The subtype-2 (AT(2)) angiotensin receptor regulates renal cyclic guanosine 3',5'-monophosphate and AT(1) receptor-mediated prostaglandin E(2) production in conscious rats

The renal effects of angiotensin II(AII) are attributed to AT(1) receptors. In contrast, the function of renal AT(2) receptorsis unknown. Using a microdialysis technique, we monitored changes in renal interstitial fluid (RIF) prostaglandin E(2) (PGE(2)) and cyclic guanosine 3',5'-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, These data demonstrate that activation of the renin-angiotensin system during Na depletion increases renal interstitial PGE(2) and cGMP, The AT(1) receptor mediates renal production of PGE(2). The AT(2) receptor mediates cGMP. AT(2) blockade potentiates angiotensin-induced PGE(2) production at the AT(1) receptor.