ObjectiveTo test whether renal excretory function decreases after nitric oxide synthase inhibition during experimental hyperdynamic sepsis.DesignProspective, randomized, controlled animal trial.SettingResearch laboratory at a large university medical center.SubjectsChronically instrumented Merino breed ewes (n equals 18).InterventionsContinuous infusion of Escherichia coli endotoxin (10 ng/kg/min) for the experimental period of 32 hrs. One group received a bolus of the nitric oxide synthase inhibitor, Nomega-nitro-L-arginine methyl ester (25 mg/kg), after 24 hrs, and the remaining sheep were given the carrier, sodium chloride 0.9%.Measurements and Main ResultsThe sheep developed a hyperdynamic cardiovascular response characterized by a decrease in systemic vascular resistance index (p less than .05), and an increased cardiac index (p less than .05) by 24 hrs. The sheep retained fluid, with creatinine clearance decreasing in the presence of chronically increased atrial natriuretic peptide. After the administration of Nomega-nitro-L-arginine methyl ester, systemic vascular resistance index and cardiac index returned to baseline values, fluid balance normalized, and glomerular filtration rate increased (p less than .05), while the control animals continued to retain fluid and their creatinine clearance continued to decrease. The concentrations of atrial natriuretic peptide did not differ significantly between groups after Nomega-nitro-L-arginine methyl ester administration.ConclusionsIn this ovine model of experimental hyperdynamic sepsis, renal excretory function decreases in the presence of chronically increased concentrations of atrial natriuretic peptide. Administration of the nitric oxide synthase inhibitor, Nomega-nitro-L-arginine methyl ester, reverses the vasodilatory state, thereby improving fluid balance and glomerular filtration.(Crit Care Med 1996; 24:131-136)