Effects of CV-11974 on renal haemodynamics and renal function in dogs

The effects of CV-11974, a nonpeptide angiotensin II (Ang II) receptor antagonist, on renal haemodynamics and function were examined in pentobarbital-anaesthetised dogs to evaluate the physiological role of endogenous Ang II in regulating renal haemodynamics and urine formation. Intrarenal infusion of CV-11974 (1 microgram/kg/min) increased renal blood flow (RBF), glomerular filtration rate (GFR), urine flow, and urinary electrolyte excretion (Na and K), with no change in mean arterial pressure (MAP). In another group of dogs, intrarenal infusion of CV-11974 (1 microgram/kg/min) increased the fractional excretion of sodium, the fractional proximal excretion of sodium, and the fractional distal excretion of sodium. CV-11974 did not affect the linear relationship between the free water reabsorption rate (TCH2O) and osmolar clearance (Cosm). These results suggest that endogenous Ang II may play an important role in regulating renal haemodynamics and stimulating sodium reabsorption. Our data indicates that endogenous Ang II may stimulate sodium reabsorption at the proximal and the distal portions of the tubule, with the exception of the medullary portion of the ascending limb of Henle.