The subtype-2 (AT2) angiotensin receptor regulates renal cyclic guanosine 3', 5'-monophosphate and AT1 receptor-mediated prostaglandin E2 production in conscious rats.

Abstract

The renal effects of angiotensin II(AII) are attributed to AT 1 receptors. In contrast, the function of renal AT 2 receptors is unknown. Using a microdialysis technique, we monitored changes in renal interstitial fluid (RIF) prostaglandin E 2 (PGE 2 ) and cyclic guanosine 3 Ј , 5 Ј -monophosphate (cGMP) in response to dietary sodium (Na) depletion alone, or Na depletion or normal Na diet combined with the AT 1 receptor blocker, Losartan, the AT 2 receptor blocker, PD 123319 (PD), or angiotensin II, individually or combined in conscious rats. Na depletion significantly increased PGE 2 and cGMP. During Na depletion, Losartan decreased PGE 2 and did not change cGMP. In contrast, PD significantly increased PGE 2 and decreased cGMP. Combined administration of Losartan and PD decreased PGE 2 and cGMP.During normal Na diet, RIF PGE 2 and cGMP increased in response to angiotensin II. Neither Losartan nor PD, individually or combined, changed RIF PGE 2 or cGMP. Combined administration of angiotensin II and Losartan or PD produced a significant decrease in response of PGE 2 and cGMP to angiotensin II, respectively.

Arachidonic acid mediates angiotensin II effects on p21ras in renal proximal tubular cells via the tyrosine kinase-Shc-Grb2-Sos pathway

“…The distribution of renal AT 2 receptor subtypes has not been precisely determined with the exception of the apical receptor on proximal tubular epithelial cells and glomerular endothelial cells (1,19). Signaling linked to AT 2 receptor includes activation of MAPK phosphatase, NO, guanylate cyclase, and PLA 2 (1,20,21,22). The current studies broaden our understanding of AT 2 -mediated signaling and document modulation of p21ras in proximal tubular epithelium.…”

Role of bradykinins and nitric oxide in the AT2 receptor-mediated hypotension

“…The mechanism whereby brain AT 2 receptor mediates vasodepressor response to footshocks may be explained through the release of substances such as bradykinin or NO. 40 AT 2 receptor may exert its vasodepressor effect by stimulating local release of nitric oxide either directly or via kinins 13,41 which together with blockade of the AT 1 receptor may have an vasodepressor effect.…”

“…40 Indeed, it has been shown that vasorelaxation in several experimental preparations is blocked by inhibitors of methylene blue, a soluble guanylyl cyclase inhibitor, suggesting a role for nitric oxide-guanylyl cyclase system. 11,42 It could be that the angiotensin AT 2 receptor exerts its haemodynamics effects by stimulating local release of nitric oxide either directly or via kinins 13,14,41 which together with the blockade of the angiotensin AT 1 receptor may have an vasodilator effect. It has been reported that in cultured bovine aortic endothelial cells, angiotensin II induces a sixto seven-fold increase in the release of cGMP; this effect was abolished by a kinin antagonist and a nitric oxide synthesis inhibitor and markedly inhibited by an angiotensin AT 2 receptor antagonist, but only marginally inhibited by an angiotensin AT 1 receptor antagonist, 14 suggesting that angiotensinstimulated release of nitric oxide is predominantly due to stimulation of the angiotensin AT 2 receptor and may lead to an increase in the effect of kinins, stimulation of nitric oxide and increased cGMP formation.…”

“…11,12 Angiotensin II may act on angiotensin AT 2 receptor subtype, either directly or via the release of autacoids such as kinins and nitric oxide. 13,14 In this respect, it has been shown that in cultured endothelial cells, angiotensin II increases nitric oxidedependent cyclic guanosine monophosphate (cGMP) production through the stimulation of the angiotensin AT 2 receptor, which in turn leads to an enhanced release of bradykinin. 15 Some of the actions of angiotensin II are centrally mediated.…”

Current status of angiotensin receptor blockers for the treatment of cardiovascular diseases: focus on telmisartan

“…Recent studies have shown that stimulation of the AT 2 receptor increases the production of bradykinin, PGE 2 and NO, leading to arteriolar vasodilation and suppression of cell growth and proliferation. [40][41][42][43] Therefore, the inability of ARBs to prevent kinin degradation in contradistinction to ACE inhibitors is compensated by their ability to increase kinin production through the AT 2 receptor. Although these actions are shared by all ARBs, telmisartan has the additional advantage of being longer acting and more efficacious with respect to its antihypertensive effects and to effectively suppress the rise of blood pressure during the early hours of the morning when it is needed the most.…”