Effects of N-methyl-L-arginine on cardiac and regional blood flow in a dogendotoxin shock model

Purpose: Indirect evidence suggests a decrease in organ perfusion as a resu lt of nitric oxide (NO) inhibition in endotoxic shock. Cardiac and regional hemodynamic responses to N-methyl-L-arginine (L-NMA), a nonspecific inhibi tor of constitutive and inducible nitric oxide synthase (NOS), were assesse d in nine conscious dogs subjected to endotoxin. Materials and Methods: Lipopolysaccharide (LPS) was titrated to a maximum o f 200 mu g/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 admini stration. 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, ren al 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 f low, and reversed mesenteric blood flow and hepatic blood how at 1 and 3 ho urs, respectively. L-PIMA partially overcame the LPS-induced decrease in re nal 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. C opyright (C) 2000 by W.B. Saunders Company.