APStracts 2:0018F, 1995.

Comparison of systemic and direct intrarenal angiotensin ii blockade on sodium excretion in rats. Peng, Yan, and Franklyn G. Knox. Departments of Physiology & Biophysics and Medicine, Mayo Clinic and Foundation, Rochester, MN 55905

APStracts 2:0018F, 1995.

To dissociate the renal effects from the systemic effects of angiotensin II blockade, the present study was designed to determine the effects of systemic and renal interstitial infusion of the specific angiotensin II (AII) receptor antagonist, losartan, on blood pressure and sodium excretion in rats fed a low, normal or high sodium diet. Fractional sodium excretion (FENa) and mean arterial pressure (MAP) were measured in rats before and during systemic infusion of losartan (10mg/kg), or renal interstitial infusion of losartan (3mg/kg), by means of a chronically implanted matrix. In rats fed a low or normal sodium diet, systemic infusion of losartan markedly decreased MAP (_ -21+- 2mmHg, _ -10+- 2mmHg, P<0.05 respectively) with an accompanying fall in FENa (_ -0.10+- 0.05%, _ -0.91+- 0.40%, P<0.05 respectively). In contrast, preferential blockade of renal AII with renal interstitial losartan infusion resulted in an increase in FENa (_ 0.13+- 0.04%, _ 0.95+- 0.45%, P<0.05 respectively), and no significant change in MAP. In rats fed a high sodium diet, both systemic and renal interstitial infusion of losartan increased FENa (_ 1.90+- 0.26%, _ 1.40+- 0.56%, P<0.05 respectively). Although systemic infusion of losartan decreased MAP (_ -4.4+- 0.6mmHg, P<0.05) in rats fed a high sodium diet, the reduction in MAP was much less than that in rats fed a low and normal sodium diet. In conclusion, in rats fed a low or normal sodium diets, systemic AII blockade reduced both arterial blood pressure and sodium excretion, whereas intrarenal AII blockade had no effect on blood pressure and increased sodium excretion. In contrast, both systemic and intrarenal AII blockade increased sodium excretion without marked effects on blood pressure in rats fed a high sodium diet.

Received 5 July 1994; accepted in final form 7 February 1995.
APS Manuscript Number F223-4.
Article publication pending Am. J. Physiol. (Renal Fluid Electrolyte
Physiology).
ISSN 1080-4757 Copyright 1995 The American Physiological Society.
Published in APStracts on 23 February 1995.