Renin-angiotensin system modulates renal bradykinin production

Previous studies have shown that sodium depletion is associated with an increase in renal kallikrein-kinin system activity. This system may play an important role in counterbalancing the renal effects of the renin-angiotensin system. In this study, we examined whether the renal renin-angiotensin system participates in the regulation of renal bradykinin (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 arterial 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 (each 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). Glomerular filtration rate and renal plasma flow increased only during losartan 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 failed to change RIF BK, RIF cGMP, urinary cGMP, or urinary PGE(2). These data suggest that the renin-angiotensin system tonically stimulates renal BK production and cGMP formation via a non-AT(1) angiotensin receptor and renal PGE(2) production via the AT(1) receptor.