ROLE OF NITRIC-OXIDE IN ENDOTOXIN-INDUCED METABOLIC AND VASCULAR DYSREGULATION OF THE CANINE DIAPHRAGM

We assessed the role of nitric oxide (NO) in the regulation of diaphragmatic O-2 uptake (VO(2)di) and phrenic vascular resistance during endotoxemia in anesthetized, mechanically ventilated dogs. Left diaphragmatic vasculature was isolated and briefly pump perfused with arterial blood at a normal flow rate, at a high rate (50% higher than normal), and at a low rate (60 to 70% lower than normal). At each rate, VO(2)di and phrenic perfusion pressure (Pphr) were measured. Escherichia coli endotoxin (100 mg) was infused intravenously over 90 min in several groups of animals, whereas normal saline was infused into the other. Endotoxin infusion increased VO(2)di and reduced Pphr at a given Row rate. These parameters remained unchanged in the saline-infused animals. Infusion of N-G-nitro-L-arginine methyl ester (LNAME 6 x 10(-4) M) into the phrenic artery of the endotoxin group reversed the decline in Pphr with no effect on VO(2)di. LNAME infusion in the saline group increased Pphr at normal and high Row rates only. Single intravenous injections of LNAME increased arterial pressure and reduced cardiac output in endotoxemic animals, whereas only an increase in arterial pressure was observed in saline-infused animals. Serum arterial and phrenic venous NO concentrations measured in separate groups of animals increased significantly after endotoxin infusion, whereas saline infusion had no effect on these parameters. These results indicate that enhanced NO release plays a significant role in endotoxin-induced phrenic and systemic vasodilation. However, the increase in VO(2)di in the endotoxin group does not seem to be mediated by NO release.