Interactions Between Angiotensin-(1-7), Kinins, and Angiotensin II in Kidney and Blood Vessels

Abstract

Abstract-The heptapeptide angiotensin (Ang)-(1-7) is currently considered one of the biologically active end products of the renin-angiotensin system. The formation of Ang-(1-7) by pathways independent of Ang II generation, the selectivity of its actions, and its peculiar property of exhibiting effects that are partially opposite of those of the parent compound, Ang II, confer a unique biochemical and functional profile to this peptide. In this article, we will review novel aspects of the biological actions of Ang-(1-7), dealing with its interaction with Ang II and kinins, especially in the kidney and blood vessels. Key Words: bradykinin Ⅲ renin-angiotensin system Ⅲ receptors, angiotensin T he heptapeptide angiotensin (Ang)-(1-7) is formed from Ang I and Ang II by tissue peptidases, including neutral endopeptidase (neprilysin), thimet oligopeptidase, prolylcarboxypeptidase, and prolyl-endopeptidase. 1 In addition, the possibility should be considered that at least in the kidney and heart, Ang-(1-7) could be formed from Ang I or Ang II by a pathway involving the ACE-related enzyme ACE2 2,3 ( Figure 1). Once formed, Ang-(1-7) is rapidly hydrolyzed, especially by ACE. 4 Therefore, in the presence of ACE inhibition, the levels of Ang-(1-7), which circulates in blood at concentrations close to those of Ang II, raises several-fold, 5 probably owing to both the increase in Ang I concentration and the decrease in Ang-(1-7) breakdown. The related observation that Ang-(1-7) can increase following long-term administration of angiotensin type 1 (AT 1 ) receptor blockers 1 raises the possibility that Ang-(1-7) contributes to the pharmacological effects of both ACE inhibitors and AT 1 receptor antagonists. Interactions between Ang-(1-7) and Kinins in Blood VesselsMost of the interactions between Ang-(1-7) and bradykinin (BK) have been reported to occur in blood vessels. 1,6 -11 There are 2 major types of interaction: potentiation of BK by Ang-(1-7) and mediation of the vascular actions of Ang-(1-7) by kinins, although the latter does not exclude the former. Potentiation of BK by Ang-(1-7) has been observed in conscious normotensive and hypertensive rats in terms of the BK hypotensive effect in the whole animal 1,6 or the vasodilating action of BK in rat mesenteric microvessels in situ. 1,7 Brosnihan and colleagues 8,9 have shown that preincubation of isolated dog coronary arteries with Ang-(1-7) increased the relaxation produced by BK. Similarly, Almeida et al 10 have shown that Ang-(1-7) at 2 nmol/L concentration increased the vasodilation produced by BK in isolated rat hearts. Interestingly, the venoconstriction produced by BK in rabbit endothelium denuded femoral vein was also potentiated by Ang-(1-7), 11 indicating that the BK potentiating activity of Ang- (1-7) is not an exclusively endothelium-dependent phenomenon. Potentiation of bradykinin by Ang-(1-7) has also been described in other preparations. In Chinese hamster ovary cells co-transfected with the human cDNA for BK-B 2 receptors and ACE, Deddish et al 12 descri...

Development of hepatorenal syndrome in bile duct ligated rats

“…During hepatic damage, systemic vasodilation and hyperdynamic circulation have been observed [16] , which in turn promote an increase in sympathetic nervous activity, plasma renin activity (PRA), angiotensin Ⅱ and aldosterone levels, especially in the presence of HRS [3,4] . It is well known that angiotensin Ⅱ is one of the most powerful regulators of sodium excretion, operating through extrarenal as well as intrarenal mechanisms [17][18][19] . Some authors believe that, at the early stages of hepatic injury, the renal effects of angiotenisin Ⅱ represent a compensatory mechanism against the drop in organ perfusion pressure [3,4] .…”

“…However, we still do not know how angiotensin-(1-7) could affect renal function in BDL rats. It has been clearly demonstrated that angiotensin-(1-7) also exerts complex renal actions [19,21,22] . Our group and others detected in vivo and in vitro antidiuretic effects of angiotensin-(1-7) by increasing fluid reabsorption [23][24][25][26] .…”

The Role of Angiotensin II Receptor 1 (AT1) Blockade in Cisplatin-Induced Nephrotoxicity in Rats: Gender-Related Differences

“…The inhibition of AT1 with losartan may cause AT2 and Mas vasodilatation responses in females more than in males. 28,29 Therefore, a greater blood flow may transport more CP into the kidney, and causes more tissue damage.…”

Disparate Roles of AT 2 Receptors in the Renal Cortical and Medullary Circulations of Anesthetized Rabbits

“…We tested the responses to angiotensin II itself, angiotensin III (moderate selectivity for AT 2 receptors 20,21 ), the highly selective AT 2 agonist CGP42112A, 22 and angiotensin(1-7), because the latter has both a high affinity for AT 2 receptors 21 and vasodilator effects that are possibly mediated independently of AT 1 and AT 2 receptors. 23 …”