scholarly journals Superoxide Mediates Depressive Effects Induced by Hydrogen Sulfide in Rostral Ventrolateral Medulla of Spontaneously Hypertensive Rats

2015 ◽  
Vol 2015 ◽  
pp. 1-8 ◽  
Author(s):  
Haiyun Yu ◽  
Haiyan Xu ◽  
Xiaoni Liu ◽  
Nana Zhang ◽  
Anqi He ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Blood Pressure ◽  
Hydrogen Sulfide ◽  
Nadph Oxidase ◽  
Spontaneously Hypertensive Rats ◽  
Ventrolateral Medulla ◽  
Ros Production ◽  
Hypertensive Rats ◽  
Spontaneously Hypertensive ◽  
Nadph Oxidase Activity

Hydrogen sulfide (H2S) plays a crucial role in the regulation of blood pressure and oxidative stress. In the present study, we tested the hypothesis that H2S exerts its cardiovascular effects by reducing oxidative stress via inhibition of NADPH oxidase activity in the rostral ventrolateral medulla (RVLM). We examined cell distributions of cystathionine-β-synthase (CBS) and effects of H2S on reactive oxygen species (ROS) and mean arterial blood pressure (MAP) in spontaneously hypertensive rats (SHRs). We found that CBS was expressed in neurons of the RVLM, and the expression was lower in SHRs than in Wistar-Kyoto rats. Microinjection of NaHS (H2S donor), S-adenosyl-l-methionine (SAM, a CBS agonist), or Apocynin (NADPH oxidase inhibitor) into the RVLM reduced the ROS level, NADPH oxidase activity, and MAP, whereas microinjection of hydroxylamine hydrochloride (HA, a CBS inhibitor) increased MAP. Furthermore, intracerebroventricular infusion of NaHS inhibited phosphorylation ofp47phox, a key step of NADPH oxidase activation. Since decreasing ROS level in the RVLM reduces MAP and heart rate and increasing H2S reduces ROS production, we conclude that H2S exerts an antihypertensive effect via suppressing ROS production. H2S, as an antioxidant, may be a potential target for cardiovascular diseases.

scholarly journals Increased Blood Pressure Causes Lymphatic Endothelial Dysfunction via Oxidative Stress in Spontaneously Hypertensive Rats

Hypertension ◽  
2020 ◽  
Vol 76 (2) ◽  
pp. 598-606
Author(s):  
Masashi Mukohda ◽  
Risuke Mizuno ◽  
Hiroshi Ozaki
Keyword(s):  
Oxidative Stress ◽  
Nitric Oxide ◽  
Blood Pressure ◽  
Endothelial Dysfunction ◽  
Nadph Oxidase ◽  
Sodium Nitroprusside ◽  
P38 Mapk ◽  
Spontaneously Hypertensive Rats ◽  
Hypertensive Rats ◽  
Spontaneously Hypertensive

The lymphatic system is involved in the pathogenesis of edema, inflammation, and cancer metastasis. Because lymph vessels control fluid electrolytes and volume balance, changes in lymphatic activity can be expected to alter systemic blood pressure. This study examined possible changes in lymphatic contractile properties in spontaneously hypertensive rats (SHR). Thoracic ducts isolated from 10- to 12-week-old SHR exhibited either decreased acetylcholine-induced endothelium-dependent relaxation or sodium nitroprusside-induced endothelium-independent relaxation compared with age-matched Wister-Kyoto rats. The impairment in acetylcholine responsiveness was more pronounced than sodium nitroprusside responsiveness. N-Nitro-L-arginine methyl ester, a nitric oxide synthase inhibitor blunted acetylcholine-induced relaxation in Wister-Kyoto rats, indicating an involvement of endothelial nitric oxide production. Endothelial dysfunction in lymph vessels of SHR was attenuated by tempol (a superoxide dismutase mimetic), apocynin, or VAS-2870 (NADPH oxidase inhibitors). Consistent with these observations, nitrotyrosine levels were significantly elevated in SHR, indicative of increased oxidative stress. In addition, protein expression of NADPH oxidase 2 and phosphorylation of p47 phox (Ser345) were significantly increased in SHR. Further, SB203580 (a p38 MAPK inhibitor) restored the acetylcholine-induced relaxation in SHR. It is notable that 4-week-old SHR, which exhibited normal blood pressure, did not show any decreased activity of acetylcholine- or sodium nitroprusside-induced relaxation. Additionally, antihypertensive treatment of 4-week-old SHR with hydrochlorothiazide and reserpine or hydrochlorothiazide and hydralazine for 6 weeks completely restored lymphatic endothelial dysfunction. We conclude that contractile activity of lymphatic vessels is functionally impaired with the development of increasing blood pressure, which is mediated through increased oxidative stress via the p38 MAPK/NADPH oxidase 2 pathway.

scholarly journals Combination of Exercise Training and SOD Mimetic Tempol Enhances Upregulation of Nitric Oxide Synthase in the Kidney of Spontaneously Hypertensive Rats

2020 ◽  
Vol 2020 ◽  
pp. 1-10
Author(s):  
Pengyu Cao ◽  
Osamu Ito ◽  
Daisuke Ito ◽  
Rong Rong ◽  
Yang Zheng ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Exercise Training ◽  
Nadph Oxidase ◽  
Oxidase Activity ◽  
Spontaneously Hypertensive Rats ◽  
Hypertensive Rats ◽  
Sod Activity ◽  
Spontaneously Hypertensive ◽  
Nadph Oxidase Activity ◽  
Expression Levels

Both exercise training (Ex) and superoxide dismutase (SOD) mimetic tempol have antihypertensive and renal protective effects in rodent models of several hypertensions. We recently reported that Ex increases nitric oxide (NO) production and the expression levels of endothelial and neuronal NO synthase (eNOS and nNOS) in the kidney and aorta of the spontaneously hypertensive rats (SHR) and normotensive Wistar–Kyoto rats (WKY). We also found that endogenous hydrogen peroxide (H2O2) upregulates the expression levels of eNOS and nNOS in SHR. To elucidate the mechanism of the Ex-upregulated NO system in the kidney, we examined the additive effect of Ex and tempol on the renal NO system in SHR and WKY. Our data showed that, in SHR, both Ex and tempol increase the levels of H2O2 and nitrate/nitrite (NOx) in plasma and urine. We also observed an increased renal NOS activity and upregulated expression levels of eNOS and nNOS with decreased NADPH oxidase activity. The effects of the combination of Ex and tempol on these variables were cumulate in SHR. On the other hand, we found that Ex increases these variables with increased renal NADPH oxidase activity, but tempol did not change these variables or affect the Ex-induced upregulation in the activity and expression of NOS in WKY. The SOD activity in the kidney and aorta was activated by tempol only in SHR, but not in WKY; whereas Ex increased SOD activity only in the aorta in both SHR and WKY. These results indicate that Ex-induced endogenous H2O2 produced in the blood vessel and other organs outside of the kidney may be carried to the kidney by blood flow and stimulates the NO system in the kidney.

Abstract 1378: NFkb Blockade Attenuate Cytokines And Oxidative Stress In The Paraventricular Nucleus And Decreases Neurohumoral Excitation In Spontaneously Hypertensive Rats

Circulation ◽  
2007 ◽  
Vol 116 (suppl_16) ◽  
Author(s):  
Nithya Mariappan ◽  
Carrie Elks ◽  
Masudul Haque ◽  
Philip J Ebnezer ◽  
Elizabeth McIIwain ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Blood Pressure ◽  
Paraventricular Nucleus ◽  
Spontaneously Hypertensive Rats ◽  
Left Ventricular ◽  
Oxidative Stress Markers ◽  
Hypertensive Rats ◽  
Spontaneously Hypertensive ◽  
Stress Markers ◽  
And Oxidative Stress

The transcriptional factor, nuclear factor kappa B (NFkB) plays an important role in the regulation of cytokines. Among the cytokines, tumor necrosis factor-alpha (TNF) plays an important role in cardiovascular pathophysiology. This study was done to determine whether TNF-α blockade with etanercept (ETN) or NFkB blockade with dithiol pyrolidine thiocarbamate (PDTC) attenuate oxidative stress in the paraventricular nucleus (PVN) and contribute to neurohumoral excitation in spontaneously hypertensive rats. Method: Male 20 week old SHR rats were treated with ETN (1 mg/kg BW, sc) or PDTC (100mg/kg BW, ip) for 5 week period. Left ventricular function was measured at baseline (20 weeks) and at 25 weeks using echocardiography. Blood pressure was measured at weekly intervals throughout the study. At the end of the protocol rats were sacrificed the PVN was microdissected for the measurement of cytokines, oxidative stress markers using real time PCR (fold increase compared to WKY controls) and by immunohistochemistry. Superoxide, total reactive oxygen species and peroxynitrite were measured in the PVN and LV using electron paramagnetic resonance. Plasma norepinephrine and epinephrine an indicator of neurohumoral excitation was measured using HPLC-EC. Results: PVN data are tabulated. SHR animals had increased expression of protein and mRNA for cytokines and oxidative stress markers in the PVN and LV with increased MAP and cardiac hypertrophy when compared to WKY rats. Treatment with ETN and PDTC attenuated these increases with PDTC showing marked effect than ETN on hypertrophy and blood pressure responses. Conclusion: These findings suggest that cytokine activation in the PVN contributes to increased oxidative stress and neurohumoral excitation in hypertension.

Abstract P150: Sex Difference of Hypertension in Spontaneously Hypertensive Rats: Role of Mitochondrial Oxidative Stress

Hypertension ◽  
2017 ◽  
Vol 70 (suppl_1) ◽  
Author(s):  
Rodrigo O Maranon ◽  
Carolina Dalmasso ◽  
Chetal N Patil ◽  
Jane F Reckelhoff
Keyword(s):  
Oxidative Stress ◽  
Blood Pressure ◽  
Sex Difference ◽  
Spontaneously Hypertensive Rats ◽  
Pressor Response ◽  
Premenopausal Women ◽  
Hypertensive Rats ◽  
Mitochondrial Oxidative Stress ◽  
Spontaneously Hypertensive ◽  
Mitochondrial Superoxide

Men have higher blood pressure (BP) than premenopausal women. Pressor response to oxidative stress may be a major contributor to the sex difference in BP control. Mitochondrial oxidative stress is associated with hypertension; however, whether mitochondrial oxidative stress plays a role in the sex difference in BP is unknown. In the present study, we tested the hypothesis that mitochondrial oxidative stress contributes to the sex difference in BP regulation in spontaneously hypertensive rats (SHR). Young intact (iYMSHR) and castrated males (cYMSHR), and females SHR (YFSHR) (3 mos of age) were implanted with radiotelemeters, and after a 4 day baseline BP, were treated with mitoTempo (0.75 mg/kg/d, sc minipumps), a specific scavenger of mitochondrial superoxide, for 7 days. Following 10 days washout of mito-tempo, rats were treated with Tempol (30 mg/kg/day, po drinking water) for 7 days. iYMSHR have higher blood pressure (by telemetry) than cYMSHR and YFSHR (148±1 mmHg, n=5, vs 132±1 mmHg, n=5, and 139±1 mmHg, n=5; p<0.01, respectively). MitoTempo reduced BP by 6% in iYMSHR (147±1 vs 139±1, n=5; p<0.05) compared to females (3%: 139±1 vs 136±1; n=5; p: NS) and castrated males (4.5%: 132±1 vs 126±1, n=5; p<0.05). After 10 days washout, tempol reduced BP only in iYMSHR (144±1 vs 130±1 mmHg, n=5; p<0.05). Our results suggest that mitochondrial oxidative stress may contribute to BP regulation in male SHR, but has no effect in females. The data also suggest that the presence of testosterone is necessary for the pressor response to oxidative stress in males since Tempol had no effect on BP in castrated males. Further studies examining the effect of steroid hormones and mitochondria in BP regulation are necessary to elucidate the importance of mitochondrial oxidative stress on sex difference of hypertension.

scholarly journals Effects of Diabetic Hyperglycemia on Central Ang-(1-7)-Mas-R-nNOS Pathways in Spontaneously Hypertensive Rats

2016 ◽  
Vol 40 (5) ◽  
pp. 1186-1197 ◽  
Author(s):  
He Li ◽  
Xian Liu ◽  
Zhongqiao Ren ◽  
Jinxia Gu ◽  
Yingjie Lu ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Blood Pressure ◽  
Cerebral Cortex ◽  
Spontaneously Hypertensive Rats ◽  
Hypertensive Rats ◽  
Systemic Injection ◽  
Spontaneously Hypertensive ◽  
Arterial Blood ◽  
Cerebrovascular Dysfunction ◽  
And Control

Background/Aims: Hypertension is a major cause of stroke, and diabetes can increase incidence of this disease. We determined the role played by central angiotensin-(1-7) [Ang-(1-7)] pathway in modulating spontaneously hypertension with diabetic hyperglycemia. Methods: Western Blot analysis and ELISA were used to determine the protein expression of Ang-(1-7) and its signal pathway Mas-R-nNOS in the cerebral cortex and hippocampus of spontaneously hypertensive rats (SHR) and control animals. In a subset of animals, diabetic hyperglycemia was induced by systemic injection of streptozotocin (STZ). We analyzed a relationship between the levels of central Ang-(1-7) and plasma brain natriuretic peptide (BNP) indicating a risk of ischemic stroke. We further examined the effects of Ang-(1-7) on arterial blood pressure. Results: Our findings demonstrated for the first time that administration of STZ 1) attenuates the levels of Ang-(1-7) in the cerebral cortex and hippocampus, which are closely linked to plasma BNP; and 2) leads to downregulation of central Ang-(1-7)-Mas-R-nNOS pathways. Notably, STZ has greater effects in SHR. Additionally, inhibition of oxidative stress can largely improve downregulation of Ang-(1-7) in diabetic SHR. Moreover, central stimulation of Ang-(1-7) pathway or a blockade of oxidative stress improves systolic blood pressure in diabetic SHR. Conclusions: The Ang-(1-7) signaling pathway is engaged in the adaptive mechanisms associated with diabetic hypertension, suggesting that enhancing Ang-(1-7)-Mas-R-nNOS system is likely to be beneficial in preventing against cardiovascular and cerebrovascular dysfunction and vulnerability related to spontaneously hypertension, particularly to diabetic hypertension.

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