Nitric oxide synthase inhibition reduces venous return in porcine endotoxemia.
Mechanisms of circulatory effects induced by nitric oxide synthase inhibition in endotoxemia were investigated in 36 pigs randomized to 1) endotoxin infusion (1.7 micrograms.kg-1.h-1 iv) for 7 h and bolus NG-nitro-L-arginine methyl ester (L-NAME; 25 mg/kg iv) after 3 h; 2) endotoxin infusion for 7 h; 3) saline infusion for 7 h and L-NAME after 3 h; and 4) saline infusion for 7 h. Fifteen minutes after L-NAME injection during endotoxemia, reductions in cardiac output (41%, P < 0.05), portal venous flow (51%, P < 0.05), and hepatic artery flow (50%, P < 0.05) were observed. Systemic vascular resistance increased by 82% (P < 0.05), and the portocaval vascular resistance increased by 101% (P < 0.05). Despite marked vasoconstriction after L-NAME, left ventricular intracavitary filling pressure, central venous pressure, and arterial pressure remained unchanged. During endotoxemia, hematocrit increased from 38.4 +/- 1.4 to 41.9 +/- 1.2 after L-NAME, and blood volume (n = 3) was reduced by an average of 8.3 ml/kg body wt. These changes probably reflect transcapillary fluid loss as urine output was unchanged. In conclusion, L-NAME decreased intravascular blood volume and increased splanchnic venous resistance. These effects will tend to reduce venous return. Combined with a marked increase in left ventricular after-load, L-NAME may thus compromise cardiovascular function in endotoxemia.
Institute for Surgical Research, National Hospital, Oslo, Norway.
T
T
Saetre
O A
OA
Smiseth
T
T
Scholz
H
H
Carlsen
L
L
Nordsletten
E
E
Fahlstrøm
A O
AO
Aasen
D000818:Animals; D001810:Blood Volume / Q000187:drug effects; D019446:Endotoxemia / Q000201:enzymology* / Q000503:physiopathology*; D004731:Endotoxins / Q000494:pharmacology; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005260:Female; D006400:Hematocrit; D006439:Hemodynamics / Q000187:drug effects; D008102:Liver Circulation / Q000187:drug effects; D008297:Male; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors*; D011168:Portal System / Q000187:drug effects; D013152:Splanchnic Circulation / Q000187:drug effects; D013552:Swine; D014680:Veins / Q000503:physiopathology
D004731:Endotoxins; D004791:Enzyme Inhibitors; D019001:Nitric Oxide Synthase; D019331:NG-Nitroarginine Methyl Ester