—social support, optimism, life events and caregiving. Multinomial logistic regression was used to estimate prevalent and incident prehypertension and hypertension in relation to depressive symptoms. Results Prevalence of current baseline depression ranged from 26% to 28% by hypertension category and education moderated these rates. In age-adjusted models, women with depression were more likely to be hypertensive (OR = 1.25; 95% CI 1.04–1.51), although results were attenuated when adjusting for covariates. Depression at baseline in normotensive Hispanic women was associated with incident hypertension at year 3 follow-up (OR = 1.74; 95% CI 1.10–2.74) after adjustment for insurance and behavioral factors. However, further adjustment for clinical covariates attenuated the association. Analyses of psychosocial variables correlated with depression but did not alter findings. Low rates of antidepressant medication usage were also reported. Conclusions In the largest longitudinal study to date of older Hispanic women which included physiologic, behavioral and psychosocial moderators of depression, there was no association between baseline

  11. Downhole pressure attenuation apparatus

    SciTech Connect

    Ricles, T.D.; Barton, J.A.

    1992-02-18

    This patent describes a process for preventing damage to tool strings and other downhole equipment in a well caused by pressures produced during detonation of one or more downhole explosive devices. It comprises adding to a tool string at least one pressure attenuating apparatus for attenuating the peak pressure wave and quasi-static pressure pulse produced by the explosive devices, the pressure attenuating apparatus including an initially closed relief vent including tubing means supporting a plurality of charge port assemblies each including an explosive filled shaped charge and a prestressed disc, the shaped charges interconnected by a detonating cord, the amount of explosive in each shaped charge being sufficient to rupture its associated disc without damaging surrounding tubular bodies in the well, and a vent chamber defined by the tubing means and providing a liquid free volume, and opening the relief vent substantially contemporaneously with downhole explosive device detonation by detonating the shaped charges to rupture the discs of the charge port assemblies.

  12. Protection of the blood-brain barrier by hypercapnia during acute hypertension

    SciTech Connect

    Baumbach, G.L.; Mayhan, W.G.; Heistad, D.D.

    1986-08-01

    The purpose of this study was to examine effects of hypercapnia on susceptibility of the blood-brain barrier to disruption during acute hypertension. Two methods were used to test the hypothesis that cerebral vasodilation during hypercapnia increases disruption of the blood-brain barrier. First, permeability of the blood-brain barrier was measured in anesthetized cats with SVI-labeled serum albumin. Severe hypertension markedly increased permeability of the blood-brain barrier during normocapnia, but not during hypercapnia. The protective effect of hypercapnia was not dependent on sympathetic nerves. Second, in anesthetized rats, permeability of the barrier was quantitated by clearance of fluorescent dextran. Disruption of the blood-brain barrier during hypertension was decreased by hypercapnia. Because disruption of the blood-brain barrier occurred primarily in pial venules, the authors also measured pial venular diameter and pressure. Acute hypertension increased pial venular pressure and diameter in normocapnic rats. Hypercapnia alone increased pial venular pressure and pial venular diameter, and acute hypertension during hypercapnia further increased venular pressure. The magnitude of increase in pial venular pressure during acute hypertension was significantly less in hypercapnic than in normocapnic rats. They conclude that hypercapnia protects the blood-brain barrier. Possible mechanisms of this effect include attenuation of the incremental increase in pial venular pressure by hypercapnia or a direct effect on the blood-brain barrier not related to venous pressure.

  13. Nebivolol has a beneficial effect in monocrotaline-induced pulmonary hypertension.

    PubMed

    Pankey, Edward A; Edward, Justin A; Swan, Kevin W; Bourgeois, Camille R T; Bartow, Matthew J; Yoo, Daniel; Peak, Taylor A; Song, Bryant M; Chan, Ryan A; Murthy, Subramanyam N; Prieto, Minolfa C; Giles, Thomas D; Kadowitz, Philip J

    2016-07-01

    Pulmonary hypertension is a rare disorder that, without treatment, is progressive and fatal within 3-4 years. Current treatment involves a diverse group of drugs that target the pulmonary vascular bed. In addition, strategies that increase nitric oxide (NO) formation have a beneficial effect in rodents and patients. Nebivolol, a selective β1 adrenergic receptor-blocking agent reported to increase NO production and stimulate β3 receptors, has vasodilator properties suggesting that it may be beneficial in the treatment of pulmonary hypertension. The present study was undertaken to determine whether nebivolol has a beneficial effect in monocrotaline-induced (60 mg/kg) pulmonary hypertension in the rat. These results show that nebivolol treatment (10 mg/kg, once or twice daily) attenuates pulmonary hypertension, reduces right ventricular hypertrophy, and improves pulmonary artery remodeling in monocrotaline-induced pulmonary hypertension. This study demonstrates the presence of β3 adrenergic receptor immunoreactivity in pulmonary arteries and airways and that nebivolol has pulmonary vasodilator activity. Studies with β3 receptor agonists (mirabegron, BRL 37344) and antagonists suggest that β3 receptor-mediated decreases in systemic arterial pressure occur independent of NO release. Our results suggest that nebivolol, a selective vasodilating β1 receptor antagonist that stimulates β3 adrenergic receptors and induces vasodilation by increasing NO production, may be beneficial in treating pulmonary hypertensive disorders. PMID:27172427

  14. Taurine supplementation in spontaneously hypertensive rats: Advantages and limitations for human applications

    PubMed Central

    Suwanich, Atchariya; Wyss, J Michael; Roysommuti, Sanya

    2013-01-01

    Taurine (2-aminoethanesulfonic acid) is a β-amino acid found in many tissues particularly brain, myocardium, and kidney. It plays several physiological roles including cardiac contraction, antioxidation, and blunting of hypertension. Though several lines of evidence indicate that dietary taurine can reduce hypertension in humans and in animal models, evidence that taurine supplementation reduces hypertension in humans has not been conclusive. One reason for the inconclusive nature of past studies may be that taurine having both positive and negative effects on cardiovascular system depending on when it is assessed, some effects may occur early, while others only appear later. Further, other consideration may play a role, e.g., taurine supplementation improves hypertension in spontaneously hypertensive rats on a low salt diet but fails to attenuate hypertension on a high salt diet. In humans, some epidemiologic studies indicate that people with high taurine and low salt diets display lower arterial pressure than those with low taurine and high salt diets. Differences in techniques for measuring arterial pressure, duration of treatment, and animal models likely affect the response in different studies. This review considers both the positive and negative effects of taurine on blood pressure in animal models and their applications for human interventions. PMID:24340138

  15. The A2B adenosine receptor modulates pulmonary hypertension associated with interstitial lung disease.

    PubMed

    Karmouty-Quintana, Harry; Zhong, Hongyan; Acero, Luis; Weng, Tingting; Melicoff, Ernestina; West, James D; Hemnes, Anna; Grenz, Almut; Eltzschig, Holger K; Blackwell, Timothy S; Xia, Yang; Johnston, Richard A; Zeng, Dewan; Belardinelli, Luiz; Blackburn, Michael R

    2012-06-01

    Development of pulmonary hypertension is a common and deadly complication of interstitial lung disease. Little is known regarding the cellular and molecular mechanisms that lead to pulmonary hypertension in patients with interstitial lung disease, and effective treatment options are lacking. The purpose of this study was to examine the adenosine 2B receptor (A(2B)R) as a regulator of vascular remodeling and pulmonary hypertension secondary to pulmonary fibrosis. To accomplish this, cellular and molecular changes in vascular remodeling were monitored in mice exposed to bleomycin in conjunction with genetic removal of the A(2B)R or treatment with the A(2B)R antagonist GS-6201. Results demonstrated that GS-6201 treatment or genetic removal of the A(2B)R attenuated vascular remodeling and hypertension in our model. Furthermore, direct A(2B)R activation on vascular cells promoted interleukin-6 and endothelin-1 release. These studies identify a novel mechanism of disease progression to pulmonary hypertension and support the development of A(2B)R antagonists for the treatment of pulmonary hypertension secondary to interstitial lung disease. PMID:22415303

  16. [Postpartum pulmonary hypertension].

    PubMed

    Escalante, Juan Pablo; Diez, Ana; Figueroa Casas, Marcelo; Lasave, Alejandro; Cursack, Guillermo; Poy, Carlos; Rodríguez, María Soledad; Galuppo, Marcela; Zapata, Gerardo

    2015-01-01

    Pulmonary hypertension (PH) in pregnancy is a rare disorder that carries a high risk to mother and child, and as such, it is considered a contraindication to becoming pregnant. However, there are few published reports related to the diagnosis of this condition after delivery. We describe three PH cases diagnosed after their normal pregnancies and deliveries. Although the causes are unknown, several mechanisms such as hypercoagulation, placental hypoxia or amniotic fluid embolism have been considered as possible causes. It is difficult to define whether a PH diagnosed in the postpartum period, relates to an earlier asymptomatic PH period that was triggered by the physiological stress of labor or if it is a recently acquired condition. Despite the lack of data to support the absence of PH previous to pregnancy in our three patients, lack of events during this period, asymptomatic and normal deliveries, lead us to believe that they did not suffer this disease prior to pregnancy; considering that high hemodynamic demands impair a ventricle with little reserve, and its subsequent appearance at time of delivery. PMID:25637900

  17. Developmental programming and hypertension

    PubMed Central

    Nuyt, Anne Monique; Alexander, Barbara T.

    2009-01-01

    Purpose of review There is a growing body of evidence linking adverse events or exposures during early life and adult-onset diseases. After important epidemiological studies from many parts of the world, research now focuses on mechanisms of organ dysfunction and on refining the understanding of the interaction between common elements of adverse perinatal conditions, such as nutrition, oxidants, and toxins exposures. This review will focus on advances in our comprehension of developmental programming of hypertension. Recent findings Recent studies have unraveled important mechanisms of oligonephronia and impaired renal function, altered vascular function and structure as well as sympathetic regulation of the cardiovascular system. Furthermore, interactions between prenatal insults and postnatal conditions are the subject of intensive research. Prematurity vs. intrauterine growth restriction modulate differently programming of high blood pressure. Along with antenatal exposure to glucocorticoids and imbalanced nutrition, a critical role for perinatal oxidative stress is emerging. Summary While the complexity of the interactions between antenatal and postnatal influences on adult blood pressure is increasingly recognized, the importance of postnatal life in (positively) modulating developmental programming offers the hope of a critical window of opportunity to reverse programming and prevent or reduce related adult-onset diseases. PMID:19434052

  18. Flexible graphene based microwave attenuators.

    PubMed

    Byun, Kisik; Ju Park, Yong; Ahn, Jong-Hyun; Min, Byung-Wook

    2015-02-01

    We demonstrate flexible 3 dB and 6 dB microwave attenuators using multilayer graphene grown by the chemical vapor deposition method. On the basis of the characterized results of multilayer graphene and graphene-Au ohmic contacts, the graphene attenuators are designed and measured. The flexible graphene-based attenuators have 3 dB and 6 dB attenuation with a return loss of less than -15 dB at higher than 5 GHz. The devices have shown durability in a bending cycling test of 100 times. The circuit model of the attenuator based on the characterized results matches the experimental results well. PMID:25590144

  19. Control algorithms for dynamic attenuators

    SciTech Connect

    Hsieh, Scott S.; Pelc, Norbert J.

    2014-06-15

    Purpose: The authors describe algorithms to control dynamic attenuators in CT and compare their performance using simulated scans. Dynamic attenuators are prepatient beam shaping filters that modulate the distribution of x-ray fluence incident on the patient on a view-by-view basis. These attenuators can reduce dose while improving key image quality metrics such as peak or mean variance. In each view, the attenuator presents several degrees of freedom which may be individually adjusted. The total number of degrees of freedom across all views is very large, making many optimization techniques impractical. The authors develop a theory for optimally controlling these attenuators. Special attention is paid to a theoretically perfect attenuator which controls the fluence for each ray individually, but the authors also investigate and compare three other, practical attenuator designs which have been previously proposed: the piecewise-linear attenuator, the translating attenuator, and the double wedge attenuator. Methods: The authors pose and solve the optimization problems of minimizing the mean and peak variance subject to a fixed dose limit. For a perfect attenuator and mean variance minimization, this problem can be solved in simple, closed form. For other attenuator designs, the problem can be decomposed into separate problems for each view to greatly reduce the computational complexity. Peak variance minimization can be approximately solved using iterated, weighted mean variance (WMV) minimization. Also, the authors develop heuristics for the perfect and piecewise-linear attenuators which do not requirea priori knowledge of the patient anatomy. The authors compare these control algorithms on different types of dynamic attenuators using simulated raw data from forward projected DICOM files of a thorax and an abdomen. Results: The translating and double wedge attenuators reduce dose by an average of 30% relative to current techniques (bowtie filter with tube current

  20. Ultrasonic attenuation in pearlitic steel.

    PubMed

    Du, Hualong; Turner, Joseph A

    2014-03-01

    Expressions for the attenuation coefficients of longitudinal and transverse ultrasonic waves are developed for steel with pearlitic microstructure. This type of lamellar duplex microstructure influences attenuation because of the lamellar spacing. In addition, longitudinal attenuation measurements were conducted using an unfocused transducer with 10 MHz central frequency on the cross section of a quenched railroad wheel sample. The dependence of longitudinal attenuation on the pearlite microstructure is observed from the changes of longitudinal attenuation from the quenched tread surface to deeper locations. The results show that the attenuation value is lowest and relatively constant within the quench depth, then increases linearly. The experimental results demonstrate a reasonable agreement with results from the theoretical model. Ultrasonic attenuation provides an important non-destructive method to evaluate duplex microstructure within grains which can be implemented for quality control in conjunction with other manufacturing processes. PMID:24268679

  1. New therapies for arterial hypertension.

    PubMed

    Pagliaro, Beniamino; Santolamazza, Caterina; Rubattu, Speranza; Volpe, Massimo

    2016-03-01

    Arterial hypertension is the most common chronic disease in developed countries and it is the leading risk factor for stroke, ischemic heart disease, congestive heart failure, chronic renal failure and peripheral artery disease. Its prevalence appears to be about 30-45% of the general population. Recent European guidelines estimate that up to 15-20% of the hypertensive patients are not controlled on a dual antihypertensive combination and they require three or more different antihypertensive drug classes to achieve adequate blood pressure control. The guidelines confirmed that diuretics, beta-blockers, calcium-channel blockers, angiotensin-converting enzyme inhibitors and angiotensin receptor blockers are suitable for the initiation and maintenance of antihypertensive treatment, either as monotherapy or in combination therapy. Very few antihypertensive agents have reached the market over the last few years, but no new therapeutic class has really emerged. The long-term adherence to cardiovascular drugs is still low in both primary and secondary prevention of cardiovascular diseases. In particular, the issue of compliance is persistently high in hypertension, despite the fixed-dose combination therapy. As a consequence, a cohort of high-risk hypertensive population, represented by patients affected by refractory and resistant hypertension, can be identified. Therefore, the need of controlling BP in high-risk patients may be addressed, in part, by the development of new drugs, devices and procedures that are designed to treat hypertension and comorbidities. In this review we will comprehensively discuss the current literature on recent therapeutic advances in hypertension, including both medical therapy and interventional procedures. PMID:26730462

  2. Combination treatment with a calcium channel blocker and an angiotensin blocker in a rat systolic heart failure model with hypertension.

    PubMed

    Namba, Masashi; Kim, Shokei; Zhan, Yumei; Nakao, Takafumi; Iwao, Hiroshi

    2002-05-01

    The mechanism and treatment of hypertensive systolic heart failure are not well defined. We compared the effect of an angiotensin-converting enzyme inhibitor (cilazapril, 10 mg/kg), an angiotensin receptor blocker (candesartan, 3 mg/kg), a calcium channel blocker (benidipine, 1, 3 or 6 mg/kg), and the same calcium channel blocker combined with renin-angiotensin blockers on systolic heart failure in Dahl salt-sensitive (DS) rats. DS rats were fed an 8% Na diet from 6 weeks of age and then subjected to the above drug treatments. Benidipine (1 mg/kg), cilazapril, and candesartan had compatible hypotensive effects and similar beneficial effects on cardiac hypertrophy, gene expression, and survival rate. The combination of benidipine with cilazapril or candesartan was found to have no additional beneficial effects on the above parameters, with the exception of a reduction in atrial natriuretic polypeptide gene expression. On the other hand, candesartan normalized serum creatinine, but serum creatinine was unaffected by either benidipine at 1 or 3 mg/kg or cilazapril. Further, the combined use of benidipine and either candesartan or cilazapril resulted in an additional reduction of urinary albumin excretion in DS rats. Thus systolic heart failure in DS rats is mainly mediated by hypertension, while renal dysfunction of DS rats is due to both hypertension and the AT1 receptor itself. These findings suggest that the combination of a calcium channel blocker with an AT1 receptor blocker or ACE inhibitor may be more effective in treating the renal dysfunction associated with systolic heart failure than monotherapy with either agent alone. However, further studies will be needed before reaching any definitive conclusion on the efficacy of this combination therapy in patients with heart failure. PMID:12135327

  3. Comprehensive management of hypertensive emergencies and urgencies.

    PubMed

    Mansoor, George A; Frishman, William H

    2002-01-01

    Despite advances in chronic hypertension management, hypertensive emergencies and urgencies remain as serious complications. Much of this relates to poor compliance with effective antihypertensive management. Hypertensive emergencies and urgencies can also be seen as the initial manifestations of hypertension in pregnancy and in the perioperative period. Multiple classes of intravenous antihypertensive drugs are available to treat hypertensive emergencies, and specific agents may have an advantage in a given clinical situation. Orally active agents are used to treat hypertensive urgencies, and include clonidine, angiotensin-converting enzyme inhibitors, and labetalol. Most patients respond to drug therapy, but problems may arise related to a rapid normalization of blood pressure. PMID:12441013

  4. Hyperthyroidism and pulmonary hypertension.

    PubMed

    Marvisi, M; Brianti, M; Marani, G; Del Borello, R; Bortesi, M L; Guariglia, A

    2002-04-01

    In recent years, many authors have described several cases revealing an association between hyperthyroidism and pulmonary hypertension (PH). This observational study was designed to evaluate the incidence of PH in hyperthyroidism and was set in a department of internal medicine and pulmonary diseases with an out-patients department of endocrinology. Thirty-four patients, 25 women and nine men, with a mean age of 38 +/- 15 SD years participated. Twenty had Graves' disease and 14 had a nodular goitre. The patients were divided into two equally matched groups: those with a recently diagnosed hyperthyroidism, taking no drugs (group 1; n = 17) and those in a euthyroid state taking methimazole (group 2; n= 17). Transthoracic Doppler echocardiography was performed and systolic pulmonary artery pressurements of (PAPs) was determined by the tricuspid regurgitation method using the Bernoulli equation. Measurements of triiodothyronine, tetraiodothyronine, free thyroxine (Ft4), thyroid-stimulating hormone (TSH) and antithyroglobulin and antimicrosomal antibodies were also taken. We found a mild PH in seven patients of group 1 and in none of group 2. The mean +/- SD systolic pulmonaryartery pressurewas 28.88 +/- 6.41 in group 1 and 22.53 +/- 1.84 ingroup 2 (P<0.0001). A correlation was found between the TSH value and PAPs (r = -082;P < 0.001) and Ft4 and PAPs (r = 0 85; P < 0.001) in group 1. These findings indicate the presence of a frequent association between PH and hyperthyroidism. We suggest that hyperthyroidism be included in the differential diagnosis of PH. PMID:11999999

  5. Heat stress proteins in hypertension

    SciTech Connect

    Malo, D.; Tremblay, J.; Pang, S.C.; Schlager, G.; Hamet, P.

    1986-03-05

    It has been described that spontaneously hypertensive rats (SHR) are more sensitive to an acute environmental heat stress and that cultured cardiomyocytes from neonatal SHR are demonstrated to be more thermosensitive. In addition, chronically heat exposed spontaneously hypertensive mice leads to a decrease of blood pressure in these animals. Heat shock is known to induce the synthesis of a new set of proteins (HSP) in every cell tested. This ubiquitous response seems to be involved in the induction of a thermotolerant state. The synthesis of 70K HSP was observed in lymphocytes isolated from the spleen of chronically heated mice. They used lymphocytes, previously isolated on a ficoll gradient, to evaluate the HSP induction in normotensive (WKY) and hypertensive (SHR) rats. The heat shock was induced by exposing the lymphocytes at 46/sup 0/C during 5 min in a hot water bath. The cells were then labeled with (/sup 75/Se)-methionine, washed, homogenized and separated on 5-30% SDS-polyacrylamide gel. Preliminary results suggest an abnormal pattern of induction of 70K and 90K HSP in hypertension. Heat sensitivity, thermotolerance and expression of HSP may, thus, be related to hypertension.

  6. Salt intake and hypertension therapy.

    PubMed

    Milan, Alberto; Mulatero, Paolo; Rabbia, Franco; Veglio, Franco

    2002-01-01

    Hypertension is a risk factor for cardiovascular and renal organ damage. Environmental conditions affect the development of high blood pressure (BP), although genetic influences are also important. Current international guidelines recommend reducing dietary sodium to no more than 100 mmol (about 2.4 g sodium or approximately 6 g salt) per day to prevent BP rising; the current intake of sodium in industrialized countries is approximately double the recommended amount. Clinical trials (DASH and TOHP studies) have shown that dietary factors are fundamental in the prevention and control of BP. Low dietary sodium intake is particularly effective in preventing hypertension in subjects with an increased risk such as the overweight, borderline hypertensives or the elderly. A low-salt diet combined with anti-hypertensive therapies facilitates BP reduction independent of race. The hypotensive effect of calcium channel blockers is less dependent on salt intake than other drugs, such as ACE inhibitors or diuretics. Reduced sodium intake associated with other dietary changes (such as weight loss, and increasing potassium, calcium and magnesium intake) are important instruments for the prevention and therapy of hypertension. PMID:11936420

  7. Pharmacology of the Adenosine A3 Receptor in the Vasculature and Essential Hypertension

    PubMed Central

    Ho, Ming-Fen; Low, Leanne M.; Rose’Meyer, Roselyn B.

    2016-01-01

    Background Essential hypertension is considered to be a multifactorial disorder and its aetiology has yet to be clearly identified. As the adenosine receptors have a significant role in mediating vasodilation, alterations in their structures or signalling pathways may be involved in the development of hypertension. This study aimed to measure the expression of adenosine A3 receptors in a range of cardiovascular tissues and determine whether they could be altered with essential hypertension, and to functionally test responses to adenosine A3 receptor agonists in coronary blood vessels using the isolated perfused heart preparation. Methods mRNA samples from cardiovascular tissues and a range of blood vessels were collected from 10 week old male spontaneously hypertensive rats and age-gender matched Wistar rats (n = 8). The Langendorff heart perfusion preparation was used to characterise adenosine A3 receptor mediated coronary vasodilation in the rat heart. Results Adenosine A3 receptor agonists induced coronary vasodilation. The expression of adenosine A3 receptors in cardiovascular tissues was altered in a tissue-specific pattern. Specifically, down-regulation of adenosine A3 receptor expression occurred in hypertensive hearts, which might be associated with attenuated vasodilator responses observed in coronary vessels to adenosine A3 receptor agonists. Conclusions This study demonstrated alterations in the expression of adenosine A3 receptors occurred in a tissue specific mode, and reduced adenosine A3 receptor mediated coronary vasodilation in hearts from spontaneously hypertensive rats. Our findings with regard to changes in the adenosine A3 receptor in hypertensive hearts suggest that adenosine A3 receptor might play a role in the physiopathology of essential hypertension and potentially open the way to pharmacologic manipulation of vasomotor activity by the use of adenosine A3 receptor agonists. PMID:26907173

  8. Alcohol consumption and the risk of hypertension in women and men.

    PubMed

    Sesso, Howard D; Cook, Nancy R; Buring, Julie E; Manson, JoAnn E; Gaziano, J Michael

    2008-04-01

    Heavy alcohol intake increases the risk of hypertension, but the relationship between light-to-moderate alcohol consumption and incident hypertension remains controversial. We prospectively followed 28 848 women from the Women's Health Study and 13 455 men from the Physicians' Health Study free of baseline hypertension, cardiovascular disease, and cancer. Self-reported lifestyle and clinical risk factors were collected. In women, total alcohol intake was summed from liquor, red wine, white wine, and beer; men reported total alcohol intake from a single combined question. During 10.9 and 21.8 years of follow-up, 8680 women and 6012 men developed hypertension (defined as new physician diagnosis, antihypertensive treatment, reported systolic blood pressure >or=140 mm Hg, or diastolic blood pressure >or=90 mm Hg). In women, we found a J-shaped association between alcohol intake and hypertension in age- and lifestyle-adjusted models. Adding potential intermediates (body mass index, diabetes, and high cholesterol) attenuated the benefits of alcohol in the light-to-moderate range and strengthened the adverse effects of heavy alcohol intake. Beverage-specific relative risks paralleled those for total alcohol intake. In men, alcohol intake was positively and significantly associated with the risk of hypertension and persisted after multivariate adjustment. Models stratified by baseline systolic blood pressure (<120 versus >or=120 mm Hg) or diastolic blood pressure (<75 versus >or=75 mm Hg) did not alter the relative risks in women and men. In conclusion, light-to-moderate alcohol consumption decreased hypertension risk in women and increased risk in men. The threshold above which alcohol became deleterious for hypertension risk emerged at >or=4 drinks per day in women versus a moderate level of >or=1 drink per day in men. PMID:18259032

  9. Elafin Reverses Pulmonary Hypertension via Caveolin-1–Dependent Bone Morphogenetic Protein Signaling

    PubMed Central

    Nickel, Nils P.; Spiekerkoetter, Edda; Gu, Mingxia; Li, Caiyun G.; Li, Hai; Kaschwich, Mark; Diebold, Isabel; Hennigs, Jan K.; Kim, Ki-Yoon; Miyagawa, Kazuya; Wang, Lingli; Cao, Aiqin; Sa, Silin; Jiang, Xinguo; Stockstill, Raymond W.; Nicolls, Mark R.; Zamanian, Roham T.; Bland, Richard D.

    2015-01-01

    Rationale: Pulmonary arterial hypertension is characterized by endothelial dysfunction, impaired bone morphogenetic protein receptor 2 (BMPR2) signaling, and increased elastase activity. Synthetic elastase inhibitors reverse experimental pulmonary hypertension but cause hepatotoxicity in clinical studies. The endogenous elastase inhibitor elafin attenuates hypoxic pulmonary hypertension in mice, but its potential to improve endothelial function and BMPR2 signaling, and to reverse severe experimental pulmonary hypertension or vascular pathology in the human disease was unknown. Objectives: To assess elafin-mediated regression of pulmonary vascular pathology in rats and in lung explants from patients with pulmonary hypertension. To determine if elafin amplifies BMPR2 signaling in pulmonary artery endothelial cells and to elucidate the underlying mechanism. Methods: Rats with pulmonary hypertension induced by vascular endothelial growth factor receptor blockade and hypoxia (Sugen/hypoxia) as well as lung organ cultures from patients with pulmonary hypertension were used to assess elafin-mediated reversibility of pulmonary vascular disease. Pulmonary arterial endothelial cells from patients and control subjects were used to determine the efficacy and mechanism of elafin-mediated BMPR2 signaling. Measurements and Main Results: In Sugen/hypoxia rats, elafin reduced elastase activity and reversed pulmonary hypertension, judged by regression of right ventricular systolic pressure and hypertrophy and pulmonary artery occlusive changes. Elafin improved endothelial function by increasing apelin, a BMPR2 target. Elafin induced apoptosis in human pulmonary arterial smooth muscle cells and decreased neointimal lesions in lung organ culture. In normal and patient pulmonary artery endothelial cells, elafin promoted angiogenesis by increasing pSMAD-dependent and -independent BMPR2 signaling. This was linked mechanistically to augmented interaction of BMPR2 with caveolin-1 via

  10. Digitally Controlled Beam Attenuator

    NASA Astrophysics Data System (ADS)

    Peppler, W. W.; Kudva, B.; Dobbins, J. T.; Lee, C. S.; Van Lysel, M. S.; Hasegawa, B. H.; Mistretta, C. A.

    1982-12-01

    In digital fluorographic techniques the video camera must accommodate a wide dynamic range due to the large variation in the subject thickness within the field of view. Typically exposure factors and the optical aperture are selected such that the maximum video signal is obtained in the most transmissive region of the subject. Consequently, it has been shown that the signal-to-noise ratio is severely reduced in the dark regions. We have developed a prototype digital beam attenuator (DBA) which will alleviate this and some related problems in digital fluorography. The prototype DBA consists of a 6x6 array of pistons which are individually controlled. A membrane containing an attenuating solu-tion of (CeC13) in water and the piston matrix are placed between the x-ray tube and the subject. Under digital control the pistons are moved into the attenuating material in order to adjust the beam intensity over each of the 36 cells. The DBA control unit which digitizes the image during patient positioning will direct the pistons under hydraulic control to produce a uniform x-ray field exiting the subject. The pistons were designed to produce very little structural background in the image. In subtraction studies any structure would be cancelled. For non-subtraction studies such as cine-cardiology we are considering higher cell densities (eg. 64x64). Due to the narrow range of transmission provided by the DBA, in such studies ultra-high contrast films could be used to produce a high resolution quasi-subtraction display. Additional benefits of the DBA are: 1) reduced dose to the bright image areas when the dark areas are properly exposed. 2) improved scatter and glare to primary ratios, leading to improved contrast in the dark areas.

  11. Loss of functional endothelial connexin40 results in exercise-induced hypertension in mice.

    PubMed

    Morton, Susan K; Chaston, Daniel J; Howitt, Lauren; Heisler, Jillian; Nicholson, Bruce J; Fairweather, Stephen; Bröer, Stefan; Ashton, Anthony W; Matthaei, Klaus I; Hill, Caryl E

    2015-03-01

    During activity, coordinated vasodilation of microcirculatory networks with upstream supply vessels increases blood flow to skeletal and cardiac muscles and reduces peripheral resistance. Endothelial dysfunction in humans attenuates activity-dependent vasodilation, resulting in exercise-induced hypertension in otherwise normotensive individuals. Underpinning activity-dependent hyperemia is an ascending vasodilation in which the endothelial gap junction protein, connexin (Cx)40, plays an essential role. Because exercise-induced hypertension is proposed as a forerunner to clinical hypertension, we hypothesized that endothelial disruption of Cx40 function in mice may create an animal model of this condition. To this end, we created mice in which a mutant Cx40T152A was expressed alongside wildtype Cx40 selectively in the endothelium. Expression of the Cx40T152A transgene in Xenopus oocytes and mouse coronary endothelial cells in vitro impaired both electric and chemical conductance and acted as a dominant-negative against wildtype Cx40, Cx43, and Cx45, but not Cx37. Endothelial expression of Cx40T152A in Cx40T152ATg mice attenuated ascending vasodilation, without effect on radial coupling through myoendothelial gap junctions. Using radiotelemetry, Cx40T152ATg mice showed an activity-dependent increase in blood pressure, which was significantly greater than in wildtype mice, but significantly less than in chronically hypertensive, Cx40knockout mice. The increase in heart rate with activity was also greater than in wildtype or Cx40knockout mice. We conclude that the endothelial Cx40T152A mutation attenuates activity-dependent vasodilation, producing a model of exercise-induced hypertension. These data highlight the importance of endothelial coupling through Cx40 in regulating blood pressure during activity. PMID:25547341

  12. Radiation Imaging and Attenuation

    NASA Astrophysics Data System (ADS)

    Davison, Candace; Yocum, Douglas

    2008-03-01

    X-ray and neutron images are used to demonstrate materials' different radiation attenuation properties. This leads to discussion of applications in medicine, industry and research. The Penn State Radiation Science and Engineering Center (RSEC) uses neutron radioscopy to image the inside of a working hydrogen fuel cell. This is one of the many educational activities that are conducted when students visit the RSEC. To encourage pre-college students to apply these principles and learn more about nuclear technology, we are sponsoring a design competition. For more information visit www.rsec.psu.edu

  13. Who Is at Risk for Pulmonary Hypertension?

    MedlinePlus

    ... exact number of people who have pulmonary hypertension (PH) isn't known. Group 1 pulmonary arterial hypertension ( ... have group 1 PAH tend to be overweight . PH that occurs with another disease or condition is ...

  14. Infantile Renovascular Hypertension with Failure to Thrive.

    PubMed

    Phillips, Amanda R; Eliason, Jonathan L; Stanley, James C; Coleman, Dawn M

    2016-05-01

    Severe hypertension in infancy is a rare cause of failure to thrive. The successful surgical management of this disease in an infant having refractory renovascular hypertension and growth failure is reported. PMID:26965798

  15. An Update on Inpatient Hypertension Management.

    PubMed

    Axon, R Neal; Turner, Mason; Buckley, Ryan

    2015-11-01

    Hypertension is highly prevalent affecting nearly one third of the US adult population. Though generally approached as an outpatient disorder, elevated blood pressure is observed in a majority of hospitalized patients. The spectrum of hypertensive disease ranges from patients with hypertensive emergency including markedly elevated blood pressure and associated end-organ damage to asymptomatic patients with minimally elevated pressures of unclear significance. It is important to note that current evidence-based hypertension guidelines do not specifically address inpatient hypertension. This narrative review focuses primarily on best practices for diagnosing and managing nonemergent hypertension in the inpatient setting. We describe examples of common hypertensive syndromes, provide suggestions for optimal post-acute management, and point to evidence-based or consensus guidelines where available. In addition, we describe a practical approach to managing asymptomatic elevated blood pressure observed in the inpatient setting. Finally, arranging effective care transitions to ensure optimal ongoing hypertension management is appropriate in all cases. PMID:26362300

  16. Pressure Points: Preventing and Controlling Hypertension

    MedlinePlus

    ... Issue Past Issues Pressure Points: Preventing and Controlling Hypertension Past Issues / Summer 2006 Table of Contents For ... diagnosed with high blood pressure." Aditional Information On Hypertension MedlinePlus: High blood pressure: http://www.nlm.nih. ...

  17. Microarray analysis in pulmonary hypertension

    PubMed Central

    Hoffmann, Julia; Wilhelm, Jochen; Olschewski, Andrea

    2016-01-01

    Microarrays are a powerful and effective tool that allows the detection of genome-wide gene expression differences between controls and disease conditions. They have been broadly applied to investigate the pathobiology of diverse forms of pulmonary hypertension, namely group 1, including patients with idiopathic pulmonary arterial hypertension, and group 3, including pulmonary hypertension associated with chronic lung diseases such as chronic obstructive pulmonary disease and idiopathic pulmonary fibrosis. To date, numerous human microarray studies have been conducted to analyse global (lung homogenate samples), compartment-specific (laser capture microdissection), cell type-specific (isolated primary cells) and circulating cell (peripheral blood) expression profiles. Combined, they provide important information on development, progression and the end-stage disease. In the future, system biology approaches, expression of noncoding RNAs that regulate coding RNAs, and direct comparison between animal models and human disease might be of importance. PMID:27076594

  18. QT dispersion in adult hypertensives.

    PubMed Central

    Sani, Isa Muhammad; Solomon, Danbauchi Sulei; Imhogene, Oyati Albert; Ahmad, Alhassan Muhammad; Bala, Garko Sani

    2006-01-01

    Increased QT dispersion is associated with sudden cardiac death in congestive cardiac failure, hypertrophic cardiomyopathy and following myocardial infarction. Patients with hypertension--in particular, those with left ventricular hypertrophy (LVH)--are also at greater risk of sudden cardiac death. We examined whether QT dispersion, which is easily obtained from a routine ECG, correlates with LVH. One-hundred untreated patients with systemic hypertension and 78 normotensives had QT dispersion measured manually from a surface 12-lead electrocardiogram and two-dimensional echocardiography performed to measure interventricular septal thickness, posterior wall thickness and left ventricular internal diameter. Office blood pressure was also recorded. Multivariate analysis demonstrated significant relationships between QT dispersion and office systolic blood pressure, and left ventricular mass index. Manual measurement of QT dispersion might be a simple, noninvasive screening procedure to identify those hypertensives at greatest risk of sudden cardiac death in a third-world country. PMID:16623077

  19. Microarray analysis in pulmonary hypertension.

    PubMed

    Hoffmann, Julia; Wilhelm, Jochen; Olschewski, Andrea; Kwapiszewska, Grazyna

    2016-07-01

    Microarrays are a powerful and effective tool that allows the detection of genome-wide gene expression differences between controls and disease conditions. They have been broadly applied to investigate the pathobiology of diverse forms of pulmonary hypertension, namely group 1, including patients with idiopathic pulmonary arterial hypertension, and group 3, including pulmonary hypertension associated with chronic lung diseases such as chronic obstructive pulmonary disease and idiopathic pulmonary fibrosis. To date, numerous human microarray studies have been conducted to analyse global (lung homogenate samples), compartment-specific (laser capture microdissection), cell type-specific (isolated primary cells) and circulating cell (peripheral blood) expression profiles. Combined, they provide important information on development, progression and the end-stage disease. In the future, system biology approaches, expression of noncoding RNAs that regulate coding RNAs, and direct comparison between animal models and human disease might be of importance. PMID:27076594

  20. Schistosomiasis-associated pulmonary hypertension

    PubMed Central

    Mocumbi, Ana Olga H.; Kim, Nick H.; Mandel, Jess

    2014-01-01

    Abstract Schistosomiasis, a parasite-borne disease, is highly prevalent in Africa and Asia; it is estimated that close to 20 million people worldwide have a severe form of the disease. The chronic form can affect the gastrointestinal system and lead to hepatosplenic disease, and it may cause cardiopulmonary complications, including pulmonary hypertension. The exact pathogenesis of schistosomiasis-associated pulmonary hypertension (Sch-PH) remains unclear, although several mechanisms, including parasitic arterial embolization, pulmonary arteriopathy, and portopulmonary hypertension–like pathophysiology, have been suggested. The immunopathology of the disease is also unclear, although there are similarities with the immunology of idiopathic pulmonary arterial hypertension (PAH). Finally, the treatment of Sch-PH has not been well studied. There is some evidence on treating the underlying infection, with unclear effect on Sch-PH, and advanced PAH therapies are now being suggested, but more studies are needed to confirm their efficacy. PMID:25610596

  1. Pharmacologic management of childhood hypertension.

    PubMed

    Sinaiko, A R

    1993-02-01

    Antihypertensive drug therapy is used in children primarily to treat secondary forms of hypertension, because the prevalence of essential hypertension in the first decade of life is considerably less than 1% of the childhood population. This prevalence increases during the second decade of life, but the percentage of teenagers with essential hypertension continues to be low. Pharmaceutical companies have been able to target drug development to specific physiologic and biochemical systems. The converting enzyme inhibitors and calcium-channel blockers have greatly improved the success of therapy concomitant with a reduction in the incidence of adverse effects. The result has been a major change during the past decade in the recommendations for antihypertensive drug therapy. PMID:8417406

  2. Upregulated Copper Transporters in Hypoxia-Induced Pulmonary Hypertension

    PubMed Central

    Zimnicka, Adriana M.; Tang, Haiyang; Guo, Qiang; Kuhr, Frank K.; Oh, Myung-Jin; Wan, Jun; Chen, Jiwang; Smith, Kimberly A.; Fraidenburg, Dustin R.; Choudhury, Moumita S. R.; Levitan, Irena; Machado, Roberto F.; Kaplan, Jack H.; Yuan, Jason X.-J.

    2014-01-01

    Pulmonary vascular remodeling and increased arterial wall stiffness are two major causes for the elevated pulmonary vascular resistance and pulmonary arterial pressure in patients and animals with pulmonary hypertension. Cellular copper (Cu) plays an important role in angiogenesis and extracellular matrix remodeling; increased Cu in vascular smooth muscle cells has been demonstrated to be associated with atherosclerosis and hypertension in animal experiments. In this study, we show that the Cu-uptake transporter 1, CTR1, and the Cu-efflux pump, ATP7A, were both upregulated in the lung tissues and pulmonary arteries of mice with hypoxia-induced pulmonary hypertension. Hypoxia also significantly increased expression and activity of lysyl oxidase (LOX), a Cu-dependent enzyme that causes crosslinks of collagen and elastin in the extracellular matrix. In vitro experiments show that exposure to hypoxia or treatment with cobalt (CoCl2) also increased protein expression of CTR1, ATP7A, and LOX in pulmonary arterial smooth muscle cells (PASMC). In PASMC exposed to hypoxia or treated with CoCl2, we also confirmed that the Cu transport is increased using 64Cu uptake assays. Furthermore, hypoxia increased both cell migration and proliferation in a Cu-dependent manner. Downregulation of hypoxia-inducible factor 1α (HIF-1α) with siRNA significantly attenuated hypoxia-mediated upregulation of CTR1 mRNA. In summary, the data from this study indicate that increased Cu transportation due to upregulated CTR1 and ATP7A in pulmonary arteries and PASMC contributes to the development of hypoxia-induced pulmonary hypertension. The increased Cu uptake and elevated ATP7A also facilitate the increase in LOX activity and thus the increase in crosslink of extracellular matrix, and eventually leading to the increase in pulmonary arterial stiffness. PMID:24614111

  3. Global and Renal-Specific Sympathoinhibition in Aldosterone Hypertension

    PubMed Central

    Lohmeier, Thomas E.; Liu, Boshen; Hildebrandt, Drew A.; Cates, Adam W.; Georgakopoulos, Dimitrios; Irwin, Eric D.

    2015-01-01

    Recent technology for chronic electrical activation of the carotid baroreflex and renal nerve ablation provide global and renal-specific suppression of sympathetic activity, respectively, but the conditions for favorable antihypertensive responses in resistant hypertension are unclear. Because inappropriately high plasma levels of aldosterone are prevalent in these patients, we investigated the effects of baroreflex activation and surgical renal denervation in dogs with hypertension induced by chronic infusion of aldosterone (12µg/kg/day). Under control conditions, basal values for mean arterial pressure and plasma norepinephrine concentration were 100±3 mm Hg and 134±26 pg/mL, respectively. By day 7 of baroreflex activation, plasma norepinephrine was reduced by ~ 40% and arterial pressure by 16±2 mmHg. All values returned to control levels during the recovery period. Arterial pressure increased to 122±5 mm Hg concomitant with a rise in plasma aldosterone concentration from 4.3±0.4 to 70.0±6.4 ng/dL after 14 days of aldosterone infusion, with no significant effect on plasma norepinephrine. After 7 days of baroreflex activation at control stimulation parameters, the reduction in plasma norepinephrine was similar but the fall in arterial pressure (7±1 mmHg) was diminished (~ 55%) during aldosterone hypertension as compared to control conditions. Despite sustained suppression of sympathetic activity, baroreflex activation did not have central actions to inhibit either the stimulation of vasopressin secretion or drinking induced by increased plasma osmolality during chronic aldosterone infusion. Finally, renal denervation did not attenuate aldosterone hypertension. These findings suggest that aldosterone excess may portend diminished blood pressure lowering to global and especially renal-specific sympathoinhibition during device-based therapy. PMID:25895584

  4. Global- and renal-specific sympathoinhibition in aldosterone hypertension.

    PubMed

    Lohmeier, Thomas E; Liu, Boshen; Hildebrandt, Drew A; Cates, Adam W; Georgakopoulos, Dimitrios; Irwin, Eric D

    2015-06-01

    Recent technology for chronic electric activation of the carotid baroreflex and renal nerve ablation provide global and renal-specific suppression of sympathetic activity, respectively, but the conditions for favorable antihypertensive responses in resistant hypertension are unclear. Because inappropriately high plasma levels of aldosterone are prevalent in these patients, we investigated the effects of baroreflex activation and surgical renal denervation in dogs with hypertension induced by chronic infusion of aldosterone (12 μg/kg per day). Under control conditions, basal values for mean arterial pressure and plasma norepinephrine concentration were 100±3 mm Hg and 134±26 pg/mL, respectively. By day 7 of baroreflex activation, plasma norepinephrine was reduced by ≈40% and arterial pressure by 16±2 mm Hg. All values returned to control levels during the recovery period. Arterial pressure increased to 122±5 mm Hg concomitant with a rise in plasma aldosterone concentration from 4.3±0.4 to 70.0±6.4 ng/dL after 14 days of aldosterone infusion, with no significant effect on plasma norepinephrine. After 7 days of baroreflex activation at control stimulation parameters, the reduction in plasma norepinephrine was similar but the fall in arterial pressure (7±1 mm Hg) was diminished (≈55%) during aldosterone hypertension when compared with control conditions. Despite sustained suppression of sympathetic activity, baroreflex activation did not have central actions to inhibit either the stimulation of vasopressin secretion or drinking induced by increased plasma osmolality during chronic aldosterone infusion. Finally, renal denervation did not attenuate aldosterone hypertension. These findings suggest that aldosterone excess may portend diminished blood pressure lowering to global and especially renal-specific sympathoinhibition during device-based therapy. PMID:25895584

  5. Treatment strategies for osteoarthritis patients with pain and hypertension.

    PubMed

    Verdecchia, Paolo; Angeli, Fabio; Mazzotta, Giovanni; Martire, Paola; Garofoli, Marta; Gentile, Giorgio; Reboldi, Gianpaolo

    2010-08-01

    Out of 100 patients with osteoarthritis (OA), almost 40 have a concomitant diagnosis of hypertension. Nonsteroidal anti-inflammatory drugs (NSAIDs) and cyclooxygenase-2 (COX-2) inhibitors may trigger a rise in blood pressure (BP), which is more marked in patients with established hypertension. NSAIDs and COX-2 inhibitors attenuate the antihypertensive effect of several antihypertensive agents. Frequent BP controls are needed in treated hypertensive patients who are concomitantly receiving NSAIDs or COX-2 inhibitors because even a small increase in BP may be associated with an important rise in the risk of major cardiovascular complications. In meta-analyses, an increase in systolic BP of 5mmHg was associated with a 25% higher risk of cardiovascular events. These data have been confirmed in randomized studies with rofecoxib and celecoxib, where a modest increase in BP was associated with a significantly higher risk of cardiovascular disease. There is emerging evidence that the COX-inhibiting nitric oxide donator (CINOD) class is promising in the treatment of patients with OA. Naproxcinod, the first CINOD investigated in clinical trials, is composed of the traditional NSAID naproxen covalently bound to the nitric oxide (NO)-donating moiety butanediol mono-nitrate (BDMN). The molecule has the potential to provide a sustained release of NO. In clinical studies, naproxcinod prevented the BP rise in normotensive and hypertensive patients observed with naproxen. The BP benefit of naproxcinod over naproxen was greater in patients concomitantly receiving angiotensin-converting enzyme inhibitors or angiotensin II receptor blockers. These investigational data suggest that naproxcinod is a valuable alternative to NSAIDs and COX-2 inhibitors for treatment of OA patients. PMID:22870450

  6. Treatment Strategies for Osteoarthritis Patients with Pain and Hypertension

    PubMed Central

    Verdecchia, Paolo; Angeli, Fabio; Mazzotta, Giovanni; Martire, Paola; Garofoli, Marta; Gentile, Giorgio; Reboldi, Gianpaolo

    2010-01-01

    Out of 100 patients with osteoarthritis (OA), almost 40 have a concomitant diagnosis of hypertension. Nonsteroidal anti-inflammatory drugs (NSAIDs) and cyclooxygenase-2 (COX-2) inhibitors may trigger a rise in blood pressure (BP), which is more marked in patients with established hypertension. NSAIDs and COX-2 inhibitors attenuate the antihypertensive effect of several antihypertensive agents. Frequent BP controls are needed in treated hypertensive patients who are concomitantly receiving NSAIDs or COX-2 inhibitors because even a small increase in BP may be associated with an important rise in the risk of major cardiovascular complications. In meta-analyses, an increase in systolic BP of 5mmHg was associated with a 25% higher risk of cardiovascular events. These data have been confirmed in randomized studies with rofecoxib and celecoxib, where a modest increase in BP was associated with a significantly higher risk of cardiovascular disease. There is emerging evidence that the COX-inhibiting nitric oxide donator (CINOD) class is promising in the treatment of patients with OA. Naproxcinod, the first CINOD investigated in clinical trials, is composed of the traditional NSAID naproxen covalently bound to the nitric oxide (NO)-donating moiety butanediol mono-nitrate (BDMN). The molecule has the potential to provide a sustained release of NO. In clinical studies, naproxcinod prevented the BP rise in normotensive and hypertensive patients observed with naproxen. The BP benefit of naproxcinod over naproxen was greater in patients concomitantly receiving angiotensin-converting enzyme inhibitors or angiotensin II receptor blockers. These investigational data suggest that naproxcinod is a valuable alternative to NSAIDs and COX-2 inhibitors for treatment of OA patients. PMID:22870450

  7. Refeeding hypertension in dietary obesity

    SciTech Connect

    Ernsberger, P.; Nelson, D.O. )

    1988-01-01

    A novel model of nutritionally induced hypertension in the rat is described. Dietary obesity was produced by providing sweet milk in addition to regular chow, which elicited a 52% increase in caloric intake. Despite 54% greater body weight gain and 139% heavier retroperitoneal fat pads, 120 days of overfeeding failed to increase systolic pressure in the conscious state or mean arterial pressure under urethan anesthesia. In contrast, mild hypertension developed in intermittantly fasted obese animals. The first 4-day supplemented fast was initiated 4 wk after the introduction of sweet milk, when the animals were 47 g overweight relative to chow-fed controls. Thereafter, 4 days of starvation were alternated with 2 wk of refeeding for a total of 4 cycles. A rapid fall in systolic blood pressure accompanied the onset of supplemented fasting and was maintained thereafter. With refeeding, blood pressure rose precipitously, despite poststarvation anorexia. Blood pressure tended to rise slightly over the remainder of the realimentation period. After the 4th supplemented fast, hypertension was sustained during 30 days of refeeding. Cumulative caloric intake in starved-refed rats fell within 2% of that in chow-fed controls. Refeeding hypertension appeared to be due to increased sympathetic nervous activity, since (1) cardiac {beta}-adrenergic receptors were downregulated, as indicated by a 40% decrease in the maximum binding of ({sup 3}H)dihydroalpranolol; and (2) the decrease in heart rate as a result of {beta}-blockade was enhanced. Refeeding hypertension in the dietary obese rat may be a potential animal model for some forms of human obesity-related hypertension.

  8. Human heme oxygenase-1 gene transfer lowers blood pressure and promotes growth in spontaneously hypertensive rats.

    PubMed

    Sabaawy, H E; Zhang, F; Nguyen, X; ElHosseiny, A; Nasjletti, A; Schwartzman, M; Dennery, P; Kappas, A; Abraham, N G

    2001-08-01

    Heme oxygenase (HO) catalyzes the conversion of heme to biliverdin, with release of free iron and carbon monoxide. Both heme and carbon monoxide have been implicated in the regulation of vascular tone. A retroviral vector containing human HO-1 cDNA (LSN-HHO-1) was constructed and subjected to purification and concentration of the viral particles to achieve 5x10(9) to 1x10(10) colony-forming units per milliliter. The ability of concentrated infectious viral particles to express human HO-1 (HHO-1) in vivo was tested. A single intracardiac injection of the concentrated infectious viral particles (expressing HHO-1) to 5-day-old spontaneously hypertensive rats resulted in functional expression of the HHO-1 gene and attenuation of the development of hypertension. Rats expressing HHO-1 showed a significant decrease in urinary excretion of a vasoconstrictor arachidonic acid metabolite and a reduction in myogenic responses to increased intraluminal pressure in isolated arterioles. Unexpectedly, HHO-1 chimeric rats showed a simultaneous significant proportionate increase in somatic growth. Thus, delivery of HHO-1 gene by retroviral vector attenuates the development of hypertension and promotes body growth in spontaneously hypertensive rats. PMID:11509478

  9. Risk Factors in Adolescent Hypertension.

    PubMed

    Ewald, D Rose; Haldeman PhD, Lauren A

    2016-01-01

    Hypertension is a complex and multifaceted disease, with many contributing factors. While diet and nutrition are important influences, the confounding effects of overweight and obesity, metabolic and genetic factors, racial and ethnic predispositions, socioeconomic status, cultural influences, growth rate, and pubertal stage have even more influence and make diagnosis quite challenging. The prevalence of hypertension in adolescents far exceeds the numbers who have been diagnosed; studies have found that 75% or more go undiagnosed. This literature review summarizes the challenges of blood pressure classification in adolescents, discusses the impact of these confounding influences, and identifies actions that will improve diagnosis and treatment outcomes. PMID:27335997

  10. Risk Factors in Adolescent Hypertension

    PubMed Central

    Ewald, D. Rose; Haldeman, Lauren A.

    2016-01-01

    Hypertension is a complex and multifaceted disease, with many contributing factors. While diet and nutrition are important influences, the confounding effects of overweight and obesity, metabolic and genetic factors, racial and ethnic predispositions, socioeconomic status, cultural influences, growth rate, and pubertal stage have even more influence and make diagnosis quite challenging. The prevalence of hypertension in adolescents far exceeds the numbers who have been diagnosed; studies have found that 75% or more go undiagnosed. This literature review summarizes the challenges of blood pressure classification in adolescents, discusses the impact of these confounding influences, and identifies actions that will improve diagnosis and treatment outcomes. PMID:27335997

  11. Chopping-Wheel Optical Attenuator

    NASA Technical Reports Server (NTRS)

    Leviton, Douglas B.

    1988-01-01

    Star-shaped rotating chopping wheel provides adjustable time-averaged attenuation of narrow beam of light without changing length of optical path or spectral distribution of light. Duty cycle or attenuation factor of chopped beam controlled by adjusting radius at which beam intersects wheel. Attenuation factor independent of wavelength. Useful in systems in which chopping frequency above frequency-response limits of photodetectors receiving chopped light. Used in systems using synchronous detection with lock-in amplifiers.

  12. Ultrasonic Attenuation in Zircaloy-4

    SciTech Connect

    Gomez, M.P.; Banchik, A.D.; Lopez Pumarega, M.I.; Ruzzante, J.E.

    2005-04-09

    In this work the relationship between Zircaloy-4 grain size and ultrasonic attenuation behavior was studied for longitudinal waves in the frequency range of 10-90 MHz. The attenuation was analyzed as a function of frequency for samples with different mechanical and heat treatments having recrystallized and Widmanstatten structures with different grain size. The attenuation behavior was analyzed by different scattering models, depending on grain size, wavelength and frequency.

  13. Pulmonary arterial hypertension and chronic thromboembolic pulmonary hypertension: pathophysiology.

    PubMed

    Humbert, M

    2010-03-01

    Pulmonary arterial hypertension (PAH) and chronic thromboembolic pulmonary hypertension (CTEPH) are two of the key subgroups of pulmonary hypertension. They are characterised by different risk factors. PAH can be associated with mutations in the gene encoding bone morphogenetic protein receptor type II (BMPR2), HIV infection, congenital heart disease, connective tissue disease (such as systemic sclerosis), and exposure to particular drugs and toxins including fenfluramine derivatives. In contrast, CTEPH can be associated with anti-phospholipid antibodies, splenectomy and the presence of a ventriculo-atrial shunt or an infected pacemaker. The first-line therapies used to treat PAH and CTEPH also differ. While medical therapy tends to be used for patients with PAH, pulmonary endarterectomy is the treatment of choice for patients with CTEPH. However, there are possible common mechanisms behind the two diseases, including endothelial cell dysfunction and distal pulmonary artery remodelling. Further research into these similarities is needed to assist the development of targeted pharmacological therapies for patients with inoperable CTEPH and patients who have persistent pulmonary hypertension after endarterectomy. PMID:20956167

  14. Hypertension: Strengths and limitations of the JNC 8 hypertension guidelines.

    PubMed

    Mancia, Giuseppe

    2014-04-01

    The Eighth Joint National Committee (JNC 8) guidelines on hypertension have generated great interest among physicians. These guidelines differ from those published in 2003 (the JNC 7) - in the document format, blood-pressure cut-off values, and recommendations for antihypertensive drug use. The JNC 8 have some limitations that could affect clinical practice. PMID:24514021

  15. Renovascular hypertension: Pathophysiology, diagnosis, and treatment

    SciTech Connect

    Glorioso, N.; Laragh, J.H.; Rappelli, A.

    1987-01-01

    This book contains 42 selections. Some of the titles are: Clinical Pharmacology of Two Synthetic Atrial Natriuretics Peptides; Reflex Control of Renin Release in Normotensive and Hypertensive Humans; Renal Blood flow in Renovascular Hypertension; and Radioisotopic Studies in Renovascular Hypertension Before and After Surgery or Percutaneous Transluminal Renal Angioplasty.

  16. LINE-ABOVE-GROUND ATTENUATOR

    DOEpatents

    Wilds, R.B.; Ames, J.R.

    1957-09-24

    The line-above-ground attenuator provides a continuously variable microwave attenuator for a coaxial line that is capable of high attenuation and low insertion loss. The device consists of a short section of the line-above- ground plane type transmission lime, a pair of identical rectangular slabs of lossy material like polytron, whose longitudinal axes are parallel to and indentically spaced away from either side of the line, and a geared mechanism to adjust amd maintain this spaced relationship. This device permits optimum fineness and accuracy of attenuator control which heretofore has been difficult to achieve.

  17. An attenuated philosophical gentleman.

    PubMed

    Christie, John R R

    2014-06-20

    Dr. Joseph Black had at one time, a house near us to the west. He was a striking and beautiful person; tall, very thin, and cadaverously pale; his hair carefully powdered, though there was little of it except what was collected in a long thin queue; his eyes dark, clear and large, like deep pools of pure water. He wore black speckless clothes, silk stockings, silver buckles, and either a slim green umbrella, or a genteel brown cane. The general frame and air were feeble and slender. The wildest boy respected Black. No lad could be irreverent toward a man so pale, so gentle, so elegant and so illustrious. So he glided, like a spirit, through our rather mischievous sportiveness, unharmed. He died seated, with a bowl of milk upon his knee, of which his ceasing to be did not spill a drop; a departure which it seemed, after the event, might have been foretold of this attenuated philosophical gentleman. PMID:24921110

  18. Fiber optic attenuator

    NASA Technical Reports Server (NTRS)

    Buzzetti, Mike F. (Inventor)

    1994-01-01

    A fiber optic attenuator of the invention is a mandrel structure through which a bundle of optical fibers is wrapped around in a complete circle. The mandrel structure includes a flexible cylindrical sheath through which the bundle passes. A set screw on the mandrel structure impacts one side of the sheath against two posts on the opposite side of the sheath. By rotating the screw, the sheath is deformed to extend partially between the two posts, bending the fiber optic bundle to a small radius controlled by rotating the set screw. Bending the fiber optic bundle to a small radius causes light in each optical fiber to be lost in the cladding, the amount depending upon the radius about which the bundle is bent.

  19. Effects of Long-term Blockade of Vasopressin Receptor Types 1a and 2 on Cardiac and Renal Damage in a Rat Model of Hypertensive Heart Failure.

    PubMed

    Ikeda, Tomoyuki; Iwanaga, Yoshitaka; Watanabe, Heitaro; Morooka, Hanako; Akahoshi, Yasumitsu; Fujiki, Hiroyuki; Miyazaki, Shunichi

    2015-11-01

    The effects of chronic blockade of vasopressin type 1a receptors (V1aR) and the additive effects of a type 2 receptor (V2R) antagonist on the treatment of hypertension-induced heart failure and renal injury remain to be unknown. In this study, Dahl salt-sensitive hypertensive rats were chronically treated with a vehicle (CONT), a V1aR antagonist (OPC21268; OPC), a V2R antagonist (tolvaptan; TOLV), or a combination of OPC21268 and tolvaptan (OPC/TOLV) from the pre-hypertrophic stage (6 weeks). No treatment altered blood pressure during the study. Significant improvements were seen in median survival for the OPC and TOLV, and the OPC/TOLV showed a further improvement in Kaplan-Meier analysis. Echocardiography showed suppressed left ventricular hypertrophy in the OPC and OPC/TOLV at 11 weeks with improved function in all treatment groups by 17 weeks. In all treatment groups, improvements were seen in the following: myocardial histological changes, creatinine clearance, urinary albumin excretion, and renal histopathologic damage. Also, key mRNA levels were suppressed (eg, endothelin-1 and collagen). In conclusion, chronic V1aR blockade ameliorated disease progression in this rat model, with additive benefits from the combination of V1aR and V2R antagonists. It was associated with protection of both myocardial and renal damage, independent of blood pressure. PMID:26248278

  20. [PREDICTORS OF RESISTANT ARTERIAL HYPERTENSION].

    PubMed

    Lazutkina, A Y; Gorbunov, V V

    2016-01-01

    The paper reports results of 6 year prospective observation of 7959 members of locomotive crews engaged at the Transbaikal Railways. The study aimed to estimate the probability and time of development of resistant arterial hypertension under effect of predictors of this disease. The data obtained are of value for diagnostic, prophylactic, and therapeutic practice. PMID:27522725

  1. Carbamazepine-induced hypertension: A rare case

    PubMed Central

    Kharb, Preeti; Mittal, Niti; Gupta, Mahesh C.

    2015-01-01

    A 74-year-old female with trigeminal neuralgia developed hypertension after the initiation of carbamazepine therapy. The time sequence of start of the suspected drug and onset of hypertension are consistent with the diagnosis. The hypertension did not resolve with antihypertensive therapy or dose reduction of carbamazepine. Patient recovered after the carbamazepine therapy was discontinued. The positive rechallenge and positive dechallenge showed association of carbamazepine therapy with hypertension as its adverse effect. This is a rare case that we report of carbamazepine-induced hypertension and this report may act as alerting mechanism to the health care professionals especially neurologists. PMID:26816475

  2. Cardiovascular magnetic resonance in systemic hypertension

    PubMed Central

    2012-01-01

    Systemic hypertension is a highly prevalent potentially modifiable cardiovascular risk factor. Imaging plays an important role in the diagnosis of underlying causes for hypertension, in assessing cardiovascular complications of hypertension, and in understanding the pathophysiology of the disease process. Cardiovascular magnetic resonance (CMR) provides accurate and reproducible measures of ventricular volumes, mass, function and haemodynamics as well as uniquely allowing tissue characterization of diffuse and focal fibrosis. In addition, CMR is well suited for exclusion of common secondary causes for hypertension. We review the current and emerging clinical and research applications of CMR in hypertension. PMID:22559053

  3. Inhibition of inflammation and fibrosis by a complement C5a receptor antagonist in DOCA-salt hypertensive rats.

    PubMed

    Iyer, Abishek; Woodruff, Trent M; Wu, Mike C L; Stylianou, Con; Reid, Robert C; Fairlie, David P; Taylor, Stephen M; Brown, Lindsay

    2011-11-01

    The anaphylatoxin C5a generated by activation of the innate immunity complement system is a potent inflammatory peptide mediator through the G-protein-coupled receptor C5aR (CD88) present in immune-inflammatory cells, including monocytes, macrophages, neutrophils, T cells, and mast cells. Inflammatory cells infiltrate and initiate the development of fibrosis in the chronically hypertensive heart. In this study, we have investigated whether treatment with a selective C5aR antagonist prevents cardiovascular remodeling in deoxycorticosterone acetate (DOCA)-salt hypertensive rats. Control and DOCA-salt rats were treated with PMX53 (AcF-[OPdChaWR], 1 mg·kg·d oral gavage) for 32 days; structural and functional changes in cardiovascular system were determined. DOCA-salt hypertension increased leukocyte extravasation into ventricular tissue, increasing collagen deposition and ventricular stiffness; PMX53 treatment attenuated these changes, thereby improving cardiac function. Further, treatment with PMX53 suppressed an increased expression of C5aR in the left ventricle from DOCA-salt rats, consistent with the reduced infiltration of inflammatory cells. Vascular endothelial dysfunction in thoracic aortic rings was attenuated by PMX53 treatment, but systolic blood pressure was unchanged in DOCA-salt rats. In the heart, PMX53 treatment attenuated inflammatory cell infiltration, fibrosis, and ventricular stiffness, indicating that C5aR is critically involved in ventricular remodeling by regulating inflammatory responses in the hypertensive heart. PMID:21753735

  4. Purinergic dysregulation in pulmonary hypertension.

    PubMed

    Visovatti, Scott H; Hyman, Matthew C; Goonewardena, Sascha N; Anyanwu, Anuli C; Kanthi, Yogendra; Robichaud, Patrick; Wang, Jintao; Petrovic-Djergovic, Danica; Rattan, Rahul; Burant, Charles F; Pinsky, David J

    2016-07-01

    Despite the fact that nucleotides and adenosine help regulate vascular tone through purinergic signaling pathways, little is known regarding their contributions to the pathobiology of pulmonary arterial hypertension, a condition characterized by elevated pulmonary vascular resistance and remodeling. Even less is known about the potential role that alterations in CD39 (ENTPD1), the ectonucleotidase responsible for the conversion of the nucleotides ATP and ADP to AMP, may play in pulmonary arterial hypertension. In this study we identified decreased CD39 expression on the pulmonary endothelium of patients with idiopathic pulmonary arterial hypertension. We next determined the effects of CD39 gene deletion in mice exposed to normoxia or normobaric hypoxia (10% oxygen). Compared with controls, hypoxic CD39(-/-) mice were found to have a markedly elevated ATP-to-adenosine ratio, higher pulmonary arterial pressures, more right ventricular hypertrophy, more arterial medial hypertrophy, and a pro-thrombotic phenotype. In addition, hypoxic CD39(-/-) mice exhibited a marked increase in lung P2X1 receptors. Systemic reconstitution of ATPase and ADPase enzymatic activities through continuous administration of apyrase decreased pulmonary arterial pressures in hypoxic CD39(-/-) mice to levels found in hypoxic CD39(+/+) controls. Treatment with NF279, a potent and selective P2X1 receptor antagonist, lowered pulmonary arterial pressures even further. Our study is the first to implicate decreased CD39 and resultant alterations in circulating purinergic signaling ligands and cognate receptors in the pathobiology of pulmonary arterial hypertension. Reconstitution and receptor blocking experiments suggest that phosphohydrolysis of purinergic nucleotide tri- and diphosphates, or blocking of the P2X1 receptor could serve as treatment for pulmonary arterial hypertension. PMID:27208163

  5. HNF1 AND HYPERTENSIVE NEPHROPATHY

    PubMed Central

    Dmitrieva, Renata I.; Hinojos, Cruz A.; Boerwinkle, Eric; Braun, Michael C.; Fornage, Myriam; Doris, Peter A.

    2009-01-01

    Hypertension in SHR is associated with renal redox stress and we hypothesized that nephropathy arises in SHR-A3 from altered capacity to mitigate redox stress compared with nephropathy-resistant SHR lines. We measured renal expression of redox genes in distinct lines of the spontaneously hypertensive rat (SHR-A3, SHR-B2, SHR-C) and the normotensive WKY strain. The SHR lines differ in either resisting (SHR-B2, SHR-C) or experiencing hypertensive nephropathy (SHR-A3). Immediately prior to the emergence of hypertensive renal injury expression of redox genes in SHR-A3 was profoundly altered compared with the injury-resistant SHR lines and WKY. This change appeared to arise in anti-oxidant genes where 16 of 28 were expressed at 34.3% of the level in the reference strain (WKY). No such change was observed in the injury-resistant SHR lines. We analyzed occurrence of transcription factor matrices (TFM) in the promoters of the down-regulated antioxidant genes. In these genes, the HNF1 TFM was found to be nearly twice as likely to be present and the overall frequency of HNF1 sites was nearly 5 times higher, compared with HNF1 TFMs in anti-oxidant genes that were not down-regulated. We identified 35 other (non-redox) renal genes regulated by HNF1. These were also significantly down-regulated in SHR-A3, but not in SHR-B2 or SHR-C. Finally, expression of genes that comprise HNF1 (Tcf1, Tcf2 and Dcoh) was also down-regulated in SHR-A3. The present experiments uncover a major change in transcriptional control by HNF1 that affects redox and other genes and precedes emergence of hypertensive renal injury. PMID:18443232

  6. Contribution of Kv7 channels to natriuretic peptide mediated vasodilation in normal and hypertensive rats.

    PubMed

    Stott, Jennifer B; Barrese, Vincenzo; Jepps, Thomas A; Leighton, Emma V; Greenwood, Iain A

    2015-03-01

    The Kv7 family of voltage-gated potassium channels are expressed within the vasculature where they are key regulators of vascular tone and mediate cAMP-linked endogenous vasodilator responses, a pathway that is compromised in hypertension. However, the role of Kv7 channels in non-cAMP-linked vasodilator pathways has not been investigated. Natriuretic peptides are potent vasodilators, which operate primarily through the activation of a cGMP-dependent signaling pathway. This study investigated the putative role of Kv7 channels in natriuretic peptide-dependent relaxations in the vasculature of normal and hypertensive animals. Relaxant responses of rat aorta to both atrial and C-type natriuretic peptides and the nitric oxide donor sodium nitroprusside were impaired by the Kv7 blocker linopirdine (10 μmol/L) but not by the Kv7.1-specific blocker HMR1556 (10 μmol/L) and other K(+) channel blockers. In contrast, only the atrial natriuretic peptide response was sensitive to linopirdine in the renal artery. These Kv7-mediated responses were attenuated in arteries from hypertensive rats. Quantitative polymerase chain reaction showed that A- and B-type natriuretic peptide receptors were expressed at high levels in the aorta and renal artery from normal and spontaneously hypertensive rats. This study provides the first evidence that natriuretic peptide responses are impaired in hypertension and that recruitment of Kv7 channels is a key component of natriuretic peptide-dependent vasodilations. PMID:25547342

  7. Magnetic Resonance Imaging in Pediatric Pulmonary Hypertension

    PubMed Central

    Olgunturk, Rana; Cevik, Ayhan; Terlemez, Semiha; Kacar, Emre; Oner, Yusuf Ali

    2015-01-01

    The present study aims to determine the efficacy and reliability of cardiovascular magnetic resonance imaging in establishing the diagnosis and prognosis of pulmonary hypertension in children. This is a retrospective comparison of 25 children with pulmonary hypertension and a control group comprising 19 healthy children. The diagnosis of pulmonary hypertension was made when the mean pulmonary artery pressure was ≥25 mmHg by catheter angiography. The children with pulmonary hypertension had significantly lower body mass indices than did the healthy children (P=0.048). In addition, the children with pulmonary hypertension had significantly larger main pulmonary artery diameters and ascending aortic diameters (both P=0.001) but statistically similar ratios of main pulmonary artery diameter-to-ascending aortic diameter. If the main pulmonary artery diameter was ≥25 mm, pediatric pulmonary hypertension was diagnosed with 72% sensitivity and 84% specificity. In the event that the ratio of main pulmonary artery diameter-to-ascending aorta diameter was ≥1, pediatric pulmonary hypertension was diagnosed with 60% sensitivity and 53% specificity. When compared with children who had New York Heart Association functional class II pulmonary hypertension, the children with functional class III pulmonary hypertension had significantly larger main (P=0.046), right (P=0.036), and left (P=0.003) pulmonary arteries. Cardiovascular magnetic resonance imaging is useful in the diagnosis of children with pulmonary hypertension. Pediatric pulmonary hypertension can be diagnosed with high sensitivity and specificity when the main pulmonary artery diameter measures ≥25 mm. PMID:26175631

  8. Magnetic resonance imaging in pediatric pulmonary hypertension.

    PubMed

    Pektas, Ayhan; Olgunturk, Rana; Cevik, Ayhan; Terlemez, Semiha; Kacar, Emre; Oner, Yusuf Ali

    2015-06-01

    The present study aims to determine the efficacy and reliability of cardiovascular magnetic resonance imaging in establishing the diagnosis and prognosis of pulmonary hypertension in children. This is a retrospective comparison of 25 children with pulmonary hypertension and a control group comprising 19 healthy children. The diagnosis of pulmonary hypertension was made when the mean pulmonary artery pressure was ≥25 mmHg by catheter angiography. The children with pulmonary hypertension had significantly lower body mass indices than did the healthy children (P=0.048). In addition, the children with pulmonary hypertension had significantly larger main pulmonary artery diameters and ascending aortic diameters (both P=0.001) but statistically similar ratios of main pulmonary artery diameter-to-ascending aortic diameter. If the main pulmonary artery diameter was ≥25 mm, pediatric pulmonary hypertension was diagnosed with 72% sensitivity and 84% specificity. In the event that the ratio of main pulmonary artery diameter-to-ascending aorta diameter was ≥1, pediatric pulmonary hypertension was diagnosed with 60% sensitivity and 53% specificity. When compared with children who had New York Heart Association functional class II pulmonary hypertension, the children with functional class III pulmonary hypertension had significantly larger main (P=0.046), right (P=0.036), and left (P=0.003) pulmonary arteries. Cardiovascular magnetic resonance imaging is useful in the diagnosis of children with pulmonary hypertension. Pediatric pulmonary hypertension can be diagnosed with high sensitivity and specificity when the main pulmonary artery diameter measures ≥25 mm. PMID:26175631

  9. Range Restriction and Attenuation Corrections.

    ERIC Educational Resources Information Center

    Mumford, Michael D.; Mendoza, Jorge L.

    The present paper reviews the techniques commonly used to correct an observed correlation coefficient for the simultaneous influence of attenuation and range restriction effects. It is noted that the procedure which is currently in use may be somewhat biased because it treats range restriction and attenuation as independent restrictive influences.…

  10. Suicide Risk: Amplifiers and Attenuators.

    ERIC Educational Resources Information Center

    Plutchik, Robert; Van Praag, Herman M.

    1994-01-01

    Attempts to integrate findings on correlates of suicide and violent risk in terms of a theory called a two-stage model of countervailing forces, which assumes that the strength of aggressive impulses is modified by amplifiers and attenuators. The vectorial interaction of amplifiers and attenuators creates an unstable equilibrium making prediction…

  11. Adjustable Optical-Fiber Attenuator

    NASA Technical Reports Server (NTRS)

    Buzzetti, Mike F.

    1994-01-01

    Adjustable fiber-optic attenuator utilizes bending loss to reduce strength of light transmitted along it. Attenuator functions without introducing measurable back-reflection or insertion loss. Relatively insensitive to vibration and changes in temperature. Potential applications include cable television, telephone networks, other signal-distribution networks, and laboratory instrumentation.

  12. The diagnosis and management of hypertensive crises.

    PubMed

    Varon, J; Marik, P E

    2000-07-01

    Severe hypertension is a common clinical problem in the United States, encountered in various clinical settings. Although various terms have been applied to severe hypertension, such as hypertensive crises, emergencies, or urgencies, they are all characterized by acute elevations in BP that may be associated with end-organ damage (hypertensive crisis). The immediate reduction of BP is only required in patients with acute end-organ damage. Hypertension associated with cerebral infarction or intracerebral hemorrhage only rarely requires treatment. While nitroprusside is commonly used to treat severe hypertension, it is an extremely toxic drug that should only be used in rare circumstances. Furthermore, the short-acting calcium channel blocker nifedipine is associated with significant morbidity and should be avoided. Today, a wide range of pharmacologic alternatives are available to the practitioner to control severe hypertension. This article reviews some of the current concepts and common misconceptions in the management of patients with acutely elevated BP. PMID:10893382

  13. Tongxinluo Protects against Hypertensive Kidney Injury in Spontaneously-Hypertensive Rats by Inhibiting Oxidative Stress and Activating Forkhead Box O1 Signaling

    PubMed Central

    Luo, Wei-min; Kong, Jing; Gong, Yan; Liu, Xiao-qiong; Yang, Rui-xue; Zhao, Yu-xia

    2015-01-01

    Hypertension is an independent risk factor for the progression of chronic renal failure, and oxidative stress plays a critical role in hypertensive renal damage. Forkbox O1(FoxO1) signaling protects cells against oxidative stress and may be a useful target for treating oxidative stress-induced hypertension. Tongxinluo is a traditional Chinese medicine with cardioprotective and renoprotective functions. Therefore, this study aimed to determine the effects of Tongxinluo in hypertensive renal damage in spontaneously hypertensive rats(SHRs)and elucidate the possible involvement of oxidative stress and FoxO1 signaling in its molecular mechanisms. SHRs treated with Tongxinluo for 12 weeks showed a reduction in systolic blood pressure. In addition to increasing creatinine clearance, Tongxinluo decreased urinary albumin excretion, oxidative stress injury markers including malondialdehyde and protein carbonyls, and expression of nicotinamide adenine dinucleotide phosphate oxidase subunits and its activity in SHR kidneys. While decreasing phosphorylation of FoxO1, Tongxinluo also inhibited the phosphorylation of extracellular signal-regulated kinase1/2 and p38 and enhanced manganese superoxide dismutase and catalase activities in SHR kidneys. Furthermore, histology revealed attenuation of glomerulosclerosis and renal podocyte injury, while Tongxinluo decreased the expression of α-smooth muscle actin, extracellular matrixprotein, transforming growth factor β1 and small mothers against decapentaplegic homolog 3,and improved tubulointerstitial fibrosis in SHR kidneys. Finally, Tongxinluo inhibited inflammatory cell infiltration as well as expression of tumor necrosis factor-α and interleukin-6. In conclusion, Tongxinluo protected SHRs against hypertension-induced renal injury by exerting antioxidant, antifibrotic, and anti-inflammatory activities. Moreover, the underlying mechanisms of these effects may involve inhibition of oxidative stress and functional activation of Fox

  14. [Hypertensive crises in patients with arterial hypertension in ambulatory treatment].

    PubMed

    Gomes Guedes, Nirla; Chaves Costa, Francisca Bertilia; Moreira, Rafaella Pessoa; Moreira, Tahissa Frota; Soares Chavess, Emilia; de Araújo, Thelma Leite

    2005-06-01

    This study assessed the sociodemographic characteristics and the characteristics of therapeutic adhesion of 27 bearers of arterial hypertension undergoing ambulatorial treatment who had hypertensive urgencies crises or emergencies in the city of Fortaleza in the period between October of 2002 and May of 2003. The majority were women, between 50 and 60-years old, with little formal education, treatment time shorter than 5 years and time of diagnosis varying from 5 to 10 years. The use of medicine was the treatment that was most mentioned, followed by the reduction of the consumption of salt and attendance to medical appointments. However, attending the appointments and receiving orientation did not seem to change their behavior, since most of the patients that were interviewed practiced no physical exercises and demonstrated little knowledge of the illness, for they attributed the rise of the arterial pressure to emotional factors. PMID:16060305

  15. Structural and functional vascular alterations and incident hypertension in normotensive adults: the Multi-Ethnic Study of Atherosclerosis.

    PubMed

    Peralta, Carmen A; Adeney, Kathryn L; Shlipak, Michael G; Jacobs, David; Duprez, Daniel; Bluemke, David; Polak, Joseph; Psaty, Bruce; Kestenbaum, Bryan R

    2010-01-01

    Vascular abnormalities may exist before clinical hypertension. Using Poisson regression, the authors studied the association of coronary artery calcium (CAC), common carotid intima-media thickness (CIMT), aortic distensibility, and large and small arterial elasticity with incident hypertension among 2,512 normotensive US adults free of cardiovascular disease. Incidence rate ratios for incident hypertension (blood pressure > or =140/90 mm Hg or new antihypertensive medication) were calculated. Increased CAC was associated with incident hypertension in demographics-adjusted models (incidence rate ratio (IRR) = 1.35, 95% confidence interval (CI): 1.04, 1.75; IRR = 1.35, 95% CI: 1.02, 1.78; and IRR = 1.59, 95% CI: 1.12, 2.25 for CAC scores of 30-99, 100-399, and > or =400, respectively) but was attenuated after further adjustment. Increased common CIMT was associated with incident hypertension (IRR = 1.77, 95% CI: 1.28, 2.46 for quintile 4; IRR = 1.80, 95% CI: 1.28, 2.53 for quintile 5). Participants with the lowest, compared with the highest, aortic distensibility had an increased risk of hypertension (IRR = 1.75, 95% CI: 1.10, 2.79), as did those with the lowest large arterial elasticity (IRR = 1.49, 95% CI: 1.11, 1.99). Lower small arterial elasticity was incrementally associated with incident hypertension starting at quintile 2 (IRR = 2.01, 95% CI: 1.39, 2.91; IRR = 2.47, 95% CI: 1.71, 3.57; IRR = 2.73, 95% CI: 1.88, 3.95; and IRR = 2.85, 95% CI: 1.95, 4.16). Structural and functional vascular abnormalities are independent predictors of incident hypertension. These findings are important for understanding the pathogenesis of hypertension. PMID:19951938

  16. Differential effects of complement activation products c3a and c5a on cardiovascular function in hypertensive pregnant rats.

    PubMed

    Lillegard, Kathryn E; Loeks-Johnson, Alex C; Opacich, Jonathan W; Peterson, Jenna M; Bauer, Ashley J; Elmquist, Barbara J; Regal, Ronald R; Gilbert, Jeffrey S; Regal, Jean F

    2014-11-01

    Early-onset pre-eclampsia is characterized by decreased placental perfusion, new-onset hypertension, angiogenic imbalance, and endothelial dysfunction associated with excessive activation of the innate immune complement system. Although our previous studies demonstrated that inhibition of complement activation attenuates placental ischemia-induced hypertension using the rat reduced uterine perfusion pressure (RUPP) model, the important product(s) of complement activation has yet to be identified. We hypothesized that antagonism of receptors for complement activation products C3a and C5a would improve vascular function and attenuate RUPP hypertension. On gestational day (GD) 14, rats underwent sham surgery or vascular clip placement on ovarian arteries and abdominal aorta (RUPP). Rats were treated once daily with the C5a receptor antagonist (C5aRA), PMX51 (acetyl-F-[Orn-P-(D-Cha)-WR]), the C3a receptor antagonist (C3aRA), SB290157 (N(2)-[(2,2-diphenylethoxy)acetyl]-l-arginine), or vehicle from GD 14-18. Both the C3aRA and C5aRA attenuated placental ischemia-induced hypertension without affecting the decreased fetal weight or decreased concentration of free circulating vascular endothelial growth factor (VEGF) also present in this model. The C5aRA, but not the C3aRA, attenuated placental ischemia-induced increase in heart rate and impaired endothelial-dependent relaxation. The C3aRA abrogated the acute pressor response to C3a peptide injection, but it also unexpectedly attenuated the placental ischemia-induced increase in C3a, suggesting nonreceptor-mediated effects. Overall, these results indicate that both C3a and C5a are important products of complement activation that mediate the hypertension regardless of the reduction in free plasma VEGF. The mechanism by which C3a contributes to placental ischemia-induced hypertension appears to be distinct from that of C5a, and management of pregnancy-induced hypertension is likely to require a broad anti

  17. Hypertensive urgency: an important aetiology of rebound hypertension.

    PubMed

    Malaty, John; Malaty, Irene A

    2014-01-01

    A 46-year-old African-American man with a history of hypertension, end-stage kidney disease (on haemodialysis) and previous cocaine misuse presented to the emergency room with a sudden onset of severe headache and diaphoresis without other neurological or cardiovascular signs/symptoms. He checked his blood pressure at home and found it to be 230/130. It did not improve despite taking two serial doses of oral clonidine 0.3 mg. Evaluation with head CT and lumbar puncture demonstrated no acute intracranial process, such as subarachnoid haemorrhage. These symptoms started after he took Libido-Max, an over-the-counter supplement for erectile dysfunction. This supplement includes yohimbine, an α-2 antagonist, which counteracts the effects of oral clonidine, one of his routine antihypertensive medications. This led to rebound hypertension and made his hypertensive urgency resistant to oral clonidine. He was successfully treated with intravenous labetalol and his symptoms quickly resolved after lowering of his blood pressure. PMID:25336552

  18. Chronotherapy with conventional blood pressure medications improves management of hypertension and reduces cardiovascular and stroke risks.

    PubMed

    Hermida, Ramón C; Ayala, Diana E; Smolensky, Michael H; Fernández, José R; Mojón, Artemio; Portaluppi, Francesco

    2016-05-01

    Correlation between blood pressure (BP) and target organ damage, vascular risk and long-term patient prognosis is greater for measurements derived from around-the-clock ambulatory BP monitoring than in-clinic daytime ones. Numerous studies consistently substantiate the asleep BP mean is both an independent and a much better predictor of cardiovascular disease (CVD) risk than either the awake or 24 h means. Sleep-time hypertension is much more prevalent than suspected, not only in patients with sleep disorders, but also among those who are elderly or have type 2 diabetes, chronic kidney disease or resistant hypertension. Hence, cost-effective adequate control of sleep-time BP is of marked clinical relevance. Ingestion time, according to circadian rhythms, of hypertension medications of six different classes and their combinations significantly affects BP control, particularly sleep-time BP, and adverse effects. For example, because the high-amplitude circadian rhythm of the renin-angiotensin-aldosterone system activates during nighttime sleep, bedtime vs. morning ingestion of angiotensin-converting enzyme inhibitors and angiotensin receptor blockers better reduces the asleep BP mean, with additional benefit, independent of medication terminal half-life, of converting the 24 h BP profile into more normal dipper patterning. The MAPEC (Monitorización Ambulatoria para Predicción de Eventos Cardiovasculares) study, first prospective randomized treatment-time investigation designed to test the worthiness of bedtime chronotherapy with ⩾1 conventional hypertension medications so as to specifically target attenuation of asleep BP, demonstrated, relative to conventional morning therapy, 61% reduction of total CVD events and 67% decrease of major CVD events, that is, CVD death, myocardial infarction, and ischemic and hemorrhagic stroke. The MAPEC study, along with other earlier conducted less refined trials, documents the asleep BP mean is the most significant

  19. Attenuation of Vaccinia Virus.

    PubMed

    Yakubitskiy, S N; Kolosova, I V; Maksyutov, R A; Shchelkunov, S N

    2015-01-01

    Since 1980, in the post-smallpox vaccination era the human population has become increasingly susceptible compared to a generation ago to not only the variola (smallpox) virus, but also other zoonotic orthopoxviruses. The need for safer vaccines against orthopoxviruses is even greater now. The Lister vaccine strain (LIVP) of vaccinia virus was used as a parental virus for generating a recombinant 1421ABJCN clone defective in five virulence genes encoding hemagglutinin (A56R), the IFN-γ-binding protein (B8R), thymidine kinase (J2R), the complement-binding protein (C3L), and the Bcl-2-like inhibitor of apoptosis (N1L). We found that disruption of these loci does not affect replication in mammalian cell cultures. The isogenic recombinant strain 1421ABJCN exhibits a reduced inflammatory response and attenuated neurovirulence relative to LIVP. Virus titers of 1421ABJCN were 3 lg lower versus the parent VACV LIVP when administered by the intracerebral route in new-born mice. In a subcutaneous mouse model, 1421ABJCN displayed levels of VACV-neutralizing antibodies comparable to those of LIVP and conferred protective immunity against lethal challenge by the ectromelia virus. The VACV mutant holds promise as a safe live vaccine strain for preventing smallpox and other orthopoxvirus infections. PMID:26798498

  20. Emergency Management of Hypertension in Children

    PubMed Central

    Singh, Dinesh; Akingbola, Olugbenga; Yosypiv, Ihor; El-Dahr, Samir

    2012-01-01

    Systemic arterial hypertension in children has traditionally been thought to be secondary in origin. Increased incidence of risk factors like obesity, sedentary life-styles, and faulty dietary habits has led to increased prevalence of the primary arterial hypertension (PAH), particularly in adolescent age children. PAH has become a global epidemic worldwide imposing huge economic constraint on health care. Sudden acute increase in systolic and diastolic blood pressure can lead to hypertensive crisis. While it generally pertains to secondary hypertension, occurrence of hypertensive crisis in PAH is however rare in children. Hypertensive crisis has been further subclassified depending on presence or absence of end-organ damage into hypertensive emergency or urgency. Both hypertensive emergencies and urgencies are known to cause significant morbidity and mortality. Increasing awareness among the physicians, targeted at investigation of the pathophysiology of hypertension and its complications, better screening methods, generation, and implementation of novel treatment modalities will impact overall outcomes. In this paper, we discuss the etiology, pathogenesis, and management of hypertensive crisis in children. An extensive database search using keywords was done to obtain the information. PMID:22577545