title: Cardiovascular actions of NG-methyl-L-arginine are abolished in a canine shock model using high-dose endotoxin.
abstract: This study was designed to test the hypothesis that endotoxin-induced hypotension is caused, in part, by increased endothelial synthesis of nitric oxide and that inhibition of nitric oxide synthesis with NG-monomethyl-L-arginine (NMA) would reverse the cardiovascular actions of endotoxin. A high dose of endotoxin (1.5 mg/kg, i.v.) was administered by rapid intravenous infusion to pentobarbital-anesthetized dogs. Endotoxin caused rapid and profound reductions in cardiac output and mean arterial pressure; systemic vascular resistance, however, was unaltered except for a transient increase. Coronary and mesenteric blood flows were reduced. NMA (30 mg/kg, i.v.) given 60 min after endotoxin administration, had no significant effect on cardiac function or systemic vascular function except for a transient increase in cardiac output and decrease in systemic vascular resistance. This same dose of NMA given to dogs not receiving endotoxin caused systemic vasoconstriction, increased arterial pressure and decreased cardiac output. These results suggest that increased nitric oxide production is not a primary factor causing endotoxin-induced hypotension and that nitric oxide does not modulate vascular tone following administration of high doses of endotoxin.
authors.affiliation: Department of Pharmacology (D-46R), Abbott Laboratories, Abbott Park, IL 60064.
authors.forename: R E
authors.initials: RE
authors.lastname: Klabunde
authors.forename: M C
authors.initials: MC
authors.lastname: Helgren
mesh_terms: D000818:Animals; D001120:Arginine / Q000031:analogs & derivatives* / Q000494:pharmacology; D001794:Blood Pressure / Q000187:drug effects; D002302:Cardiac Output / Q000187:drug effects; D004195:Disease Models, Animal; D004285:Dogs; D004731:Endotoxins; D004926:Escherichia coli; D006321:Heart / Q000187:drug effects*; D007022:Hypotension / Q000139:chemically induced / Q000378:metabolism; D008070:Lipopolysaccharides; D008297:Male; D009569:Nitric Oxide / Q000378:metabolism; D012769:Shock / Q000139:chemically induced / Q000378:metabolism*; D014655:Vascular Resistance / Q000187:drug effects; D014661:Vasoconstriction / Q000187:drug effects; D019323:omega-N-Methylarginine
chemical_list: D004731:Endotoxins; D008070:Lipopolysaccharides; D019323:omega-N-Methylarginine; D009569:Nitric Oxide; C044101:endotoxin, Escherichia coli; D001120:Arginine