title: The effects of nitric oxide inhibition on regional hemodynamics during hyperdynamic endotoxemia.
abstract: OBJECTIVE
  To determine the effect of the inhibition of nitric oxide (NO) on selective organ blood flow in endotoxin-induced sepsis.
  
  
  METHODS
  Nonrandomized, controlled experiment.
  
  
  METHODS
  Animal research facility in Brooklyn, NY.
  
  
  METHODS
  Eleven mongrel dogs.
  
  
  METHODS
  Eleven dogs were divided into one of two groups: a control group (n = 5) and an endotoxin-treated group (n = 6). The animals were anesthetized, and electromagnetic and ultrasonic flow probes were placed on the distal aorta, right internal carotid artery, superior mesenteric artery, and left renal artery. Sepsis was induced with a 60-mg/kg intravenous injection of Escherichia coli endotoxin. When the arterial blood pressure decreased to less than 60 mm Hg despite adequate fluid resuscitation, NO synthesis was inhibited with a 25-mg/kg intravenous administration of NG-monomethyl-L-arginine. After 15 minutes of inhibition, a 400-mg/kg intravenous administration of L-arginine, the substrate of NO synthase enzyme, was given. Physiologic measurements were continued for 15 minutes thereafter.
  
  
  METHODS
  Heart rate, blood pressure, central venous pressure, pulmonary artery pressure, pulmonary capillary wedge pressure, cardiac output, hematocrit, arterial and venous blood gas values, and blood flow measurements of right internal carotid artery, superior mesenteric artery, left renal artery, and distal aorta.
  
  
  RESULTS
  Control animals did not demonstrate a significant (P > .05) decrease in blood flow in the internal carotid artery, superior mesenteric artery, and distal aorta after the administration of NG-monomethyl-L-arginine. The endotoxin-treated group showed a significant (P < .05) decrease in organ perfusion when treated with the NO synthase inhibitor, NG-monomethyl-L-arginine.
  
  
  CONCLUSIONS
  Inhibition of NO production in the treatment of sepsis caused a significant decrease in blood flow to all vascular beds in vivo. The role, if any, of the inhibition of NO in the treatment of sepsis is questioned.
authors.affiliation: Department of Surgical Research, Maimonides Medical Center, Brooklyn, NY.
authors.forename: J L
authors.initials: JL
authors.lastname: Henderson
authors.forename: R
authors.initials: R
authors.lastname: Statman
authors.forename: J N
authors.initials: JN
authors.lastname: Cunningham
authors.forename: W
authors.initials: W
authors.lastname: Cheng
authors.forename: P
authors.initials: P
authors.lastname: Damiani
authors.forename: A
authors.initials: A
authors.lastname: Siconolfi
authors.forename: J H
authors.initials: JH
authors.lastname: Horovitz
mesh_terms: D000594:Amino Acid Oxidoreductases / Q000494:pharmacology / Q000627:therapeutic use*; D000818:Animals; D001120:Arginine / Q000031:analogs & derivatives* / Q000494:pharmacology / Q000627:therapeutic use; D016470:Bacteremia / Q000097:blood / Q000188:drug therapy* / Q000503:physiopathology; D001784:Blood Gas Analysis; D004195:Disease Models, Animal; D004285:Dogs; D004353:Drug Evaluation, Preclinical; D004927:Escherichia coli Infections / Q000097:blood / Q000188:drug therapy* / Q000503:physiopathology; D006439:Hemodynamics / Q000187:drug effects*; D009252:NADPH Dehydrogenase / Q000494:pharmacology / Q000627:therapeutic use*; D009569:Nitric Oxide / Q000037:antagonists & inhibitors* / Q000502:physiology; D019001:Nitric Oxide Synthase; D018805:Sepsis / Q000097:blood / Q000188:drug therapy* / Q000503:physiopathology; D019323:omega-N-Methylarginine
chemical_list: D019323:omega-N-Methylarginine; D009569:Nitric Oxide; D001120:Arginine; D019001:Nitric Oxide Synthase; D000594:Amino Acid Oxidoreductases; D009252:NADPH Dehydrogenase