Schlaich Markus P, Schmitt Dominik, Ott Christian, Schmidt Bernhard Mw, Schmieder Roland E
Neurovascular Hypertension and Kidney Disease Laboratory, Baker Heart Research Institute, Melbourne, Victoria, Australia.
J Hypertens. 2008 Jan;26(1):110-6. doi: 10.1097/HJH.0b013e3282f1a93e.
Experimental data suggest that increased nitric oxide synthase (NOS) activity contributes to preglomerular vasodilation and subsequent glomerular hyperfiltration. Whether such a relationship also exists in the human renal vasculature has not yet been adequately determined.
We assessed systemic, renal, and intragomerular haemodynamics in 310 subjects with normal renal function [glomerular filtration rate (GFR) > 60 ml/min per 1.73 m], before and after NOS inhibition with L-Nmonomethyl arginine (L-NMMA). Subjects were arbitrarily divided into tertiles according to their basal NOS activity, as assessed by the decrease in renal plasma flow in response to L-NMMA (high -23.4 +/- 8.1 versus medium -10.8 +/- 2.2 versus low -1.0 +/- 4.8%). Resting GFR differed significantly between tertiles: high 114 +/- 21 versus medium 109 +/- 19 versus low 104 +/- 21 ml/min per 1.73 m; analysis of variance P = 0.003. In a multiple stepwise regression analysis, basal NOS activity was the major factor to explain resting GFR (beta = -0.344; P < 0.001). Body weight (beta = -0.295; P < 0.001) and age (beta = -0.164; P < 0.001) emerged as additional factors, whereas body mass index and blood pressure did not enter the final model. The close relationship between resting GFR and basal NOS activity was also mirrored in the renal microcirculation, as demonstrated by an exaggerated effect of L-NMMA on the increase in arteriolar resistance, particularly that of the afferent (RA) arteriole, with higher basal nitric oxide (NO) activity (RA: high +1542 +/- 1065 versus medium +1024 +/- 718 versus low +675 +/- 861 dyne/s per cm; P < 0.001).
Our data clearly support experimental evidence linking NOS activity with increased glomerular filtration, and suggest that basal NO activity is also a major determinant of glomerular haemodynamics in the human renal vasculature.
实验数据表明，一氧化氮合酶（NOS）活性增加会导致肾小体前血管舒张及随后的肾小球超滤。这种关系在人类肾血管系统中是否也存在尚未得到充分确定。
我们评估了310名肾功能正常[肾小球滤过率（GFR）>60 ml/min per 1.73 m²]受试者在使用L- N-甲基精氨酸（L-NMMA）抑制NOS前后的全身、肾脏及肾小球内血流动力学。根据对L-NMMA反应时肾血浆流量的降低情况（高-23.4±8.1%对中-10.8±2.2%对低-1.0±4.8%），将受试者任意分为三分位数。三分位数之间的静息GFR有显著差异：高114±21对中109±19对低104±21 ml/min per 1.73 m²；方差分析P = 0.003。在多元逐步回归分析中，基础NOS活性是解释静息GFR的主要因素（β=-0.344；P<0.001）。体重（β=-0.295；P<0.001）和年龄（β=-0.164；P<0.001）是另外的因素，而体重指数和血压未进入最终模型。静息GFR与基础NOS活性之间的密切关系在肾微循环中也有体现，如L-NMMA对小动脉阻力增加的影响更为显著，尤其是入球（RA）小动脉，基础一氧化氮（NO）活性越高（RA：高+1542±1065对中+1024±718对低+6
