抄録
Sivelestat is a neutrophil elastase inhibitor and the effects of sivelestat on the contractile regulation of vascular smooth muscle(VSM) have not been reported. This study was designed to determine whether sivelestat affects the contractility of porcine coronary arteries, and if so, to elucidate the underlying mechanism(s) and particularly those involving the Ca2＋ sensitization of VSM.
Sivelestat induced the concentration-dependent(3×10－5－3×10－4 M) vasorelaxation of porcine coronary arteries, with or without endothelium, when precontracted with U46619(G protein-coupled receptor agonist; 100 nM). Simultaneous measurements of tension and [Ca2＋]i demonstrated that sivelestat shifted the [Ca2＋]i-tension curve to the right and downward during stimulation with 118 mM K＋ and 100 nM U46619. In β-escin-permeabilized arterial strips, sivelestat abolished contractions induced by GTP plus U46619 at a constant [Ca2＋]i, whereas it had no effect on Ca2＋-induced contractions. These findings suggested that sivelestat induced vasorelaxation via selective inhibition of the Ca2＋ sensitization induced by U46619, without affecting Ca2＋-induced contractions.
In conclusion, sivelestat relaxes porcine coronary artery smooth muscle via a selective inhibition of Ca2＋ sensitization induced by a G protein-coupled receptor agonist, without affecting Ca2＋-induced contractions.
