Nakamoto H, Ferrario C M, Buckalew V M, Suzuki H
Department of Nephrology, Saitama Medical School, Japan.
Hypertens Res. 1998 Dec;21(4):267-77. doi: 10.1291/hypres.21.267.
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 Nomega-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 3.3 mmHg, 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+/-0.20 ml/min/kg, p < 0.01) and glomerular filtration rate (GFR, L-NA 0.02+/-0.01 vs. 0.22+/-0.05 ml/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+/-0.49 ml/min/kg) and GFR (0.61+/-0.08 ml/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.
为阐明一氧化氮（NO）在肾血管性高血压发病机制中的作用，我们研究了长期口服前体底物L-精氨酸或NO合成抑制剂Nω-硝基-L-精氨酸（L-NA）对慢性二肾一夹（2K-1C）肾血管性高血压犬全身和肾脏血流动力学的影响。此外，还评估了NO在维持慢性肾缺血时肾功能中的重要性。慢性抑制NO生成会加重血压升高（第1天，L-NA组为117.7±6.8 mmHg，对照组为107.2±3.3 mmHg，p<0.05）并引发明显的心动过缓（第1天，L-NA组为84.9±3.2次/分钟，对照组为94.6±2.6次/分钟，p<0.05）。这些变化与缺血肾脏的肾血浆流量（RPF，L-NA组为0.03±0.02 vs.对照组为0.85±0.20 ml/min/kg，p<0.01）和肾小球滤过率（GFR，L-NA组为0.02±0.01 vs. 0.22±0.05 ml/min/kg，p<0.01）显著降低有关。相反，在对侧未夹闭的肾脏中，慢性抑制NO生成导致RPF显著降低，而GFR无显著变化。口服L-精氨酸对高血压的严重程度无影响。L-精氨酸显著改善了缺血肾脏的RPF（2.76±0.49 ml/min/kg）和GFR（0.61±0.08 ml/min/kg），而未夹闭肾脏中RPF和GFR的升高不显著。这些高血压犬的单侧肾动脉闭塞导致缺血肾脏出现弥漫性萎缩性肾小管间质改变。NO合成抑制显著加重了这些变化。另一方面，L-精氨酸治疗显著预防了肾缺血的形态学改变。这些数据表明，NO在慢性肾缺血诱导的高血压发展过程中对维持肾功能起关键作用。此外，这些数据表明肾血管性高血压与血管内皮舒张功能的代偿性增加有关。
