EXOGENOUS CGMP PREVENTS DECREASE IN DIURESIS AND NATRIURESIS INDUCED BY INHIBITION OF NO SYNTHESIS

We previously demonstrated that the intravenous infusion of the specific inhibitor of nitric oxide (NO) synthesis, N(G)-nitro-L-arginine methyl ester (L-NAME), over a period of 60 min elevates mean arterial pressure (MAP) and reduces renal hemodynamics and excretory function. The objective of the present study was to determine the ability of a guanosine 3',5'-cyclic monophosphate (cGMP) analogue, 8-bromo-cGMP (8-BrcGMP), in preventing the increase in MAP and the reductions in renal plasma flow (RPF), glomerular filtration rate (GFR), urine flow (UV), and sodium excretion rate (U(Na)V) induced by intravenous infusion Of L-NAME in rats. As expected, the infusion of L-NAME (50 mug . kg-1. min-1) increased (P < 0.05) MAP and reduced (P < 0.05) RPF, GFR, UV, and U(Na)V. The administration of 8-BrcGMP (100 mug . kg-1 . min-1) and L-NAME resulted in no change in MAP, RPF, and GFR. However, decreased (P < 0.05) UV and U(Na)V were still observed. When 8-BrcGMP (200 mug . kg-1 . min-1) and L-NAME were infused together, no significant changes in MAP or in renal function were observed. To prove the specificity of the 8-BrcGMP preventive effects, dibutyryl cAMP (200 mug . kg-1. min-1) and L-NAME (50 mug . kg-1 . min-1) were infused together. Under these conditions, MAP, RPF, GFR, UV, and U(Na)V were modified in a manner similar to that observed during the infusion of L-NAME. The administration of 8-BrcGMP (200 mug . kg-1 . min-1) for 60 min did not modify any of the parameters measured, thus ruling out the possibility of a pharmacological antagonism in the preventive effect of 8-BrcGMP on L-NAME actions. However, the administration of 8-BrcGMP (500 mug . kg-1 . min-1) significantly reduced MAP, UV, and U(Na)V and increased RPF. The reduction in renal excretory parameters was probably a consequence of the drop in MAP observed during this infusion. Therefore the present results suggest that the effects of L-NAME on MAP, renal hemodynamics, and renal excretory function are mediated by a decreased availability of cGMP, because the exogenous administration of 8-Br-cGMP prevents those effects.