Role of prostaglandins and endothelium-derived relaxing factor on the renal response to acetylcholine

Abstract

Acetylcholine (ACh) stimulates the endothelial release of prostacyclin and endothelium-derived relaxing factor (EDRF). However, the relative participation of these substances in mediating the renal effects of ACh remains undefined. To elucidate this issue, we studied the modifications of renal responses to intra-renal ACh infusion (25 ng.kg-1.min-1) produced by blocking the synthesis of EDRF and/or prostaglandins (PG) in anesthetized dogs. ACh induced a significant increase in renal blood flow (RBF) (34%), urine volume (UV) (450%), and urinary sodium excretion (UNaV)(259%), which remained unaltered after blocking the synthesis of EDRF [NG-monomethyl-L-arginine (LNMMA), 50 micrograms.kg-1.min-1 intrarenal] or PG (meclofenamate, 5 mg/kg iv). However, the simultaneous administration of meclofenamate and LNMMA prevented the ACh-induced increase in RBF and UV but not in UNaV. The concomitant infusion of L-arginine but not D-arginine prevented these blocking effects of LNMMA. It was concluded that the ACh-induced increases in RBF and UV, but not UNaV, are mediated by both PG and EDRF. The hemodynamic and diuretic effect of either one of these mediators can be fully compensated during the blockade of the other.