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.
Fujita
K
K
Department of Pharmacology, Osaka University of Pharmaceutical Sciences, Japan.
Matsumura
Y
Y
Kita
S
S
Hisaki
K
K
Takaoka
M
M
Morimoto
S
S
D000818:Animals; D001794:Blood Pressure / Q000187:drug effects*; D019332:Endothelin-1; D016232:Endothelins / Q000008:administration & dosage / Q000378:metabolism* / Q000494:pharmacology; D006020:Glycopeptides / Q000494:pharmacology; D066298:In Vitro Techniques; D007275:Injections, Intravenous; D007668:Kidney / Q000098:blood supply* / Q000187:drug effects / Q000378:metabolism; D008297:Male; D011498:Protein Precursors / Q000008:administration & dosage / Q000378:metabolism* / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D012079:Renal Circulation / Q000187:drug effects*; D014655:Vascular Resistance / Q000187:drug effects; D014661:Vasoconstriction / Q000187:drug effects
D019332:Endothelin-1; D016232:Endothelins; D006020:Glycopeptides; D011498:Protein Precursors; C008890:phosphoramidon