NITRIC-OXIDE SYNTHESIS INHIBITION BLOCKS REVERSAL OF 2-KIDNEY, ONE-CLIP RENOVASCULAR HYPERTENSION AFTER UNCLIPPING

It is well established that two-kidney, one clip renovascular hyperten sion can be rapidly reversed by unclipping. We hypothesized that rapid renal reperfusion and the subsequent fall in blood pressure are media ted in part by nitric oxide, the endothelium-derived relaxing factor. We tested whether the hypotensive response to unclipping could be bloc ked by nitric oxide synthesis inhibition using a bolus of 10 mg/kg bod y wt N-omega-nitro-L-arginine methyl ester. Rats were made hypertensiv e by placing a silver clip on the left renal artery. After 4 weeks, th ey were anesthetized and either not treated (controls) or had nitric o xide synthesis blockade. After 10 minutes, the clip was removed and bl ood pressure monitored over 60 minutes. Initial pressure in controls w as 157+/-8 mm Hg, and heart rate was 310+/-21 beats per minute. Unclip ping resulted in pressure falling to 125+/-6 mm Hg within 45 minutes ( P<.005). Heart rate was unchanged (312+/-9 beats per minute). In contr ast, nitric oxide synthesis inhibition increased blood pressure from 1 49+/-6 to 174+/-9 mm Hg (P<.001). Unclipping did not change blood pres sure, which was 167+/-8 mm Hg after 60 minutes (P<.005 versus controls ), and heart rate remained unchanged (282+/-13 versus 276+/-16 beats p er minute). We determined the blood flow to the clipped kidneys using radioactive microspheres. Unclipping untreated hypertensive rats resul ted in a 10-fold increase in renal blood flow (P<.001), concomitant wi th a decrease in blood pressure. In rats with nitric oxide synthesis i nhibition, unclipping resulted in an increase in renal blood flow that was only a third of that seen in untreated rats, with no change in bl ood pressure. Our results show that nitric oxide synthesis inhibition eliminates the acute reversal of renovascular hypertension caused by u nclipping. This suggests that endothelium-derived nitric oxide may be an important component in the reversal of two-kidney, one clip renovas cular hypertension, either by facilitating renal reperfusion or by med iating the systemic response secondary to renal reperfusion.