Effects of nitric oxide synthase inhibition on regional hemodynamics and oxygen transport in endotoxic dogs.
Nitric oxide synthase (NOS) inhibition has been used to increase blood pressure in humans with septic shock despite a lack of data regarding its effects on O2 delivery (QO2). We studied the effects of NG-nitro-L-arginine methyl ester (L-NAME) on systemic, gut, and hindlimb circulations of endotoxic dogs. Twelve dogs were infused with 2 mg/kg of LPS over 1 h followed by 60 mL/kg of 6% dextran over 2 h. Six dogs also received 20 mg/kg of L-NAME, LPS caused mean arterial pressure (MAP), flow and QO2 to whole body, hindlimb and gut to decrease, but O2 uptake (VO2) did not change. Dextran resuscitation alone produced a hyperdynamic state with increased blood flow to or above baseline. With L-NAME, systemic and regional resistances increased twofold and MAP returned to near baseline. Late in the study, these dogs had significantly lower blood flow and QO2 to the gut but maintained VO2 by increasing oxygen extraction to near critical levels. These data suggest that in acute endotoxicosis, L-NAME may significantly improve blood pressure but may markedly encroach on O2 transport reserves to the gut.
Walker
T A
TA
Department of Pediatrics, University of Alabama at Birmingham 35233, USA.
Curtis
S E
SE
King-VanVlack
C E
CE
Chapler
C K
CK
Vallet
B
B
Cain
S M
SM
D000818:Animals; D001120:Arginine / Q000031:analogs & derivatives* / Q000494:pharmacology; D004285:Dogs; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D005260:Female; D006439:Hemodynamics; D006614:Hindlimb / Q000098:blood supply; D007422:Intestines / Q000098:blood supply* / Q000201:enzymology; D008070:Lipopolysaccharides; D008297:Male; D018482:Muscle, Skeletal / Q000098:blood supply* / Q000201:enzymology; D019331:NG-Nitroarginine Methyl Ester; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors*; D010100:Oxygen / Q000502:physiology; D018805:Sepsis / Q000201:enzymology / Q000503:physiopathology*
D004791:Enzyme Inhibitors; D008070:Lipopolysaccharides; D001120:Arginine; D019001:Nitric Oxide Synthase; D010100:Oxygen; D019331:NG-Nitroarginine Methyl Ester