Human renal and systemic hemodynamic, natriuretic, and neurohumoral responses to different doses of L-NAME

Experimental evidence indicates that the renal circulation is more sensitiv e to the effects of nitric oxide (NO) synthesis inhibition than other vascu lar beds. To explore whether in men the NO-mediated vasodilator tone is gre ater in the renal than in the systemic circulation, the effects of three di fferent intravenous infusions of N-G-nitro-L-arginine methyl ester (L-NAME; 1, 5, and 25 mu g.kg(-1).min(-1) for 30 min) or placebo on mean arterial p ressure (MAP), systemic vascular resistance (SVR), renal blood flow (RBF), renal vascular resistance (RVR), glomerular filtration rate (GFR), and frac tional sodium and lithium excretion (FENa and FELi) were studied in 12 heal thy subjects, each receiving randomly two of the four treatments on two dif ferent occasions. MAP was measured continuously by means of the Finapres de vice, and stroke volume was calculated by a model flow method. GFR and RBF were estimated from the clearances of radiolabeled thalamate and hippuran. Systemic and renal hemodynamics were followed for 2 h after start of infusi ons. During placebo, renal and systemic hemodynamics and FEN, and FELi rema ined stable. With the low and intermediate L-NAME doses, maximal increments in SVR and RVR were similar: 20.4 +/- 19.6 and 23.5 +/- 16.0%, respectivel y, with the low dose and 31.4 +/- 26.7 and 31.2 +/- 14.4%, respectively, wi th the intermediate dose (means +/- SD). With the high L-NAME dose, the inc rement in RVR was greater than the increment in SVR. Despite a decrease in RBF, FEN, and FELi did not change with the low L-NAME dose, but they decrea sed by 31.2 +/- 11.0 and 20.2 +/- 6.3%, respectively, with the intermediate dose and by 70.8 +/- 8.1 and 31.5 +/- 15.9% with the high L-NAME dose, res pectively. It is concluded that in men the renal circulation is not more se nsitive to the effects of NO synthesis inhibition than the systemic circula tion and that the threshold for NO synthesis inhibition to produce antinatr iuresis is higher than the threshold level to cause renal vasoconstriction.