Differences in potency of big endothelin-1-induced pressor action in rat isolated perfused mesenteric artery, hindquarter and lung.
We compared the pressor response to endothelin-1 (ET-1) with that of big endothelin-1 (big ET-1) in mesenteric arteries, hindquarters and lungs of rats. In these three preparations, both peptides caused a concentration-dependent increase in the perfusion pressure. The ratio of big ET-1 concentration to ET-1 concentration needed for causing the same pressor action is different between organs; i.e., a mesentery >> a hindquarter > or = a lung. Exposure to phosphoramidon, a metalloproteinase inhibitor, significantly suppressed the pressor response to big ET-1, in a similar fashion. This suppression is likely to be due to the inhibition of phosphoramidon-sensitive endothelin converting enzyme, since the inhibitor does not suppress an action of ET-1. Apparently there is a difference in potency for phosphoramidon-sensitive vasoconstriction of big ET-1 between organs and presumably regional differences in the functional phosphoramidon-sensitive conversion of big ET-1 in vasculatures.
Hisaki
K
K
Department of Pharmacology, Osaka University of Pharmaceutical Sciences, Japan.
Matsumura
Y
Y
Fujita
K
K
Maekawa
H
H
Takaoka
M
M
Morimoto
S
S
D000818:Animals; D016282:Aspartic Acid Endopeptidases / Q000037:antagonists & inhibitors / Q000378:metabolism; D001794:Blood Pressure / Q000187:drug effects*; D004305:Dose-Response Relationship, Drug; D019332:Endothelin-1; D000072396:Endothelin-Converting Enzymes; D016232:Endothelins / Q000494:pharmacology*; D006020:Glycopeptides / Q000494:pharmacology; D006614:Hindlimb / Q000098:blood supply*; D008168:Lung / Q000098:blood supply*; D008297:Male; D017538:Mesenteric Artery, Superior / Q000187:drug effects*; D008666:Metalloendopeptidases; D010477:Perfusion; D011498:Protein Precursors / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D014661:Vasoconstriction / Q000187:drug effects
D019332:Endothelin-1; D016232:Endothelins; D006020:Glycopeptides; D011498:Protein Precursors; D016282:Aspartic Acid Endopeptidases; D008666:Metalloendopeptidases; D000072396:Endothelin-Converting Enzymes; C008890:phosphoramidon