Effects of N-methyl-L-arginine on cardiac and regional blood flow in a dog endotoxin shock model.
OBJECTIVE
Indirect evidence suggests a decrease in organ perfusion as a result of nitric oxide (NO) inhibition in endotoxic shock. Cardiac and regional hemodynamic responses to N-methyl-L-arginine (L-NMA), a nonspecific inhibitor of constitutive and inducible nitric oxide synthase (NOS), were assessed in nine conscious dogs subjected to endotoxin.


METHODS
Lipopolysaccharide (LPS) was titrated to a maximum of 200 microg/kg, IV, over 45 minutes. L-NMA was given in a dose of 20 mg/kg, IV. Hemodynamic parameters were recorded for 6 hours following L-NMA administration.


RESULTS
LPS induced significant decreases in mean arterial blood pressure (MAP), cardiac output (CO), first derivative of left ventricular pressure (dP/dt), coronary blood flow, carotid blood flow, mesenteric blood flow, renal blood flow, and a significant hepatic vasodilation. L-NMA fully reversed the effects of LPS on MAP, heart rate, dP/dt, coronary and carotid blood flow, and reversed mesenteric blood flow and hepatic blood flow at 1 and 3 hours, respectively. L-NMA partially overcame the LPS-induced decrease in renal blood flow at 30 minutes and 1 hour. Except for mesenteric and carotid circulation, L-NMA did not change regional vascular resistance.


CONCLUSIONS
It is likely that constitutive NOS is implicated in immediate cardiac, carotid, mesenteric, and renal vascular changes, whereas inducible NOS accounted for delayed responses in hepatic and coronary circulation.
Doursout
M F
MF
Department of Anesthesiology, The University of Texas-Houston Health Science Center, USA.
Kilbourn
R G
RG
Hartley
C J
CJ
Chelly
J E
JE
D000818:Animals; D003331:Coronary Vessels / Q000187:drug effects*; D004195:Disease Models, Animal; D004285:Dogs; D004791:Enzyme Inhibitors / Q000494:pharmacology / Q000627:therapeutic use*; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors; D012039:Regional Blood Flow / Q000187:drug effects; D012772:Shock, Septic / Q000188:drug therapy* / Q000201:enzymology / Q000503:physiopathology; D014655:Vascular Resistance / Q000187:drug effects; D019323:omega-N-Methylarginine / Q000494:pharmacology / Q000627:therapeutic use*
D004791:Enzyme Inhibitors; D019323:omega-N-Methylarginine; D019001:Nitric Oxide Synthase