scholarly journals Chronic NF-κB blockade improves renal angiotensin II type 1 receptor functions and reduces blood pressure in Zucker diabetic rats

2015 ◽  
Vol 14 (1) ◽  
Author(s):  
Hao Luo ◽  
Xinquan Wang ◽  
Jialiang Wang ◽  
Caiyu Chen ◽  
Na Wang ◽  
...  
Keyword(s):  
Blood Pressure ◽  
Angiotensin Ii ◽  
Diabetic Rats

scholarly journals Mitochondrial angiotensin II receptors regulate oxygen consumption in kidney mitochondria from healthy and type 1 diabetic rats

2020 ◽  
Vol 318 (3) ◽  
pp. F683-F688 ◽  
Author(s):  
Malou Friederich-Persson ◽  
Patrik Persson
Keyword(s):  
Nitric Oxide ◽  
Oxygen Consumption ◽  
Angiotensin Ii ◽  
Receptor Antagonist ◽  
Diabetic Rats ◽  
Kidney Cortex ◽  
Ang Ii ◽  
Kidney Mitochondria ◽  
Receptor Inhibition

Exaggerated activation of the renin-angiotensin-aldosterone system (RAAS) is a key feature in diseases such as hypertension, diabetes, and chronic kidney disease. Recently, an intracellular RAAS was demonstrated with angiotensin II (ANG II) type 1 (AT1) and type 2 (AT2) receptors expressed in nuclei and mitochondria. Diabetes is associated with both mitochondrial dysfunction and increased intracellular ANG II concentration in the kidney cortex. The present study investigated the role of ANG II signaling in kidney cortex mitochondria isolated from control and streptozotocin-induced diabetic rats. Mitochondrial oxygen consumption was evaluated after addition of ANG II alone or after preincubation with candesartan (AT1 receptor antagonist), PD-123319 (AT2 receptor antagonist), or the two in combination. ANG II binds to only mitochondrial AT2 receptors in control rats and both AT1 receptors and AT2 receptors in diabetic rats. ANG II decreased oxygen consumption in mitochondria from both control and diabetic rats. ANG II response was reversed to increased oxygen consumption by the nitric oxide synthase inhibitor N-nitro-l-arginine methyl ester. AT1 receptor inhibition did not affect the response to ANG II, whereas AT2 receptor inhibition abolished the response in mitochondria from control rats and reversed the response to increased oxygen consumption through superoxide-induced mitochondrial uncoupling in mitochondria from diabetic rats. ANG II decrease mitochondrial respiration via AT2 receptor-mediated nitric oxide release in both control and diabetic rats. AT1 receptors do not regulate mitochondria function in control rats, whereas ANG II via AT1 receptors increase mitochondria leak respiration in diabetic animals.

scholarly journals Addition of a Nitric Oxide Donor to an Angiotensin II Type 1 Receptor Blocker May Cancel Its Blood Pressure-Lowering Effects

2015 ◽  
Vol 56 (6) ◽  
pp. 656-660 ◽  
Author(s):  
Eiji Yahiro ◽  
Shin-ichiro Miura ◽  
Yasunori Suematsu ◽  
Yoshino Matsuo ◽  
Tadaaki Arimura ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Blood Pressure ◽  
Angiotensin Ii ◽  
Receptor Blocker ◽  
Nitric Oxide Donor ◽  
Blood Pressure Lowering ◽  
Pressure Lowering

scholarly journals Effects of YM358, an Angiotensin II Type 1(AT1) Receptor Antagonist, and Enalapril on Blood Pressure and Vasoconstriction in Two Renal Hypertension Models.

2000 ◽  
Vol 23 (2) ◽  
pp. 174-181 ◽  
Author(s):  
Tomoko TOKIOKA ◽  
Masayuki SHIBASAKI ◽  
Akira FUJIMORI ◽  
Yasuko MATSUDA-SATOH ◽  
Wataru UCHIDA ◽  
...  
Keyword(s):  
Blood Pressure ◽  
Angiotensin Ii ◽  
Receptor Antagonist ◽  
Renal Hypertension ◽  
At1 Receptor

ANG II enhances contractile responses via PI3-kinase p110δ pathway in aortas from diabetic rats with systemic hyperinsulinemia

2006 ◽  
Vol 291 (2) ◽  
pp. H846-H853 ◽  
Author(s):  
Tsuneo Kobayashi ◽  
Yuko Hayashi ◽  
Kumiko Taguchi ◽  
Takayuki Matsumoto ◽  
Katsuo Kamata
Keyword(s):  
Blood Pressure ◽  
Enzyme Inhibitor ◽  
Chronic Administration ◽  
Diabetic Rats ◽  
Ang Ii ◽  
Phosphatidylinositol 3 Kinase ◽  
Contractile Responses ◽  
Vascular Contractility ◽  
K Activity

We investigated the involvement of ANG II and phosphatidylinositol 3-kinase (PI3-K) in the enhanced aortic contractile responses induced by hyperinsulinemia in chronic insulin-treated Type 1 diabetic rats. Plasma ANG II levels were elevated in untreated compared with control diabetic rats and further increased in insulin-treated diabetic rats. Aortic contractile responses and systolic blood pressure were significantly enhanced in chronic insulin-treated diabetic rats compared with the other groups. These insulin-induced increases were largely prevented by cotreatment with losartan (an ANG II type 1 receptor antagonist) or enalapril (an angiotensin-converting enzyme inhibitor). LY-294002 (a PI3-K inhibitor) diminished the increases in contractile responses in ANG II-incubated aortas and aortas from chronic insulin-treated diabetic rats. The norepinephrine (NE)-stimulated levels of p110δ-associated PI3-K activity and p110δ protein expression were increased in aortas from insulin-treated diabetic compared with control and untreated diabetic rats, and chronic administration of losartan blunted these increases. Contractions were significantly larger in aortas from diabetic rats incubated with a low concentration (inducing ∼10% of the maximum contraction) of ANG II or with NE or isotonic K+ than in aortas from nonincubated diabetic rats. NE-stimulated p110 PI3-K activity was elevated in aortas from diabetic rats coincubated with a noncontractile dose of ANG II. These results suggest that, in insulin-treated Type 1 diabetic rats with hyperinsulinemia, chronic ANG II type 1 receptor blockade blunts the increases in vascular contractility and blood pressure via a decrease in p110δ-associated PI3-K activity.

scholarly journals Angiotensin II type 1 receptor A1166C polymorphism in relation to incident cardiovascular events, hypertension, and blood pressure control in elderly Caucasians and African Americans

Circulation ◽  
2001 ◽  
Vol 103 (suppl_1) ◽  
pp. 1354-1354
Author(s):  
Lucia A. Hindorff ◽  
Susan R. Heckbert ◽  
Russ Tracy ◽  
Zhonghua Tang ◽  
Bruce M. Psaty ◽  
...  
Keyword(s):  
Blood Pressure ◽  
Angiotensin Ii ◽  
African Americans ◽  
Ace Inhibitors ◽  
Cardiovascular Events ◽  
Large Population ◽  
Antihypertensive Agents ◽  
Cardiovascular Health Study ◽  
A1166c Polymorphism

P17 Objective: The C allele of the angiotensin II type 1 receptor (AT1R) A1166C polymorphism has been associated in several studies with increased risks of hypertension (HTN) and myocardial infarction (MI), and with enhanced blood pressure (BP) response to ACE inhibitors but not calcium antagonists. Most of these studies were small, and none included large numbers of African Americans. We examined these associations in the Cardiovascular Health Study, an observational cohort study of risk factors for coronary disease and stroke in men and women ≥ 65 years of age. Methods: All 771 self-identified African Americans plus 1333 randomly-selected Caucasians were genotyped for the AT1R polymorphism. BP, medication use, and HTN were assessed annually. Incident MI/coronary death (CHD, n = 125 in whites; n = 60 in blacks), incident total cardiovascular events (CVD, n = 226 in whites; n = 101 in blacks), incident congestive heart failure (CHF, n = 146 in whites; n = 55 in blacks), and incident HTN (n = 184 in whites; n = 85 in blacks) were identified during up to 8 years of follow-up. Results: Genotype frequency distributions differed between whites (AA 49%, AC 41%, CC 10%) and blacks (85%, 15%, 1%, p < 0.0005). Age, gender or HTN at baseline did not differ by genotype in either group. In both whites and blacks, genotype was not associated with incident CHD (HR for AC/CC vs. AA, 95% CI in whites = 1.0, 0.7-1.5; blacks, HR = 0.7, 0.3-1.5), incident total CVD events (whites, HR = 1.0, 0.8-1.3; blacks, HR = 0.9, 0.5-1.6), incident CHF (whites, HR = 1.1, 0.8-1.5; blacks, 0.6, 0.3-1.4) or newly-identified HTN (whites, HR = 0.8, 0.6-1.1; blacks, HR = 1.1, 0.6-1.9). Among treated hypertensives, the association of genotype with controlled BP (<140/<90) did not differ between users of calcium channel blockers and users of ACE inhibitors in either race. Conclusion: In this large population-based elderly cohort, the AT1R A1166C polymorphism was not associated with prevalent or newly-identified HTN, incident CVD events, or BP response to antihypertensive agents in either Caucasians or African Americans.

scholarly journals Effects of Prehypertensive Losartan Treatment on Resistance Vessel Remodeling and Angiotensin II Type 1 Receptor Expression in Spontaneously Hypertensive Rats

2020 ◽  
Vol 33 (5) ◽  
pp. 471-471
Author(s):  
Ting-jun Wang ◽  
Wan-ru Chen ◽  
Xu Lin ◽  
Gui-li Lian ◽  
Chang-sheng Xu ◽  
...  
Keyword(s):  
Blood Pressure ◽  
Angiotensin Ii ◽  
Receptor Expression ◽  
Mesenteric Arteries ◽  
Resistance Vessel ◽  
Spontaneously Hypertensive ◽  
Vessel Remodeling ◽  
Wistar Kyoto ◽  
Losartan Treatment

Abstract Background To study the effects of prehypertensive losartan treatment on blood pressure, resistance vessel remodeling, and angiotensin II type 1 receptor (AT1R) expression in adult spontaneously hypertensive rats (SHRs). Methods Four-week-old SHR and Wistar-Kyoto rats were randomly divided into losartan-treated and untreated groups. Losartan was administrated by gavage from 4 to 10 weeks old. Blood pressure was monitored by the tail-cuff method till 26 weeks old. The third grade mesenteric arteries were then isolated. Vessel structure, relaxation reactivity, angiotensin II type 1 receptor expression, and angiotensin II levels were analyzed. Results Losartan treatment from 4 to 10 weeks of age significantly lowered systolic blood pressure from 10 to 26 weeks in SHR. At 26 weeks old, wall thickness to lumen radius and wall area to lumen area of mesenteric arteries were significantly lower in losartan-treated than untreated SHR (P &lt; 0.01). Maximum relaxation to acetylcholine and its pD2 were increased in losartan-treated compared to untreated SHR (P &lt; 0.01). Angiotensin II type 1 receptor mRNA and protein levels were significantly reduced in losartan-treated SHR (P &lt; 0.01). However, angiotensin II levels in plasma and mesenteric arteries of losartan-treated SHR were higher than those of untreated SHR (P &lt; 0.05). Losartan treatment lowered systolic blood pressure in Wistar-Kyoto at the age of 10 weeks (P &lt; 0.05), but had no significant effect on blood pressure after 14 weeks or mesenteric arteries at 26 weeks. Conclusions Blood pressure reduction induced by prehypertensive losartan treatment ameliorates resistance vessel remodeling and downregulates angiotensin II type 1 receptor expression in adult SHR.

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