Phosphoramidon, a metalloproteinase inhibitor, suppresses the hypertensive effect of big endothelin-1.
Intravenous (i.v.) injection of big endothelin-1 (1-39, 0.05-1.0 nmol/kg) to anaesthetized rats produced a dose-dependent and long-lasting hypertensive effect, the magnitude of which was similar to that evoked by ET-1 (1-21). In animals given phosphoramidon (0.25 mg/kg per min i.v.), a metalloproteinase inhibitor, the hypertensive effect of big endothelin-1 was markedly attenuated. The same dose of phosphoramidon did not influence the endothelin-1-induced hypertensive effect. The possibility that big endothelin-1 is converted to endothelin-1 by a phosphoramidon-sensitive metalloproteinase in vivo warrants further attention.
Matsumura
Y
Y
Department of Pharmacology, Osaka University of Pharmaceutical Sciences, Japan.
Hisaki
K
K
Takaoka
M
M
Morimoto
S
S
D000758:Anesthesia; D000818:Animals; D001794:Blood Pressure / Q000187:drug effects*; D004305:Dose-Response Relationship, Drug; D019332:Endothelin-1; D016232:Endothelins / Q000037:antagonists & inhibitors* / Q000494:pharmacology; D006020:Glycopeptides / Q000494:pharmacology*; D007275:Injections, Intravenous; D008297:Male; D008666:Metalloendopeptidases / Q000037:antagonists & inhibitors*; D011498:Protein Precursors / Q000037:antagonists & inhibitors* / Q000494:pharmacology; D051381:Rats; D011919:Rats, Inbred Strains
D019332:Endothelin-1; D016232:Endothelins; D006020:Glycopeptides; D011498:Protein Precursors; D008666:Metalloendopeptidases; C008890:phosphoramidon