RENIN-ANGIOTENSIN SYSTEM MODULATES RENAL BRADYKININ PRODUCTION

Previous studies have shown that sodium depletion is associated with a n increase in renal kallikrein-kinin system activity. This system may play an important role in counterbalancing the renal effects of the re nin-angiotensin system. In this study, we examined whether the renal r enin-angiotensin system participates in the regulation of renal bradyk inin (BK) levels during sodium depletion. We measured changes in renal excretory and hemodynamic function, renal interstitial fluid (RIF) BK , and RIF and urinary guanosine 3',5'-cyclic monophosphate (cGMP) and prostaglandin E(2) (PGE(2)) in conscious uninephrectomized dogs (n = 5 ) in sodium metabolic balance (10 meq/day) in response to intrarenal a rterial administration of the renin inhibitor ACRIP (0.2 mu g . kg(-1) . min(-1)) or angiotensin II AT(1)-receptor blocker losartan (100 ng . kg(-1). min(-1)). ACRIP and losartan increased urine flow rate from 0 .75 +/- 0.06 to 1.6 +/- 0.03 and 1.5 +/- 0.05 ml/min, respectively (ea ch P < 0.001), and urine sodium excretion from 5.4 +/- 0.7 to 18.3 +/- 1.3 and 15.9 +/- 1.2 meq/min, respectively (each P < 0.001). Glomerul ar filtration rate and renal plasma flow increased only during losarta n administration (P < 0.05). ACRIP decreased RIF BK by 48%, from 33.1 +/- 3.8 to 17.4 +/- 4.1 pg/min (P < 0.01). ACRIP decreased RIF cGMP by 38%, from 0.69 +/- 0.08 to 0.43 +/- 0.1 pmol/min (P < 0.01); urinary cGMP by 16%, from 0.63 +/- 0.05 to 0.53 +/- 0.02 pmol/min (P < 0.05); and RIF PGE(2) by 46%, from 10.5 +/- 1.1 to 5.7 +/- 1.1 pg/min (P < 0. 01). Urinary PGE(2) was unchanged by ACRIP. Losartan decreased RIF PGE (2) by 71%, from 10.8 +/- 0.6 to 3.1 +/- 0.6 pg/min (P < 0.01) but fai led to change RIF BK, RIF cGMP, urinary cGMP, or urinary PGE(2). These data suggest that the renin-angiotensin system tonically stimulates r enal BK production and cGMP formation via a non-AT(1) angiotensin rece ptor and renal PGE(2) production via the AT(1) receptor.