INTRARENAL CONVERSION OF BIG ENDOTHELIN-1 TO ENDOTHELIN-1 IN THE RAT

Intravenous (i.v.) or intrarenal arterial (i.r.a.) injection of big en dothelin-l (big ET-1) (1.6 nmol/kg) in anesthetized rats produced a si gnificant increase in mean arterial pressure (MAP), a decrease in rena l blood flow (RBF) and an increase in renal vascular resistance (RVR). Although the presser responses to big ET-1 of i.v. and i.r.a. injecti on were not significantly different, i.r.a. injection of big ET-I caus ed a significantly greater reduction in RBF than that seen with i.v. i njection of big ET-1. The effects of i.r.a. injection of the peptide a n MAP and RBF were markedly suppressed by phosphoramidon. Big ET-1 cau sed dose-dependent presser effects in isolated perfused rat kidney and these presser effects were significantly suppressed by phosphoramidon . Thus, renal vasculature possesses a phosphoramidon-sensitive endothe lin converting enzyme, which may play an important role for the renal hemodynamic regulation.