INFLUENCE OF NITRIC-OXIDE IN THE CHRONIC PHASE OF 2-KIDNEY, ONE-CLIP RENOVASCULAR HYPERTENSION

Chronic two-kidney, one clip (2K1C) renovascular hypertension is chara cterized by a largely angiotensin-independent elevated blood pressure (BP). We hypothesized that the long-term effect of hypertension would compromise endothelium-derived nitric oxide (NO) and diminish its infl uence in controlling renal perfusion. We determined the influence of e ndothelium-derived NO on renal hemodynamics and the angiotensin-NO int eraction regulation of renal perfusion in rats with chronic 2K1C hyper tension. Renal blood now (RBF) was measured by radioactive microsphere s in rats with either early-phase (4 weeks after clipping, n=7) or chr onic-phase (13 to 16 weeks after clipping, n=7) 2K1C hypertension. The systemic and renal response to NO synthesis inhibition was determined with 10 mg/kg body wt N-omega-nitro-L-arginine methyl ester (L-NAME). In rats with early-phase 2K1C hypertension BP was 149+/-3 nlm Hg, whi ch increased by 42+/-3 mm Hg with L-NAME (P<.001). L-NAME decreased RB F by 20% (P<.02) and 17% (P<.005) and increased renal vascular resista nce (RVR) by 58% (P<.005) and 62%(P<.02) in the nonclipped and clipped kidneys, respectively. In rats with chronic 2K1C hypertension, BP was 166+/-3 mm Hg, and L-NAME increased this by 35+/-6 mm Hg (P<.001). In the nonclipped and clipped kidneys of chronic 2K1C hypertensive rats, L-NAME decreased RBF by 20% (P<.01) and 17% (P<.01) and increased RVR by 51% (P<.005) and 60% (P<.02), respectively. There were no differen ces in L-NAME-induced changes between early-and chronic-phase 2K1C hyp ertensive rats. Next, we treated seven chronic-phase 2K1C hypertensive rats with 10 mg/kg body wt losartan, which reduced BP by only 7.7% (P <.005). After losartan, L-NAME increased BP by 41+/-3 mm Hg (P<.001), decreased RBF to the nonclipped kidney by 44% (P<.05), and increased R VR by 110% (P<.005); the decrease in RBF was significantly greater com pared with untreated chronic-phase controls (P<.05). In the clipped ki dney, L-NAME: decreased RBF by 26% (P<.05) and increased RVR by 76% (P <.05). Thus, angiotensin blockade did not attenuate the systemic or re nal vasoconstriction to L-NAME. Our results suggest that in both early and chronic phases of 2K1C hypertension, NO contributes significant d ilator tone to buffer the hypertension and maintains perfusion of both kidneys by counterbalancing angiotensin-independent vasoconstriction.