Effects of NG-nitro-L-arginine methyl ester on renal function and blood pressure.
The dose-dependent effects of intravenous infusions of nitric oxide (NO) synthesis inhibitor, NG-nitro-L-arginine methyl ester (L-NAME; 0.1, 1, 10, and 50 micrograms.kg-1.min-1), were studied in anesthetized rats to determine whether the inhibitory actions of L-NAME are manifested primarily in alterations of renal function or whether they are the consequences of the increase in systemic blood pressure. Mean arterial pressure (MAP) was not altered by the intravenous L-NAME infusions of 0.1 and 1.0 microgram.kg-1.min-1. However, 0.1 microgram.kg-1.min-1 L-NAME induced a 30% decrease in urine flow rate (UV). The administration of 1.0 microgram.kg-1.min-1 L-NAME, in addition to decreasing UV, also decreased urinary sodium excretion (UNaV) and renal plasma flow (RPF). The intravenous L-NAME infusions of 10.0 and 50.0 microgram.kg-1.min-1 intravenous L-NAME infusions of 10.0 and 50.0 microgram.kg-1.min-1 produced significant increases in MAP that reversed the initial fall in UV and UNaV, despite decreasing RPF and glomerular filtration rate (GFR). The administration of L-arginine alone (10 micrograms.kg-1.min-1) did not modify any of the parameters measured, but it effectively prevented all the hemodynamic and renal changes induced by the infusion of 50 micrograms.kg-1.min-1 L-NAME. These results suggest that the decrease in nitric oxide production induced by the intravenous infusion of L-NAME affects renal excretion of sodium and water in the absence of any significant change in blood pressure. At larger doses, L-NAME also produces hypertension that overrides the initial antinatriuretic effect.
Lahera
V
V
Department of Physiology, Mayo School of Medicine, Rochester, Minnesota 55905.
Salom
M G
MG
Miranda-Guardiola
F
F
Moncada
S
S
Romero
J C
JC
D000818:Animals; D001120:Arginine / Q000031:analogs & derivatives* / Q000494:pharmacology; D001794:Blood Pressure / Q000187:drug effects*; D004231:Diuresis / Q000187:drug effects; D005919:Glomerular Filtration Rate / Q000187:drug effects; D006439:Hemodynamics / Q000187:drug effects; D007668:Kidney / Q000098:blood supply / Q000187:drug effects / Q000502:physiology*; D007700:Kinetics; D019331:NG-Nitroarginine Methyl Ester; D009318:Natriuresis / Q000187:drug effects; D009569:Nitric Oxide / Q000378:metabolism; D051381:Rats; D011919:Rats, Inbred Strains; D012079:Renal Circulation / Q000187:drug effects
D009569:Nitric Oxide; D001120:Arginine; D019331:NG-Nitroarginine Methyl Ester