title: Sivelestat relaxes vascular smooth muscle contraction in human gastric arteries.
abstract: 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. It is important to determine how sivelestat affects hemodynamics and the regulatory mechanisms of vascular smooth muscle (VSM). We recently found that sivelestat relaxes porcine coronary artery VSM via selective inhibition of Ca(2+) sensitization induced by a receptor agonist without affecting the normal Ca(2+)-induced contraction. Although sivelestat relaxes porcine artery, its effects on human artery are unknown; therefore, the purpose of the present study was to assess the effects of sivelestat on human artery. In the present study, sivelestat induced concentration-dependent (1 × 10(-6) to 3 × 10(-4) M) vasorelaxation in U46619 (1 nM) and sphingosylphosphorylcholine (SPC) (30 mM)-precontracted human gastric artery with or without endothelium, but sivelestat did not induce vasorelaxation in conditions of high K(+) (40 mM) depolarization. Sivelestat inhibited VSM contraction by an agonist and SPC, and it did not affect Ca(2+)-induced normal physiologic contraction.
authors.affiliation: Department of Anesthesiology and Critical Care Medicine, Saga Medical School, 5-1-1 Nabeshima, Saga, 849-8501, Japan. amemohi@cc.saga-u.ac.jp
authors.forename: Hiroko
authors.initials: H
authors.lastname: Amemori
authors.forename: Yoshinori
authors.initials: Y
authors.lastname: Maeda
authors.forename: Arisu
authors.initials: A
authors.lastname: Torikai
authors.forename: Mikio
authors.initials: M
authors.lastname: Nakashima
mesh_terms: D000368:Aged; D001158:Arteries / Q000187:drug effects* / Q000502:physiology; D004305:Dose-Response Relationship, Drug; D004730:Endothelium, Vascular / Q000187:drug effects / Q000502:physiology; D005998:Glycine / Q000031:analogs & derivatives* / Q000494:pharmacology; D006439:Hemodynamics / Q000187:drug effects; D006801:Humans; D066298:In Vitro Techniques; D008875:Middle Aged; D009119:Muscle Contraction / Q000187:drug effects*; D009129:Muscle Tonus / Q000187:drug effects; D009131:Muscle, Smooth, Vascular / Q000187:drug effects* / Q000502:physiology; D013270:Stomach / Q000098:blood supply* / Q000187:drug effects; D013449:Sulfonamides / Q000494:pharmacology*; D014661:Vasoconstriction / Q000187:drug effects; D014664:Vasodilation / Q000187:drug effects; D014665:Vasodilator Agents / Q000494:pharmacology*
chemical_list: D013449:Sulfonamides; D014665:Vasodilator Agents; C069195:sivelestat; D005998:Glycine