Dedeoglu I O, Springate J E
Department of Pediatrics, State University of New York at Buffalo School of Medicine, The Children's Hospital, 14222, USA.
Clin Exp Hypertens. 2001 Apr;23(3):267-75. doi: 10.1081/ceh-100102665.
We examined the effect of acute systemic blockade of nitric oxide (NO) synthesis on blood pressure and renal function in rats with angiotensin II dependent two-kidney, one-clip Goldblatt hypertension. Hypertensive animals had significantly higher blood pressures, plasma NO metabolite concentrations and urinary NO metabolite excretion rates than control rats. Intravenous administration of N(G)-nitro-L-arginine methylester (L-NAME) (10 mg/kg) increased mean arterial pressure in both hypertensive and control animals with the magnitude of increase being greater in hypertensive than control rats (32 +/- 3 vs. 20 +/- 2 mmHg, p < 0.05). L-NAME did not affect glomerular filtration rates of normal and clipped kidneys but significantly decreased non-clipped kidney glomerular filtration rate (1.1 +/- 0.1 vs. 0.7 +/- 0.1 ml/min per g kidney wt, p < 0.05). Blood flow to normal and non-clipped kidneys fell in response to L-NAME. Percent reduction in renal blood flow produced by L-NAME was significantly greater in non-clipped than normal kidneys (38 +/- 3 vs. 24 +/- 2%, p < 0.05). In contrast, clipped kidney blood flow increased after L-NAME (3.3 +/- 0.2 vs. 4.0 +/- 0.2 ml/min per g kidney wt, p < 0.05). An identical improvement in clipped kidney blood flow occurred when arterial pressure was raised with aortic constriction indicating that the systemic pressor effect of L-NAME was responsible for this finding. These results indicate that NO plays an important role in systemic and non-clipped kidney hemodynamics in renovascular hypertension. Because NO has little influence on stenotic kidney function, the stimulus for increased NO system activity in this disease appears to be vascular shear stress rather than elevated circulating or intrarenal angiotensin II concentrations.
我们研究了急性系统性一氧化氮（NO）合成阻断对血管紧张素II依赖性两肾一夹型Goldblatt高血压大鼠血压和肾功能的影响。高血压动物的血压、血浆NO代谢物浓度和尿NO代谢物排泄率均显著高于对照大鼠。静脉注射N(G)-硝基-L-精氨酸甲酯（L-NAME）（10mg/kg）可使高血压和对照动物的平均动脉压升高，且高血压大鼠的升高幅度大于对照大鼠（32±3 vs. 20±2 mmHg，p<0.05）。L-NAME不影响正常肾和夹闭肾的肾小球滤过率，但显著降低非夹闭肾的肾小球滤过率（1.1±0.1 vs. 0.7±0.1 ml/min per g肾重，p<0.05）。L-NAME使正常肾和非夹闭肾的血流减少。L-NAME引起的肾血流减少百分比在非夹闭肾中显著大于正常肾（38±3 vs. 24±2%，p<0.05）。相反，L-NAME注射后夹闭肾血流增加（3.3±0.2 vs. 4.0±0.2 ml/min per g肾重，p<0.05）。当通过主动脉缩窄使动脉压升高时，夹闭肾血流出现相同程度的改善，表明L-NAME的全身升压作用是导致这一结果的原因。这些结果表明，NO在肾血管性高血压的全身和非夹闭肾血流动力学中起重要作用。由于NO对狭窄肾的功能影响较小，该疾病中NO系统活性增加的刺激因素似乎是血管剪切应力，而非循环或肾内血管紧张素II浓度升高。
