title: Human renal and systemic hemodynamic, natriuretic, and neurohumoral responses to different doses of L-NAME.
abstract: 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 infusions of NG-nitro-L-arginine methyl ester (L-NAME; 1, 5, and 25 microg. kg-1. min-1 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 (FENa and FELi) 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 FENa and FELi remained 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%, respectively, with the low dose and 31.4 +/- 26.7 and 31.2 +/- 14.4%, respectively, with the intermediate dose (means +/- SD). With the high L-NAME dose, the increment in RVR was greater than the increment in SVR. Despite a decrease in RBF, FENa and FELi did not change with the low L-NAME dose, but they decreased 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, 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.
authors.affiliation: Department of Internal Medicine I, University Hospital Dijkzigt, 3015 GD Rotterdam, The Netherlands.
authors.forename: A
authors.initials: A
authors.lastname: Broere
authors.forename: A H
authors.initials: AH
authors.lastname: Van Den Meiracker
authors.forename: F
authors.initials: F
authors.lastname: Boomsma
authors.forename: F H
authors.initials: FH
authors.lastname: Derkx
authors.forename: A J
authors.initials: AJ
authors.lastname: Veld
authors.forename: M A
authors.initials: MA
authors.lastname: Schalekamp
mesh_terms: D000328:Adult; D004305:Dose-Response Relationship, Drug; D004791:Enzyme Inhibitors / Q000008:administration & dosage / Q000494:pharmacology*; D006439:Hemodynamics / Q000187:drug effects*; D006801:Humans; D007668:Kidney / Q000378:metabolism; D008297:Male; D019331:NG-Nitroarginine Methyl Ester / Q000008:administration & dosage / Q000494:pharmacology*; D009318:Natriuresis / Q000187:drug effects*; D018377:Neurotransmitter Agents / Q000097:blood*; D012079:Renal Circulation / Q000187:drug effects*; D012964:Sodium / Q000378:metabolism; D014867:Water / Q000378:metabolism
chemical_list: D004791:Enzyme Inhibitors; D018377:Neurotransmitter Agents; D014867:Water; D012964:Sodium; D019331:NG-Nitroarginine Methyl Ester