Differential hemodynamic effects of L-NMMA in endotoxemic and normal dogs.
We studied the differential hemodynamic effects of N omega-monomethyl-L-arginine (L-NMMA), an inhibitor of nitric oxide (NO) synthesis, in normal and endotoxemic dogs and examined its activity across the venous, pulmonary, and systemic circulations. Survival was used to determine therapeutic efficacy. In both normal and endotoxemic animals, L-NMMA similarly increased systemic (P = 0.01) and pulmonary (P = 0.047) vascular resistance, marginally increased mean arterial pressure (P = 0.07), and decreased oxygen delivery (P = 0.01) compared with normal saline. In contrast, the effect of L-NMMA on mean pulmonary arterial pressure, central venous pressure, and pulmonary capillary wedge pressure was different in endotoxemic than in normal animals (P < 0.05), but this differential effect occurred > 6 h after endotoxin challenge. L-NMMA (1-10 mg.kg-1.h-1) did not significantly increase survival rates or times in endotoxemic animals, but the highest dose decreased survival times (P < 0.05). Thus the effect of L-NMMA was similar on the systemic arterial circulation in endotoxemic dogs compared with normal dogs but was increased in the venous and pulmonary vascular beds after endotoxin, suggesting that the induction of NO production was greater in low-resistance vessels. We were unable to show that nonselective inhibition of NO production was beneficial in endotoxemic dogs.
Cobb
J P
JP
Critical Care Medicine Department, Warren G. Magnuson Clinical Center, National Institutes of Health, Bethesda, Maryland 20892, USA.
Natanson
C
C
Quezado
Z M
ZM
Hoffman
W D
WD
Koev
C A
CA
Banks
S
S
Correa
R
R
Levi
R
R
Elin
R J
RJ
Hosseini
J M
JM
D000818:Animals; D001120:Arginine / Q000031:analogs & derivatives* / Q000494:pharmacology; D004285:Dogs; D004731:Endotoxins / Q000097:blood* / Q000494:pharmacology; D006439:Hemodynamics / Q000187:drug effects*; D009569:Nitric Oxide / Q000037:antagonists & inhibitors; D012016:Reference Values; D012772:Shock, Septic / Q000401:mortality / Q000503:physiopathology; D019323:omega-N-Methylarginine
D004731:Endotoxins; D019323:omega-N-Methylarginine; D009569:Nitric Oxide; D001120:Arginine