多巴胺-2受体阻断增强了一氧化氮抑制对人体肾脏的影响。

Montanari A, Tateo E, Fasoli E, Donatini A, Cimolato B, Perinotto P, Dall'Aglio P

Istituto di Patologia Medica, University of Parma, Italy.

Hypertension. 1998 Jan;31(1 Pt 2):277-82. doi: 10.1161/01.hyp.31.1.277.

In eight young healthy subjects on a 240 mM Na diet mean arterial pressure (MAP), renal hemodynamics and renal handling of Na and exogenous Li were measured at baseline and during acute nitric oxide (NO) inhibition with 90-minute infusion of 3.0 microg/kg x min(-1) of N(G)-L-arginine methyl ester (L-NAME). The same experiment was repeated with infusion of 50 microg/kg x min(-1) of DA2 receptor blocker L-Sulpiride (L-SULP) alone and, finally, with simultaneous infusion of both L-NAME and L-SULP. L-SULP alone did not elicit any effect. L-NAME alone produced no changes in MAP from 0 to 45 minutes (P1) and a 6.6% increase at 45 to 90 minutes (P2) of infusion. Effective renal plasma flow (ERPF, PAH clearance) and glomerular filtration rate (GFR, inulin clearance) declined by 10.2% and 7.6%, respectively, in P1 and by 15.3% and 11.5% in P2. Filtration Fraction (FF) rose by 4.2% in P2. Calculated renal vascular resistance (RVR) increased by 13.0% to 25.6%. Fractional excretion of Na (FENa) and Li (FELi) fell by 20.0% and by 16.0%, respectively, in P1 and by 40.0% and 25.1% in P2. All these variations, except for MAP and GFR, were significantly greater during coinfusion of L-NAME and L-SULP. ERPF declined by 17.8% to 33.7%, FENa by 26.7% to 53.3%, FELi by 13.8% to 34.8%, while RVR rose by 22.5% to 59.1% and FF by 10.1% to 29.3%. The present data confirm that NO blockade with low-dose systemic infusion of L-NAME produces renal vasoconstriction, reduced GFR with slight increase in FF, and enhanced tubular Li, and Na reabsorption. Since increase in RVR and FF and decrease in FENa and FELi are markedly potentiated by the simultaneous infusion of DA2 blocker L-SULP, which exerts no effects by itself, we suggest that DA interactions between DA system at the level of DA2 receptors and basal NO production play a physiological role in the regulation of renal function in humans.

在8名食用240 mM钠饮食的年轻健康受试者中，在基线时以及在以3.0微克/千克×分钟⁻¹的剂量静脉输注N(G)-L-精氨酸甲酯（L-NAME）90分钟以急性抑制一氧化氮（NO）期间，测量了平均动脉压（MAP）、肾血流动力学以及钠和外源性锂的肾脏处理情况。单独静脉输注50微克/千克×分钟⁻¹的DA2受体阻滞剂L-舒必利（L-SULP）重复相同实验，最后，同时静脉输注L-NAME和L-SULP。单独使用L-SULP未产生任何影响。单独使用L-NAME在输注0至45分钟（P1）时MAP无变化，在输注45至90分钟（P2）时MAP升高6.6%。有效肾血浆流量（ERPF，对氨基马尿酸清除率）和肾小球滤过率（GFR，菊粉清除率）在P1时分别下降10.2%和7.6%，在P2时分别下降15.3%和11.5%。滤过分数（FF）在P2时升高4.2%。计算得出的肾血管阻力（RVR）增加13.0%至25.6%。钠（FENa）和锂（FELi）的分数排泄在P1时分别下降20.0%和16.0%，在P2时分别下降40.0%和25.1%。除MAP和GFR外，所有这些变化在同时输注L-NAME和L-SULP时均显著更大。ERPF下降17.8%至33.7%，FENa下降26.7%至53.3%，FELi下降13.8%至34.8%，而RVR升高22.5%至59.1%，FF升高10.1%至29.3%。目前的数据证实，低剂量全身输注L-NAME阻断NO会导致肾血管收缩、GFR降低且FF略有升高，并增强肾小管对锂和钠的重吸收。由于同时输注自身无作用的DA2阻滞剂L-SULP会显著增强RVR和FF的升高以及FENa和FELi的降低，我们认为DA系统在DA2受体水平与基础NO产生之间的相互作用在人类肾功能调节中发挥生理作用。