Change in Pressor Responsiveness to Angiotensin II as a Determinant of Blood Pressure After Unclipping in Two-Kidney, One Clip Hypertensive Rats

Abstract

The hypotensive effect of correction of renal artery stenosis in humans or experimental animals with renovascular hypertension is commonly attributed to decreasing renin secretion from the formerly stenotic kidney. However, plasma renin activity is normal in 50% of individuals with renovascular hypertension. We studied conscious, chronically instrumented two-kidney, one clip (2K1C) rats. The renal artery clip was removed and mean arterial pressure measured for 3 days. The majority of the fall in blood pressure occurred between 2 and 48 hours after unclipping. Measurement of water balance and urinary sodium excretion revealed no effect of unclipping. In another experiment, 2K1C hypertensive rats were chronically treated with enalapril and concomitant infusion of angiotensin II (3.8 pmol/min [4 ng/min] IV) to maintain blood pressure at hypertensive levels and prevent a fall in angiotensin II levels on unclipping. After 5 days, the clip was removed or sham removed, and treatment was continued. Blood pressure was recorded for 7 days. Blood pressure remained elevated in the sham unclipped rats. Unclipped rats exhibited a dichotomous response: blood pressure fell significantly within 48 hours in the majority of rats (responders) but remained elevated in a minority (nonresponders). All treatment was then withdrawn for 2 days. Sham unclipped rats remained hypertensive, and responders exhibited a further small decline in blood pressure. Blood pressure fell to normal in the nonresponders. Blood pressure falls after correction of renal artery stenosis in renovascular hypertension in part because of a decrease in pressor responsiveness to angiotensin II.