Effects of Angiotensin II Type 1 Receptor Antagonist on Nitric Oxide Synthase Expression and Myocardial Remodeling in Goldblatt Hypertensive Rats

2000 ◽  
Vol 35 (4) ◽  
pp. 564-571 ◽  
Author(s):  
Teruo Higashi ◽  
Naohiko Kobayashi ◽  
Kazuyoshi Hara ◽  
Hiromichi Shirataki ◽  
Hiroaki Matsuoka
Keyword(s):  
Nitric Oxide ◽  
Angiotensin Ii ◽  
Nitric Oxide Synthase ◽  
Receptor Antagonist ◽  
Myocardial Remodeling ◽  
Hypertensive Rats ◽  
Oxide Synthase

Angiotensin II type 1 receptor blocker preserves tolerance to ischemia-reperfusion injury in Dahl salt-sensitive rat heart

2008 ◽  
Vol 294 (6) ◽  
pp. H2473-H2479 ◽  
Author(s):  
Seiji Matsuhisa ◽  
Hajime Otani ◽  
Toru Okazaki ◽  
Koji Yamashita ◽  
Yuzo Akita ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Nitric Oxide ◽  
Angiotensin Ii ◽  
Nitric Oxide Synthase ◽  
Infarct Size ◽  
Rat Heart ◽  
Ischemia Reperfusion Injury ◽  
Ischemia Reperfusion ◽  
Oxide Synthase

Oxidative stress is involved in the tolerance to ischemia-reperfusion (I/R) injury. Because angiotensin II type 1 receptor blockers (ARBs) inhibit oxidative stress, there is concern that ARBs abolish the tolerance to I/R injury. Dahl salt-sensitive (DS) hypertensive and salt-resistant (DR) normotensive rats received an antioxidant, 2-mercaptopropionylglycine (MPG), or an ARB, losartan, for 7 days. Losartan and MPG significantly inhibited oxidative stress as determined by tissue malondialdehyde + 4-hydroxynoneal and increased expression of inducible nitric oxide synthase (iNOS) in the DS rat heart. However, losartan but not MPG activated endothelial nitric oxide synthase (eNOS) as assessed by phosphorylation of eNOS on Ser1177. Infarct size after 30-min left coronary artery occlusion followed by 2-h reperfusion was comparable between DS and DR rat hearts. Although MPG and losartan had no effect on infarct size in the DR rat heart, MPG but not losartan significantly increased infarct size in the DS rat heart. A selective iNOS inhibitor, 1400W, increased infarct size in the DS rat heart, but it had no effect on infarct size in the losartan-treated DS rat heart. However, a nonselective NOS inhibitor, Nω-nitro-l-arginine methyl ester, increased infarct size in the losartan-treated DS rat heart. These results suggest that losartan preserves the tolerance to I/R injury by activating eNOS despite elimination of redox-sensitive upregulation of iNOS and iNOS-dependent cardioprotection in the DS rat heart.

Angiotensin II decreases inducible nitric oxide synthase expression in rat astroglial cultures

1995 ◽  
Vol 268 (3) ◽  
pp. C700-C707 ◽  
Author(s):  
L. J. Chandler ◽  
K. Kopnisky ◽  
E. Richards ◽  
F. T. Crews ◽  
C. Sumners
Keyword(s):  
Nitric Oxide ◽  
Angiotensin Ii ◽  
Nitric Oxide Synthase ◽  
Receptor Antagonist ◽  
Maximal Response ◽  
No Production ◽  
Dependent Manner ◽  
Ang Ii ◽  
Subsequent Formation ◽  
Oxide Synthase

Consistent with stimulation of expression of an inducible form of nitric oxide synthase (iNOS), exposure of rat astroglial cultures to lipopolysaccharide (LPS) caused a time-dependent increase in the accumulation of nitrite in the culture media. Addition of the peptide angiotensin II (ANG II) with LPS decreased subsequent formation of nitrite in a concentration-dependent manner (concentration inhibiting 50% of maximal response approximately 1 nM). The ANG II effect could be blocked by the ANG II type 1 (AT1 receptor antagonist losartan but not by the ANG II type 2 (AT2) receptor antagonist PD-123177. ANG II had no effect on nitrite formation stimulated by a combination of inflammatory cytokines (interleukin-1 beta, tumor necrosis factor-alpha, and interferon-gamma). A brief 10-min exposure to ANG II was sufficient to cause an approximately 30% inhibition of the LPS response, with maximal inhibition of approximately 65% after 3 h, and occurred only when ANG II was added during the iNOS induction phase. Consistent with partial inhibition of LPS-stimulated expression of iNOS, ANG II reduced the levels of both iNOS mRNA and iNOS protein. These results demonstrate that ANG II can decrease LPS-stimulated NO production in astroglia by inhibiting induction of iNOS expression.

Angiotensin II stimulates nitric oxide production in pulmonary artery endothelium via the type 2 receptor

2004 ◽  
Vol 287 (3) ◽  
pp. L559-L568 ◽  
Author(s):  
Susan Olson ◽  
Richard Oeckler ◽  
Xinmei Li ◽  
Litong Du ◽  
Frank Traganos ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Endothelial Cells ◽  
Angiotensin Ii ◽  
Nitric Oxide Synthase ◽  
Pulmonary Artery ◽  
Nitric Oxide Production ◽  
Oxide Production ◽  
Oxide Synthase

We previously reported that angiotensin II stimulates an increase in nitric oxide production in pulmonary artery endothelial cells. The aims of this study were to determine which receptor subtype mediates the angiotensin II-dependent increase in nitric oxide production and to investigate the roles of the angiotensin type 1 and type 2 receptors in modulating angiotensin II-dependent vasoconstriction in pulmonary arteries. Pulmonary artery endothelial cells express both angiotensin II type 1 and type 2 receptors as assessed by RT-PCR, Western blot analysis, and flow cytometry. Treatment of the endothelial cells with PD-123319, a type 2 receptor antagonist, prevented the angiotensin II-dependent increase in nitric oxide synthase mRNA, protein levels, and nitric oxide production. In contrast, the type 1 receptor antagonist losartan enhanced nitric oxide synthase mRNA levels, protein expression, and nitric oxide production. Pretreatment of the endothelial cells with either PD-123319 or an anti-angiotensin II antibody prevented this losartan enhancement of nitric oxide production. Angiotensin II-dependent enhanced hypoxic contractions in pulmonary arteries were blocked by the type 1 receptor antagonist candesartan; however, PD-123319 enhanced hypoxic contractions in angiotensin II-treated endothelium-intact vessels. These data demonstrate that angiotensin II stimulates an increase in nitric oxide synthase mRNA, protein expression, and nitric oxide production via the type 2 receptor, whereas signaling via the type 1 receptor negatively regulates nitric oxide production in the pulmonary endothelium. This endothelial, type 2 receptor-dependent increase in nitric oxide may serve to counterbalance the angiotensin II-dependent vasoconstriction in smooth muscle cells, ultimately regulating pulmonary vascular tone.

Angiotensin-(1–7) upregulates cardiac nitric oxide synthase in spontaneously hypertensive rats

2010 ◽  
Vol 299 (4) ◽  
pp. H1205-H1211 ◽  
Author(s):  
María A. Costa ◽  
María A. Lopez Verrilli ◽  
Karina A. Gomez ◽  
Pablo Nakagawa ◽  
Clara Peña ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Nitric Oxide Synthase ◽  
Receptor Antagonist ◽  
Spontaneously Hypertensive Rats ◽  
Ventricular Myocytes ◽  
Hypertensive Rats ◽  
Spontaneously Hypertensive ◽  
Enos Phosphorylation ◽  
Oxide Synthase

It has been shown that angiotensin (ANG)-(1–7) activates nitric oxide synthase (NOS) in isolated ventricular myocytes from normotensive rats. Since many ANG-(1–7) actions are enhanced in situations of increased ANG II activity, as in hypertension, in this study we investigated the in vivo effect of ANG-(1–7) on NOS activity and expression of endothelial (eNOS), neuronal (nNOS), and inducible NOS (iNOS) in ventricles from spontaneously hypertensive rats (SHR). Rats were subjected to a 60-min ANG-(1–7) infusion (0.35 nmol/min); controls received saline. NOS activity was measured using the NADPH diaphorase histochemical method and by the conversion of l-[14C]arginine to citrulline, and NOS phosphorylation and expression were determined using Western blotting. In SHR, ANG-(1–7) infusion diminished mean arterial pressure from 180 ± 9 to 146 ± 9 mmHg ( P < 0.05), and this effect was prevented by nitro-l-arginine methyl ester (l-NAME), a NOS inhibitor. In addition, NOS activity and eNOS phosphorylation were increased by ANG-(1–7) infusion. Ventricular eNOS and nNOS expression were increased 67.4 ± 6.4 and 51 ± 10%, respectively, by ANG-(1–7), whereas iNOS was not changed. In another set of experiments, we evaluated the mechanism by which ANG-(1–7) modifies NOS activity. Isolated ventricle slices preincubated with ANG-(1–7) showed an increase in NOS activity and eNOS phosphorylation, which was blocked by an AT2 and a bradykinin B2 receptor antagonist, but not by the Mas receptor antagonist. Our results show that in rats in a hypertensive state, ANG-(1–7) infusion upregulates cardiac NOS expression and activity through an AT2- and bradykinin-dependent mechanism. In this way ANG-(1–7) may elicit its cardioprotective action and contribute to some of the counterregulatory AT2 receptor effects that oppose the AT1 receptor-mediated effects.

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