RENAL NITRIC-OXIDE AND ANGIOTENSIN-II INTERACTION IN RENOVASCULAR HYPERTENSION

In two-kidney, one clip (2K1C) renovascular hypertension, blood flow is reduced to the clipped but not to the nonclipped kidney, despite elevated angiotensin II. To determine possible interactions between endothelium-derived nitric oxide and angiotensin, we studied bilateral renal blood flow using radioactive microspheres in anesthetized 2K1C hypertensive rats 4 weeks after clipping. We studied the response to nitric oxide synthesis inhibition with 10 mg/kg body wt N(G)-nitro-L-arginine-methyl ester (L-NAME) in hypertensive rats untreated (n=5) or treated (n=5) with 10 mg/kg body wt of the angiotensin II antagonist losartan. 2K1C rats had a blood pressure of 159 +/- 9 mm Hg, and renal blood flow to the clipped kidney was reduced 87% compared with the nonclipped kidney. L-NAME increased blood pressure 36 +/- 5 mm Hg and decreased renal blood How in the nonclipped kidney 61% (4.9 +/- 0.5 to 1.9 +/- 0.4 mL/min per gram kidney weight, P<.001). Renal vascular resistance increased 200% (33.4 +/- 2.2 to 100.7 +/- 15.0 resistance units [RU], P<.005). Renal blood flow and resistance in the clipped kidney were unchanged by L-NAME. Treatment of 2K1C rats with losartan reduced blood pressure (154 +/- 8 to 116 +/- 11 mm Hg, P<.01), did not change blood flow in the nonclipped, but normalized it in the clipped kidney (4.8 +/- 0.8 mL/min per gram kidney weight). With losartan, L-NAME increased pressure by 38 +/- 10 mm Hg, decreased renal blood flow 10% (5.9 +/- 0.5 to 5.3 +/- 0.3 mL/min per gram kidney weight, P<.05), and increased renal resistance 49% (19.7 +/- 1.2 to 29.4 +/- 2.2 RU, P<.001) in the nonclipped kidney. Neither blood flow nor resistance was changed in the clipped kidney. Our results suggest that nitric oxide maintains renal perfusion of the nonclipped but not the clipped kidney in 2K1C rats. Nitric oxide counteracts elevated angiotensin to regulate perfusion in the nonclipped kidney, but angiotensin vasoconstriction predominates in the clipped kidney. Thus, nitric oxide vasodilation is a regulatory response to maintain contralateral renal perfusion despite elevated angiotensin after renal artery stenosis in 2K1C hypertension.