Effects of SQ 20,881 on the intact kidney of dogs with two-kidney, one clip hypertension.

Abstract

In 2 kidney, 1 clip hypertension, the unclamped kidney (UK) actively contributes to hypertension by reducing its excretory ability in response to increased levels of circulating angiotensin II. By exteriorizing the ureter to the dog''s flank several weeks beforehand, renal function was measured directly from the UK of 6 chronic renal hypertensive (> 3 wk) and 6 normal dogs (ND). Mean blood pressure (indwelling catheter) and renal function were measured in the trained dogs for two 20-min periods before and during a 40 min i.v. infusion of SQ 20,881 at a dose (300 .mu.g/kg + 3 .mu.g/kg per min) that caused no changes in blood pressure (BP). In dogs with chronic renal hypertension [121 mm Hg .+-. 2 SE] and mild elevation of plasma renin activity (2.0 .+-. 0.4 vs. 0.4 .+-. 0.1 ng/ml per in ND) infusion of SQ 20,881 caused marked increases in Na excretion (UNaV), glomerular filtration rate and effective renal plasma flow. The changes in UNaV and effective renal plasma flow were highly correlated (r = 0.77, P < 0.001). In normotensive dogs (99 .+-. 2 mm Hg) SQ 20,881 caused a 30% .+-. 5% rise in UNaV, a modest increase in glomerular filtration rate (4% .+-. 2%) and no change in effective renal plasma flow. Infusion of a mild pressor dose of angiotensin II (4 ng/kg per min) produced decreases in Na excretion, effective renal plasma flow and glomerular filtration rate in the normotensive dogs. In the hypertensive animals, the same infusion rate of angiotensin II caused significant natriuresis without changes in effective renal plasma flow and glomerular filtration rate. Mild increases in plasma renin activity associated with the chronic phase of 2-kidney, 1 clip hypertension contribute in modifying the renal function of the untouched kidney.