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.

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 Coconut oil supplementation reduces blood pressure and oxidative stress in spontaneously hypertensive rats

2014 ◽  
Vol 8 (S4) ◽  
Author(s):  
Naiane Ferraz Bandeira Alves ◽  
Naiane Alves ◽  
Suênia Porpino ◽  
Matheus Monteiro ◽  
Thyago Queiroz ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Blood Pressure ◽  
Spontaneously Hypertensive Rats ◽  
Coconut Oil ◽  
Hypertensive Rats ◽  
Spontaneously Hypertensive ◽  
And Oxidative Stress

Tubuloglomerular feedback and autoregulation in spontaneously hypertensive rats

1990 ◽  
Vol 258 (6) ◽  
pp. F1479-F1489 ◽  
Author(s):  
F. H. Daniels ◽  
W. J. Arendshorst ◽  
R. G. Roberds
Keyword(s):  
Blood Pressure ◽  
Arterial Blood Pressure ◽  
Ureteral Obstruction ◽  
Spontaneously Hypertensive Rats ◽  
Control Period ◽  
Tubuloglomerular Feedback ◽  
Hypertensive Rats ◽  
Two Phase ◽  
Spontaneously Hypertensive ◽  
Arterial Blood

Experiments were conducted in 8-wk-old spontaneously hypertensive rats to determine whether tubuloglomerular feedback is essential for the autoregulation of renal blood flow. Autoregulation curves were obtained by measuring mean renal arterial blood pressure and flow during graded aortic occlusion. Renal vascular admittance was calculated from recordings of pulsatile renal arterial blood pressure and flow during induced atrial fibrillation. After a control period, acute ureteral obstruction was used to suppress tubuloglomerular feedback, as confirmed by measuring stop-flow pressure responses to rapid perfusion of Henle's loop. Ureteral obstruction did not impair steady-state autoregulation. During both the control and obstruction periods, the admittance gain was less than 1 at frequencies below 0.2 Hz, indicating dynamic autoregulatory activity. The control admittance contained two gain shoulders and two phase maxima, suggesting the presence of two control systems with response half-times of 1 and 10 s. During ureteral obstruction, the low-frequency shoulder and maximum disappeared, indicating that the slower system was no longer active. However, the high-frequency shoulder and maximum persisted, suggesting continued activity of the faster system. Collectively, these observations indicate the existence of a rapidly acting intrarenal control mechanism, in young spontaneously hypertensive rats, that may provide efficient autoregulation without assistance from tubuloglomerular feedback.

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.

The Relationship Between Angiotensin II (ANG II) and Oxidative Stress in the Maintenance of Mean Arterial Pressure (MAP) of Spontaneously Hypertensive Rats.

Hypertension ◽  
2000 ◽  
Vol 36 (suppl_1) ◽  
pp. 686-686
Author(s):  
Rodney J Bolterman ◽  
Clara M Ortiz-Ruiz ◽  
Luis A Juncos ◽  
Jane F Reckelhoff ◽  
Juan C Romero
Keyword(s):  
Oxidative Stress ◽  
Blood Pressure ◽  
Plasma Levels ◽  
Spontaneously Hypertensive Rats ◽  
Enzyme Inhibitor ◽  
Ang Ii ◽  
Converting Enzyme ◽  
Hypertensive Rats ◽  
Spontaneously Hypertensive ◽  
Converting Enzyme Inhibitor

48 Spontaneously hypertensive rats (SHR) reportedly have inappropriately high levels of Ang II despite normal plasma renin activity (PRA). Because Ang II stimulates oxidative stress, which in turn quenches nitric oxide, it is possible that Ang II-induced increases in oxidative stress contribute to the increase in blood pressure. Indeed, administering either a converting enzyme inhibitor (to decrease Ang II) or Tempol (a potent antioxidant) reduces blood pressure in SHR. We tested whether decreasing Ang II with a converting enzyme inhibitor reduces oxidative stress as well as MAP in SHR. For this, we divided 12 weeks old SHR into two groups (n=5 each). One group was treated with captopril (100 mg/kg/day added to the drinking water) and the other served as our untreated time controls. After 16 days of treatment, the rats were anesthetised and we measured MAP and collected blood samples to determine PRA, and the plasma levels of Ang II and thiobarbituric acid-reactive substances (TBARS). The captopril-treated rats had a lower MAP than the untreated rats (92±4 vs. 160±5 mmHg, respectively) and an increased PRA (42±1 vs. 26±6 ng/ml/h; captopril-treated vs. untreated rats, respectively). The decreased MAP in the captopril-treated SHR was accompanied by reduced plasma levels of Ang II (630±47 vs. 836±205 pg/ml) and TBARS (5.4±1.0 vs. 3.0±0.2 nmol/ml). Despite the significant decrease in Ang II levels in the captopril-treated SHR, they are still 20-fold higher rhan in normotensive Sprague-Dawley rats (34.0±8.8 pg/ml). In summary, captopril-induced decreases of MAP in SHR are accompanied not only by reduced levels of Ang II, but also by reduced oxidative stress. Because antioxidants also lower MAP in SHR, it suggests that oxidative stress induced by Ang II may play a role in the pathogenesis of the increased blood pressure in SHR.

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