抄録
To clarify the role of nitric oxide (NO) in the pathogenesis of renovascular hypertension, we examined the effects of long-term oral administration of either the precursor substrate L-arginine or the NO synthesis inhibitor Nω-nitro-L-arginine (L-NA) on systemic and renal hemodynamics in dogs with chronic two-kidney, one-clip (2K-1C) renovascular hypertension. Furthermore, the importance of NO in maintaining kidney function in chronic renal ischemia was evaluated. Chronic inhibition of NO production aggravated the rise in blood pressure (L-NA 117.7±6.8 vs. control 107.2±3.3mmHg, p<0.05 on day 1) and stimulated marked bradycardia (L-NA 84.9±3.2 vs. control 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 vs. control 0.85±0.20ml/min/kg, p<0.01) and glomerular filtration rate (GFR, L-NA 0.02±0.01 vs. 0.22±0.05ml/min/kg, p<0.01) in the ischemic kidney. In contrast, in the contralateral non-clipped kidney, chronic inhibition of NO production induced a significant reduction in RPF with no significant change in GFR. Oral administration of L-arginine had no effect on the magnitude of hypertension. L-arginine significantly improved RPF (2.76±0.49ml/min/kg) and GFR (0.61±0.08ml/min/kg) in the ischemic kidney, whereas the elevation of RPF and GFR in the non-clipped kidney was not significant. Unilateral renal artery occlusion in these hypertensive dogs resulted in diffuse atrophic tubulointerstitial changes in the ischemic kidney. These changes were markedly aggravated by NO synthesis inhibition. On the other hand, L-arginine treatment significantly protected against the morphological changes of renal ischemia. These data show that NO plays a key role in the maintenance of renal function during the evolution of hypertension induced by chronic renal ischemia. In addition, these data demonstrate that renovascular hypertension is associated with a compensatory increase in the vasodilator function of the vascular endothelium. (Hypertens Res 1998; 21: 267-277)
