Role of nitric oxide in the evolution of renal ischemia in two-kidney, one-clip renovascular hypertension

To clarify the role of nitric oxide (NO) in the pathogenesis of renovascula r hypertension, we examined the effects of long-term oral administration of either the precursor substrate L-arginine or the NO synthesis inhibitor N- omega-nitro-L-arginine (L-NA) on systemic and renal hemodynamics in dogs wi th chronic two-kidney, one-clip (2K-1C) renovascular hypertension. Furtherm ore, the importance of NO in maintaining kidney function in chronic renal i schemia was evaluated. Chronic inhibition of NO production aggravated the r ise in blood pressure (L-NA 117.7 +/- 6.8 vs. control 107.2+/-3.3 mmHg, p < 0.05 on day 1) and stimulated marked bradycardia (L-NA 84.9+/-3.2 cu. cont rol 94.6+/-2.6 beats/min, p < 0.05 on day 1). These changes were associated with significant reductions in renal plasma flow (RPF, L-NA 0.03+/-0.02 us . control 0.85+/-0.20 ml/min/kg, p < 0.01) and glomerular filtration rate ( GFR, L-NA 0.02+/-0.01 cs, 0.22 +/- 0.05 ml/min/kg, p < 0.01) in the ischemi c kidney. In contrast, in the contralateral non-clipped kidney, chronic inh ibition of NO production induced a significant reduction in RPF with no sig nificant change in GFR, Oral administration of L-arginine had no effect on the magnitude of hypertension, L-arginine significantly improved RPF (2.76 +/- 0.49 ml/min/kg) and GFR (0.61 +/- 0.08 ml/min/kg) in the ischemic kidne y, whereas the elevation of RPF and GFR in the non-clipped kidney was not s ignificant. Unilateral renal artery occlusion in these hypertensive dogs re sulted in diffuse atrophic tubulointerstitial changes in the ischemic kidne y, These changes were markedly aggravated by NO synthesis inhibition. On th e other hand, L-arginine treatment significantly protected against the morp hological changes of renal ischemia. These data show that NO plays a key ro le in the maintenance of renal function during the evolution of hypertensio n induced by chronic renal ischemia. In addition, these data demonstrate th at renovascular hypertension is associated with a compensatory increase in the vasodilator function of the vascular endothelium.