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

Purpose: 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.

Materials And 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.