EFFECTS OF VERAPAMIL ON THE RENAL ACTIONS INDUCED BY NITRIC-OXIDE ANDPROSTAGLANDIN SYNTHESIS INHIBITION

This study was designed to determine the effects of a calcium antagoni st (verapamil) on the renal actions induced by nitric oxide synthesis inhibition, with and without simultaneous prostaglandin synthesis inhi bition. The renal effects of verapamil (2 mu g/kg/min) were examined i n anesthetized dogs before and after an increase of extracellular volu me and during the reduction of nitric oxide synthesis (1 mu g/kg/min N -G-nitro-L-arginine methyl ester [L-NAME]), with and without the admin istration of a cyclooxygenase inhibitor (5 mu g/kg/min meclofenamate). Nitric oxide synthesis inhibition produced an increase in proximal so dium reabsorption (lithium clearance technique) and a decrease in the excretory response to volume expansion that was prevented by the admin istration of verapamil. The administration of a cyclooxygenase inhibit or, during nitric oxide synthesis inhibition, elicited an increase in arterial pressure, an important renal vasoconstriction, and reduced th e renal excretory response to volume expansion. The antinatriuretic ef fect produced by the simultaneous reduction of nitric oxide and prosta glandin synthesis, before and after the volume expansion, was abolishe d with the verapamil infusion. However, the increase of arterial press ure and renal vasoconstriction were only partly affected by verapamil. We found that the antinatriuretic effect secondary to the reduction o f nitric oxide synthesis, during an increase in extracellular volume, is prevented by the administration of verapamil. Additionally, the adm inistration of verapamil completely prevents the antinatriuretic, but not the vasoconstrictor, effects induced by the administration of a cy clooxygenase inhibitor when nitric oxide is slightly reduced.