Big endothelin-3-induced hypertension and its inhibition by phosphoramidon in anaesthetized rats.
Intravenous injection of big endothelin-3 (big ET-3, 1-41 amide) at 3 nmol/kg to ganglion-blocked anaesthetized rats produced a long-lasting hypertensive action, but the action was less potent than that seen with the same dose of ET-3-(1-21). The pressor effect induced by big ET-3 was markedly attenuated by pretreatment with phosphoramidon, 5 mg/kg i.v., a dose which had no effect on the hypertensive action induced by ET-3. These results strongly suggest that big ET-3 is converted to mature ET-3 by a phosphoramidon-sensitive metalloproteinase in vivo, in a manner similar to the conversion of big ET-1 to ET-1.
Matsumura
Y
Y
Department of Pharmacology, Osaka University of Pharmaceutical Sciences, Japan.
Fujita
K
K
Takaoka
M
M
Morimoto
S
S
D000758:Anesthesia; D000818:Animals; D001794:Blood Pressure / Q000187:drug effects*; D019332:Endothelin-1; D016232:Endothelins / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D005730:Ganglionic Blockers; D006020:Glycopeptides / Q000494:pharmacology*; D008297:Male; D011498:Protein Precursors / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D013820:Thermolysin / Q000037:antagonists & inhibitors*
D019332:Endothelin-1; D016232:Endothelins; D005730:Ganglionic Blockers; D006020:Glycopeptides; D011498:Protein Precursors; D013820:Thermolysin; C008890:phosphoramidon