Nitric oxide synthase inhibition during experimental sepsis improves renal excretory function in the presence of chronically increased atrial natriuretic peptide.

OBJECTIVE

To test whether renal excretory function decreases after nitric oxide synthase inhibition during experimental hyperdynamic sepsis.

DESIGN

Prospective, randomized, controlled animal trial.

SETTING

Research laboratory at a large university medical center.

SUBJECTS

Chronically instrumented Merino breed ewes (n = 18).

INTERVENTIONS

Continuous 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, N omega-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 RESULTS

The sheep developed a hyperdynamic cardiovascular response characterized by a decrease in systemic vascular resistance index (p < .05), and an increased cardiac index (p < .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 N omega-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 < .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 N omega-nitro-L-arginine methyl ester administration.

CONCLUSIONS

In 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, N omega-nitro-L-arginine methyl ester, reverses the vasodilatory state, thereby improving fluid balance and glomerular filtration.