Sivelestat relaxes porcine coronary artery via inhibition of Ca2+ sensitization induced by a receptor agonist.
Sivelestat sodium hydrate (sivelestat) is a novel synthetic drug and specific inhibitor of neutrophil elastase that has been approved in Japan as a treatment for acute lung injury associated with systemic inflammatory response syndrome. There are no reports on the effects of sivelestat on the contractile regulation of vascular smooth muscle. The purpose of the present study was to assess the effects of sivelestat on porcine coronary artery. Sivelestat induced concentration-dependent (3 x 10 to 3 x 10 M) vasorelaxation in U46619 (100 nM)-precontracted porcine coronary artery with or without endothelium. Simultaneous measurements of tension and the cytosolic Ca concentration ([Ca]i) revealed that sivelestat shifted the [Ca]i-tension curve to the right and downward during stimulation with 118 mM K and 100 nM U46619. In beta-escin-permeabilized arterial strips, sivelestat abolished GTP plus U46619-induced contractions at constant [Ca]i, whereas it had no effect on Ca-induced contractions. Thus, sivelestat relaxes porcine coronary artery smooth muscle via the selective inhibition of Ca sensitization induced by a receptor agonist, without affecting Ca-induced contraction.
Maeda
Yoshinori
Y
Department of Anesthesiology and Critical Care Medicine, Saga Medical School, Saga, Japan.
Mitsumizo
Shinji
S
Guo
Fengling
F
Kishi
Hiroko
H
Matsuo
Sayaka
S
Kobayashi
Sei
S
Nakashima
Mikio
M
D019796:15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5,13-dienoic Acid / Q000494:pharmacology*; D000818:Animals; D002118:Calcium / Q000378:metabolism*; D003331:Coronary Vessels / Q000187:drug effects* / Q000502:physiology; D004730:Endothelium, Vascular / Q000187:drug effects / Q000502:physiology; D005998:Glycine / Q000031:analogs & derivatives* / Q000494:pharmacology; D066298:In Vitro Techniques; D007537:Isometric Contraction / Q000187:drug effects; D009126:Muscle Relaxation / Q000187:drug effects; D009131:Muscle, Smooth, Vascular / Q000187:drug effects* / Q000502:physiology; D013449:Sulfonamides / Q000494:pharmacology*; D013552:Swine; D014662:Vasoconstrictor Agents / Q000494:pharmacology*; D014665:Vasodilator Agents / Q000494:pharmacology*
D013449:Sulfonamides; D014662:Vasoconstrictor Agents; D014665:Vasodilator Agents; D019796:15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5,13-dienoic Acid; C069195:sivelestat; D002118:Calcium; D005998:Glycine