DEGREE OF RENAL-ARTERY STENOSIS ALTERS NITRIC-OXIDE REGULATION OF RENAL HEMODYNAMICS

Endothelium-derived nitric oxide (EDNO) maintains RBF in normal kidney s and to the nonclipped kidney of two-kidney, one-clip (2K,1C) renovas cular hypertensive rats. However, in clipped kidneys with severe renal stenosis, EDNO has been reported not to influence RBF, and it was sug gested that low perfusion diminishes the stimulus of shear stress for EDNO synthesis. It was hypothesized that lesser degrees of renal arter y stenosis would allow greater renal perfusion and, hence, a greater r ole for EDNO in maintaining RBF in the clipped kidney. The renal respo nse to EDNO synthesis inhibition was studied with 10 mg/kg body wt N-o mega-nitro-L-arginine methyl ester (L-NAME). Four weeks after clipping , rats had different degrees of (functional) renal artery stenosis as determined by the ratio (R) of RBF (per gram kidney weight) in the non clipped to clipped kidney. Stenosis was Classified as either mild (R l ess than or equal to 1.25) or moderate (R greater than or equal to 1.3 0). Both groups were similarly hypertensive (146 +/- 3 versus 148 +/- 6 mm Hg, respectively) and responded to L-NAME with a 42 mm Hg rise in blood pressure. In 2K,1C rats with mild renal artery stenosis, the re nal response to L-NAME was similar in both nonclipped and clipped kidn eys. RBF decreased by 17 to 19% (P < 0.005) and renal vascular resista nce (RVR) increased by 59 to 63% (P < 0.005). When renal perfusion pre ssure was controlled, the decrease in RBF was exaggerated 3.6-fold in the nonclipped but only 2.3-fold in the clipped kidney, whereas the RV R increased proportionally. In rats with moderate renal stenosis, L-NA ME decreased RBF to the nonclipped kidney by 22% (P < 0.01) and increa sed RVR by 78% (P < 0.005). However, in the clipped kidney, RBF increa sed by 51% (P < 0.02), whereas RVR did not change. When renal perfusio n pressure was controlled, RBF fell in both kidneys, by 52% in the non clipped but by only 15% in the clipped kidney. The RVR increased by 13 8 and 21%, respectively. These results suggest that, in 2K,1C rats wit h only mild stenosis, EDNO is an important regulator of renal perfusio n. However, as the apparent degree of renal artery stenosis increases, the influence of EDNO on renal perfusion is diminished.