Effects of acute nitric oxide inhibition on rat glomerular microcirculation

Abstract

Endothelium-derived relaxing factor (EDRF), recently identified as nitric oxide (NO), has been shown to be released by glomerular endothelial cells and might influence the glomerular microcirculation. To examine this hypothesis, we studied in rats the renal effect of acute administration of NG-monomethyl-L-arginine (L-NMMA), a specific inhibitor of NO synthesis. Adult male Munich-Wistar rats were studied before and after intravenous administration of either pure saline or a bolus injection of L-NMMA (20 mg) followed by a continuous infusion of the inhibitor (0.4 mg/min). Although saline alone had no effect on systemic or glomerular hemodynamics, L-NMMA promoted marked systemic hypertension, glomerular arteriolar vasoconstriction, and glomerular hypoperfusion. Since efferent resistance was disproportionately increased, glomerular hydraulic pressure was also markedly elevated. The glomerular ultrafiltration coefficient (Kf) fell to 42% of control. Single-nephron glomerular filtration rate was unaffected. Striking polyuria was also observed. These findings suggest that EDRF exerts a basal relaxing effect on the glomerular microcirculation.