Modulation of hemodynamics and organ blood flow by nitric oxide synthase inhibition is not altered in normotensive, septic rats.
Hyperdynamic sepsis is associated with a redistribution of organ blood flow. We hypothesized that increased nitric oxide (NO) production could mediate this process. The objective of this study was to determine the effect of a NO synthesis inhibitor on systemic and organ blood flows in vivo in septic and in normal rats. Rats were instrumented for hemodynamic monitoring and randomized to undergo cecal ligation and perforation (CLP) or control laparotomy. Cardiac output and organ blood flow were measured by thermodilution and radioactive microspheres, respectively. Baseline values were obtained at 24 h after CLP or control laparotomy and after the administration of L-nitro-arginine methyl ester (L-NAME) at 2, 4, 8, and 16 mg/kg intravenously. All studies were performed in awake, unrestrained animals. Septic animals were normotensive and hyperdynamic. L-NAME decreased cardiac index and increased systemic vascular resistance and mean arterial blood pressure to an equivalent degree in control and in CLP animals. CLP was associated with significantly increased relative blood flow to the small bowel and portal circulation. Although cardiac output decreased with L-NAME, blood flow to the diaphragm, liver, and brain was relatively well preserved. Absolute blood flow to other organs, including small bowel, decreased in parallel to the cardiac output. The effect of L-NAME on organ blood flow was comparable in control and in CLP animals. We conclude that the influence of NO on organ blood flows appears to vary between organs, but that NO does not explain the redistribution of blood flow observed in hyperdynamic sepsis.
Martin
C M
CM
A.C. Burton Vascular Biology Laboratory, Victoria Hospital, London, Ontario, Canada.
Sibbald
W J
WJ
D000594:Amino Acid Oxidoreductases / Q000037:antagonists & inhibitors*; D000704:Analysis of Variance; D000818:Animals; D001120:Arginine / Q000031:analogs & derivatives / Q000494:pharmacology; D002432:Cecum / Q000503:physiopathology; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D006439:Hemodynamics / Q000187:drug effects / Q000502:physiology; D007421:Intestine, Small / Q000098:blood supply; D008297:Male; D019331:NG-Nitroarginine Methyl Ester; D009569:Nitric Oxide / Q000037:antagonists & inhibitors / Q000502:physiology; D019001:Nitric Oxide Synthase; D011897:Random Allocation; D051381:Rats; D017207:Rats, Sprague-Dawley; D012039:Regional Blood Flow / Q000187:drug effects / Q000502:physiology; D018805:Sepsis / Q000503:physiopathology*; D014851:Wakefulness / Q000187:drug effects / Q000502:physiology
D009569:Nitric Oxide; D001120:Arginine; D019001:Nitric Oxide Synthase; D000594:Amino Acid Oxidoreductases; D019331:NG-Nitroarginine Methyl Ester