Nitric Oxide Synthesis Inhibition Blocks Reversal of Two-Kidney, One Clip Renovascular Hypertension After Unclipping

Abstract

Abstract It is well established that two-kidney, one clip renovascular hypertension can be rapidly reversed by unclipping. We hypothesized that rapid renal reperfusion and the subsequent fall in blood pressure are mediated in part by nitric oxide, the endothelium-derived relaxing factor. We tested whether the hypotensive response to unclipping could be blocked by nitric oxide synthesis inhibition using a bolus of 10 mg/kg body wt N ω -nitro- l -arginine methyl ester. Rats were made hypertensive by placing a silver clip on the left renal artery. After 4 weeks, they were anesthetized and either not treated (controls) or had nitric oxide synthesis blockade. After 10 minutes, the clip was removed and blood pressure monitored over 60 minutes. Initial pressure in controls was 157±8 mm Hg, and heart rate was 310±21 beats per minute. Unclipping resulted in pressure falling to 125±6 mm Hg within 45 minutes ( P <.005). Heart rate was unchanged (312±9 beats per minute). In contrast, nitric oxide synthesis inhibition increased blood pressure from 149±6 to 174±9 mm Hg ( P <.001). Unclipping did not change blood pressure, which was 167±8 mm Hg after 60 minutes ( P <.005 versus controls), and heart rate remained unchanged (282±13 versus 276±16 beats per minute). We determined the blood flow to the clipped kidneys using radioactive microspheres. Unclipping untreated hypertensive rats resulted in a 10-fold increase in renal blood flow ( P <.001), concomitant with a decrease in blood pressure. In rats with nitric oxide synthesis inhibition, unclipping resulted in an increase in renal blood flow that was only a third of that seen in untreated rats, with no change in blood pressure. Our results show that nitric oxide synthesis inhibition eliminates the acute reversal of renovascular hypertension caused by unclipping. This suggests that endothelium-derived nitric oxide may be an important component in the reversal of two-kidney, one clip renovascular hypertension, either by facilitating renal reperfusion or by mediating the systemic response secondary to renal reperfusion.