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

A. Broere, A. H. Van Den Meiracker, F. Boomsma, F. H. M. Derkx, A. J. Man In'T Veld, M. A. D. H. Schalekamp
1998 AJP - Renal Physiology  
Schalekamp. Human renal and systemic hemodynamic, natriuretic, and neurohumoral responses to different doses of L-NAME. Am. J. Physiol. 275 (Renal Physiol. 44): F870-F877, 1998.-Experimental evidence indicates that the renal circulation is more sensitive to the effects of nitric oxide (NO) synthesis inhibition than other vascular beds. To explore whether in men the NO-mediated vasodilator tone is greater in the renal than in the systemic circulation, the effects of three different intravenous
more » ... erent intravenous infusions of N G -nitro-L-arginine methyl ester (L-NAME; 1, 5, and 25 µg · kg Ϫ1 · min Ϫ1 for 30 min) or placebo on mean arterial pressure (MAP), systemic vascular resistance (SVR), renal blood flow (RBF), renal vascular resistance (RVR), glomerular filtration rate (GFR), and fractional sodium and lithium excretion (FE Na and FE Li ) were studied in 12 healthy subjects, each receiving randomly two of the four treatments on two different occasions. MAP was measured continuously by means of the Finapres device, 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 infusions. During placebo, renal and systemic hemodynamics and FE Na and FE Li remained stable. With the low and intermediate L-NAME doses, maximal increments in SVR and RVR were similar: 20.4 Ϯ 19.6 and 23.5 Ϯ 16.0%, respectively, with the low dose and 31.4 Ϯ 26.7 and 31.2 Ϯ 14.4%, respectively, with the intermediate dose (means Ϯ SD). With the high L-NAME dose, the increment in RVR was greater than the increment in SVR. Despite a decrease in RBF, FE Na and FE Li did not change with the low L-NAME dose, but they decreased by 31.2 Ϯ 11.0 and 20.2 Ϯ 6.3%, respectively, with the intermediate dose and by 70.8 Ϯ 8.1 and 31.5 Ϯ 15.9% with the high L-NAME dose, respectively. It is concluded that in men the renal circulation is not more sensitive to the effects of NO synthesis inhibition than the systemic circulation and that the threshold for NO synthesis inhibition to produce antinatriuresis is higher than the threshold level to cause renal vasoconstriction. nitric oxide synthesis inhibition; renal vascular resistance; systemic vascular resistance; fractional sodium excretion; fractional lithium excretion EXPERIMENTAL STUDIES with L-arginine analogs that inhibit nitric oxide (NO) synthesis have provided unequivocal evidence that NO is an important regulator of renal blood flow (RBF), diuresis, and natriuresis. Conse-
doi:10.1152/ajprenal.1998.275.6.f870 fatcat:fvgb7252hrcgllalvl5b67f5zy