THE RENIN-ANGIOTENSIN SYSTEM MODULATES RENAL BRADYKININ PRODUCTION. Siragy, Helmy M., Ayad A. Jaffa, Harry S. Margolius, Robert M. Carey. Department of Medicine, University of Virginia Health Sciences Center, Charlottesville, VA 22908 and the Department of Pharmacology, Medical University of South Carolina, Charleston, SC 29425.
APStracts 3:0177R, 1996.
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 counter-balancing 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 levels during sodium depletion. We measured changes in renal excretory and hemodynamic function, renal interstitial fluid (RIF) bradykinin (RIFBK), and RIF and urinary (U) cyclic guanosine monophosphate (cGMP) and prostaglandin-E2 (PGE2) 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 æg/kg/min) or angiotensin II AT1 receptor blocker, losartan (100 ng/kg/min). ACRIP and losartan increased urine flow rate (V) from 0.75 ñ 0.06 to 1.6 ñ 0.03 and 1.5 ñ 0.05 ml/min, respectively (each P<0.001) and urine sodium excretion (UNaV) from 5.4 ñ 0.7 to 18.3 ñ 1.3 and 15.9 ñ 1.2 meq/min, respectively (each P<0.001). Glomerular filtration rate (GFR) and renal plasma flow (RPF) increased only during losartan administration (P<0.05). ACRIP decreased RIFBK by 48% from 33.1 ñ 3.8 to 17.4 ñ 4.1 pg/min (P<0.01). ACRIP decreased RIFcGMP by 38% from 0.69 ñ 0.08 to 0.43 ñ 0.1 pmol/min (P<0.01), UcGMP by 16% from 0.63 ñ 0.05 to 0.53 ñ 0.02 pmol/min (P<0.05), and RIFPGE2 by 46% from 10.5 ñ 1.1 to 5.7 ñ 1.1 pg/min (P<0.01). UPGE2 was unchanged by ACRIP. Losartan decreased RIFPGE2 by 71% from 10.8 ñ 0.6 to 3.1 ñ 0.6 pg/min (P<0.01) but failed to change RIFBK, RIFcGMP, UcGMP or UPGE2. These data suggest that the renin-angiotensin system tonically stimulates renal bradykinin production and cGMP formation via a non-AT1 angiotensin receptor and renal PGE2 production via the AT1 receptor. 

Received 7 February 1996; accepted in final form 2 February 1996.
APS Manuscript Number R78-6.
Article publication pending Am. J. Physiol. (Regulatory Physiology).
ISSN 1080-4757 Copyright 1996 The American Physiological Society.
Published in APStracts on 19 May 96