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 n ormal 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) vasc ular resistance, marginally increased mean arterial pressure (P = 0.07 ), and decreased oxygen delivery (P = 0.01) compared with normal salin e. In contrast, the effect of L-NMMA on mean pulmonary arterial pressu re, central venous pressure, and pulmonary capillary wedge pressure wa s 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 survi val times (P < 0.05). Thus the effect of L-NMMA was similar on the sys temic arterial circulation in endotoxemic dogs compared with normal do gs but was increased in the venous and pulmonary vascular beds after e ndotoxin, suggesting that the induction of NO production was greater i n low-resistance vessels. We were unable to show that nonselective inh ibition of NO production was beneficial in endotoxemic dogs.