Potentiation of the Hypotensive Effect of Bradykinin by Short-term Infusion of Angiotensin-(1-7) in Normotensive and Hypertensive Rats

Lima, Celso V.; Paula, Renata Dutra de; Resende, Fernanda L.; Khosla, M. C.; Santos, Robson Augusto Souza

doi:10.1161/01.hyp.30.3.542

Cited by 76 publications

(61 citation statements)

References 30 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…This BK-potentiating effect of Ang-(1-7) may contribute for its cardiovascular effects in normotensive (Paula et al 1995, Oliveira et al 1999, Greco et al 2006 and hypertensive (Lima et al 1997, Fernandes et al 2001 rats. Several mechanisms have been proposed to explain the BK-potentiating activity of Ang-(1-7), including ACE inhibition since Ang-(1-7) is an ACE substrate (Li et al 1997, Tom et al 2001, allosteric changes in ACE (Erdos et al 2002), and Mas-mediated changes in the BK signaling (Paula et al 1995, Oliveira et al 1999, Fernandes et al 2001, Ferreira et al 2001.…”

Section: Vascular Actions Of the Ace2/ang-(1-7)/mas Axismentioning

confidence: 93%

Angiotensin-converting enzyme 2, angiotensin-(1–7) and Mas: new players of the renin–angiotensin system

Santos

Ferreira

Verano‐Braga

et al. 2012

Journal of Endocrinology

432

369

View full text Add to dashboard Cite

Angiotensin (Ang)-(1-7) is now recognized as a biologically active component of the reninangiotensin system (RAS). Ang-(1-7) appears to play a central role in the RAS because it exerts a vast array of actions, many of them opposite to those attributed to the main effector peptide of the RAS, Ang II. The discovery of the Ang-converting enzyme (ACE) homolog ACE2 brought to light an important metabolic pathway responsible for Ang-(1-7) synthesis. This enzyme can form Ang-(1-7) from Ang II or less efficiently through hydrolysis of Ang I to Ang-(1-9) with subsequent Ang-(1-7) formation by ACE. In addition, it is now well established that the G protein-coupled receptor Mas is a functional binding site for Ang-(1-7). Thus, the axis formed by ACE2/Ang-(1-7)/Mas appears to represent an endogenous counterregulatory pathway within the RAS, the actions of which are in opposition to the vasoconstrictor/ proliferative arm of the RAS consisting of ACE, Ang II, and AT 1 receptor. In this brief review, we will discuss recent findings related to the biological role of the ACE2/Ang-(1-7)/Mas arm in the cardiovascular and renal systems, as well as in metabolism. In addition, we will highlight the potential interactions of Ang-(1-7) and Mas with AT 1 and AT 2 receptors.

show abstract

Section: Vascular Actions Of the Ace2/ang-(1-7)/mas Axismentioning

confidence: 93%

Angiotensin-converting enzyme 2, angiotensin-(1–7) and Mas: new players of the renin–angiotensin system

Santos

Ferreira

Verano‐Braga

et al. 2012

Journal of Endocrinology

432

369

View full text Add to dashboard Cite

show abstract

“…Several reports have described a BKpotentiating activity for Ang-(1-7) (10)(11)(12)(13)(14)(15) that could contribute to the cardiovascular effects of ACE inhibition and AT 1 receptor blockers (16). The Ang-(1-7)-BK interaction has been studied in vivo (10,11), in cell culture (12) or in isolated vessels (14).…”

Section: Introductionmentioning

confidence: 99%

“…The Ang-(1-7)-BK interaction has been studied in vivo (10,11), in cell culture (12) or in isolated vessels (14). However, there are no data available about the interaction between Ang-(1-7) and BK in the heart.…”

Section: Introductionmentioning

confidence: 99%

Angiotensin-(1-7) potentiates the coronary vasodilatatory effect of bradykinin in the isolated rat heart

Almeida

Frábregas

Madureira

et al. 2000

Braz J Med Biol Res

View full text Add to dashboard Cite

It has been shown that angiotensin-(1-7) (Ang-(1-7)) infusion potentiates the bradykinin (BK)-induced hypotensive response in conscious rats. The present study was conducted to identify Ang-(1-7)-BK interactions in the isolated rat heart perfused according to the Langendorff technique. Hearts were excised and perfused through the aortic stump under a constant flow with Krebs-Ringer solution and the changes in perfusion pressure and heart contractile force were recorded. Bolus injections of BK (2.5, 5, 10 and 20 ng) produced a dosedependent hypotensive effect. Ang-(1-7) added to the perfusion solution (2 ng/ml) did not change the perfusion pressure or the contractile force but doubled the hypotensive effect of the lower doses of BK. The BK-potentiating Ang-(1-7) activity was blocked by pretreatment with indomethacin (5 mg/kg, ip) or L-NAME (30 mg/kg, ip). The Ang-(1-7) antagonist A-779 (50 ng/ml in Krebs-Ringer) completely blocked the effect of Ang-(1-7) on BK-induced vasodilation. These data suggest that the potentiation of the BK-induced vasodilation by Ang-(1-7) can be attributed to the release of nitric oxide and vasodilator prostaglandins through an Ang-(1-7) receptor-mediated mechanism.

show abstract

“…The receptor Mas is blocked by the heptapeptide D-Ala(7)-Ang(1-7) [A-779], a specific and potent antagonist of Ang(1-7), 9 disrupting hemodynamic and renal responses to Ang(1-7), such as the antidiuretic effect 10 and bradykinin potentiation in vivo and in mesenteric microvessels. 11,12 Recently Wiemer et al 13 described a novel nonpeptide compound, AVE 0991 (AVE), which was able to evoke effects on endothelial cells similar to those observed for Ang(1-7). AVE and Ang(1-7) stimulated nitric oxide (NO) release from cultured cells caused by the activation of endothelial NO synthase, and this effect was inhibited by the NO synthase inhibitor L-NMMA.…”

mentioning

confidence: 98%

Short-Term Angiotensin(1-7) Receptor Mas Stimulation Improves Endothelial Function in Normotensive Rats

2005

View full text Add to dashboard Cite

Abstract-In this study we evaluated the effect of angiotensin(1-7) and its nonpeptide analog, AVE 0991, on the endothelial function in vivo. The experiments were performed in conscious adult male Wistar rats, with polyethylene catheters implanted into the descending aorta (through left carotid artery), for injection of acetylcholine or sodium nitroprusside, femoral artery for mean arterial pressure and heart rate measurement; and femoral vein for drug administration. Increasing doses of acetylcholine (3.1 ng to 25.0 ng) or nitroprusside (1.0 g to 10.0 g) were administered before and 30 minutes after the start of the infusion of: angiotensin(1-7) (0.7 and 7.0 pmol/min); A-779 (180 pmol/min); angiotensin(1-7) (7.0 pmol/min) combined with A-779 (180 pmol/min); AVE 0991 (11, 45, and 230 pmol/min); AVE 0991 (45 pmol/min) combined with A-779 (180 pmol/min), or vehicle (6 L/min). Baseline mean arterial pressure and heart rate were not altered during angiotensin(1-7) or AVE 0991 infusion. Angiotensin(1-7) (0.7 pmol/min) infusion produced a significant potentiation of the hypotensive effect of acetylcholine (3.1 ng: Ϫ9Ϯ1 mm Hg before; Ϫ18Ϯ2 mm Hg after; PϽ0.05). A similar potentiation was observed with the higher dose of angiotensin(1-7).As observed for angiotensin(1-7), infusion of AVE 0991 at 230 pmol/min potentiated the acetylcholine effect (3. Key Words: angiotensin Ⅲ endothelium Ⅲ nitric oxide Ⅲ renin-angiotensin system T he renin-angiotensin system (RAS) plays an important role in cardiovascular physiology and cell function. 1 The renin-angiotensin system is usually known as a hormonal and tissular system that releases angiotensin II (Ang II) and is involved in the regulation of blood pressure and salt and fluid homeostasis. It is becoming evident that the renin-angiotensin system has 2 major arms: a vasoconstrictor/proliferative in which the main mediator is Ang II, and a vasodilator/anti-proliferative, in which the major effector is angiotensin(1-7) [Ang(1-7)] acting on the G proteincoupled receptor Mas. 2 Angiotensin(1-7) is a biologically active heptapeptide, which can be formed in a pathway independent of the angiotensin-converting enzyme. The blood vessels are an important site for the formation and biological actions of Ang(1-7). 3 In contrast to Ang II, Ang(1-7) is neither dipsogen nor an aldosterone secretagogue, but similarly to Ang II, it releases vasopressin, prostaglandins, and nitric oxide. 3 Ang(1-7) can improve the baroreceptor reflex 4,5 and decrease smooth muscle cell growth. 6 Peripherally, the most important actions of Ang(1-7) appear to be related to the control of hydroelectrolyte balance 7 and cardiovascular function. 8 We have recently shown that Ang(1-7) is an endogenous ligand for the G protein-coupled receptor Mas. 2 Because Ang(1-7) seems to counteract many of Ang II cardiovascular effects, this peptide and its receptor are potential targets for the development of cardioprotective or anti-hypertensive agents. The receptor Mas is blocked by the heptapeptide D-Ala(7)-Ang(1-7) [A-779], a sp...

show abstract

Potentiation of the Hypotensive Effect of Bradykinin by Short-term Infusion of Angiotensin-(1-7) in Normotensive and Hypertensive Rats

Cited by 76 publications

References 30 publications

Angiotensin-converting enzyme 2, angiotensin-(1–7) and Mas: new players of the renin–angiotensin system

Angiotensin-converting enzyme 2, angiotensin-(1–7) and Mas: new players of the renin–angiotensin system

Angiotensin-(1-7) potentiates the coronary vasodilatatory effect of bradykinin in the isolated rat heart

Short-Term Angiotensin(1-7) Receptor Mas Stimulation Improves Endothelial Function in Normotensive Rats

Contact Info

Product

Resources

About