Intrarenal conversion of big endothelin-1 to endothelin-1 in the rat

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