EFFECTS OF EXP3174, A NONPEPTIDE ANGIOTENSIN-II RECEPTOR ANTAGONIST, ON RENAL HEMODYNAMICS AND RENAL-FUNCTION IN DOGS

We examined the effects of intrarenal infusion of EXP3174, a non-pepti de angiotensin II receptor antagonist, in order to evaluate the physio logical role of endogenous angiotensin II in regulating renal hemodyna mics and urine formation and to assess the possibility of a tubular si tes (s) of action of endogenous angiotensin II in anesthetized dogs. I ntrarenal infusion of EXP3174 at 15 mug/kg per min caused increases in renal blood flow (RBF), glomerular filtration rate (GFR), urine, flow and urinary electrolyte excretion. The lower dose of EXP3174 (0.5 mug /kg per min) did not change mean arterial pressure, RBF and GFR, but d id increase urine flow. The fractional excretion of sodium, the fracti onal proximal excretion of sodium and the fractional distal excretion of sodium increased with lower doses of EXP3174 infusion. EXP3174 did not affect the linear relationship between the free water reabsorption rate and osmolar clearance. These data suggest that endogenous angiot ensin II plays a significant role in regulating renal hemodynamics and urine formation and endogenous angiotensin II stimulates sodium reabs orption in the proximal and the distal portions of the tubules, with t he exception of the medullary portion of the ascending limb of Henle.