Changes in regional hemodynamics after nitric oxide inhibition during ovine bacteremia

We studied the action of nitric oxide synthase (NOS) inhibition on changes in regional blood flow during a continuous infusion of live bacteria. Eighteen ewes were chronically instrumented. After a 7-day recovery period, an infusion of 10(6) colony-forming units/min Pseudomonas aeruginosa was begun. At 24 h, cardiac output increased significantly above baseline in all groups (5.9 +/- 0.4 vs. 8.2 +/- 0.6 l . min(-1) . m(-2)), systemic vascular resistance decreased (1,362 +/- 120 vs. 821 +/- 145 dyn . s . cm(-5). m(-2)), and cerebral, cephalic mesenteric, and hindlimb blood flows increased. The animals were then equally and randomly assigned to a bolus of a NOS inhibitor, either 25 mg/kg N(-)(omega)nitro-L-arginine methyl ester (L-NAME) or 20 mg/kg N-omega-monomethyl-L-arginine (L-NMMA), followed by a continuous infusion of 7 mg . kg(-1)min(-1) L-NMMA or saline. After NOS inhibition, cardiac index decreased [5.6 +/- 0.4 (L-NAME) and 5.5 +/- 0.4 l . min(-1) . m(-2) (L-NMMA)] and remained significantly decreased for 12 h. L-NAME decreased carotid and mesenteric blood flows to 64% of the preseptic baseline, and they remained below baseline for 20 h. L-NMMA decreased blood flows only to preseptic baseline values. NOS inhibitors may affect blood flows independently of their hemodynamic effects.