Endothelium-independent pressor effect of big endothelin-1 and its inhibition by phosphoramidon in rat mesenteric artery.
We asked whether or not the endothelium plays a functional role in the conversion of big endothelin-1 to endothelin-1 in the perfused rat mesenteric artery. In endothelium-denuded preparations, big endothelin-1 produced a much more potent pressor effect than in intact preparations. Phosphoramidon suppressed the big endothelin-1-induced pressor action without affecting the action of endothelin-1, irrespective of the presence or absence of the endothelium. The amounts of immunoreactive-endothelin in the perfusate during perfusion of endothelium-denuded preparations with big endothelin-1 were extremely low compared with those observed in intact preparations and were not significantly suppressed by the metalloproteinase inhibitor, phosphoramidon, in contrast to the case with intact preparations. When synthetic endothelin-1 was perfused in the endothelium-denuded mesentery, the peptide disappeared from the perfusate more rapidly than with intact preparations, suggesting that endothelin-1 generated from big endothelin-1 is effectively trapped by vascular smooth muscle cells in the endothelium-denuded preparation. Our results suggest that the endothelium is not essential for the conversion of big endothelin-1 to endothelin-1, in rat mesenteric artery.
Hisaki
K
K
Department of Pharmacology, Osaka University of Pharmaceutical Sciences, Japan.
Matsumura
Y
Y
Nishiguchi
S
S
Fujita
K
K
Takaoka
M
M
Morimoto
S
S
D000818:Animals; D001794:Blood Pressure / Q000187:drug effects*; D002217:Carbachol / Q000494:pharmacology; D002793:Cholic Acids / Q000494:pharmacology; D002851:Chromatography, High Pressure Liquid; D019332:Endothelin-1; D016232:Endothelins / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D004730:Endothelium, Vascular / Q000502:physiology*; D006020:Glycopeptides / Q000494:pharmacology*; D066298:In Vitro Techniques; D008297:Male; D017538:Mesenteric Artery, Superior / Q000187:drug effects / Q000502:physiology*; D015260:Neprilysin / Q000037:antagonists & inhibitors*; D009638:Norepinephrine / Q000494:pharmacology; D010477:Perfusion; D011498:Protein Precursors / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D011863:Radioimmunoassay; D051381:Rats; D017207:Rats, Sprague-Dawley
D002793:Cholic Acids; D019332:Endothelin-1; D016232:Endothelins; D006020:Glycopeptides; D011498:Protein Precursors; D002217:Carbachol; D015260:Neprilysin; C028213:3-((3-cholamidopropyl)dimethylammonium)-1-propanesulfonate; C008890:phosphoramidon; D009638:Norepinephrine