title: Sevoflurane and bradykinin-induced calcium mobilization in pulmonary arterial valvular endothelial cells in situ: sevoflurane stimulates plasmalemmal calcium influx into endothelial cells.
abstract: Kinins locally synthesized in the cardiovascular tissue are believed to contribute to the regulation of cardiovascular homeostasis by stimulating the endothelial cells to release nitric oxide, prostacyclin, or a hyperpolarizing factor via autocrine-paracrine mechanisms. This study was designed to investigate the action of sevoflurane on bradykinin-induced Ca2+ mobilization in endothelial cells in situ. Utilizing fura-2-loaded rat pulmonary arterial valve leaflets, the effects of sevoflurane were examined on bradykinin-induced increases in intracellular Ca2+ concentration ([Ca2+]i) in endothelial cells in situ. In the presence of extracellular Ca2+ (1.5 mM), bradykinin (3-30 microM) produced an initial phasic and a subsequent tonic increase in [Ca2+]i in a concentration-dependent manner. However, it produced only the phasic increase in [Ca2+]i in the absence of extracellular Ca2+. Sevoflurane (5%, 0.67 mM) inhibited both the phasic and tonic responses to bradykinin. In these experiments, sevoflurane (3-5%) generated sustained increases (approximately 20-40% of the bradykinin-induced maximal increase in [Ca2+]i) in the resting [Ca2+]i level. Sevoflurane still increased [Ca2+]i after depletion of the intracellular Ca stores with ionomycin (0.1 microM ). However, the sevoflurane-induced increase in [Ca2+]i was eliminated by removal of the extracellular Ca and attenuated by NiCl (1-3 mM). In conclusion, in the pulmonary arterial valvular endothelial cells, sevoflurane inhibits both bradykinin-induced Ca2+ release from the intracellular stores and bradykinin-induced plasmalemmal Ca2+ influx. In addition, sevoflurane appears to stimulate the plasmalemmal Ca2+ influx and thereby increase the endothelial [Ca2+]i level. Sevoflurane might influence the pulmonary vascular tone through its direct action on the pulmonary arterial valvular endothelial cells.
authors.affiliation: Department of Disaster and Emergency Medicine, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan.
authors.forename: Tomoo
authors.initials: T
authors.lastname: Kanna
authors.forename: Takashi
authors.initials: T
authors.lastname: Akata
authors.forename: Kaoru
authors.initials: K
authors.lastname: Izumi
authors.forename: Mikio
authors.initials: M
authors.lastname: Nakashima
authors.forename: Yoshikazu
authors.initials: Y
authors.lastname: Yonemitsu
authors.forename: Makoto
authors.initials: M
authors.lastname: Hashizume
authors.forename: Shosuke
authors.initials: S
authors.lastname: Takahashi
mesh_terms: D018685:Anesthetics, Inhalation / Q000494:pharmacology*; D000818:Animals; D001920:Bradykinin / Q000494:pharmacology*; D002118:Calcium / Q000378:metabolism*; D004357:Drug Synergism; D004730:Endothelium, Vascular / Q000187:drug effects*; D005470:Fluorometry; D008297:Male; D008738:Methyl Ethers / Q000494:pharmacology*; D011664:Pulmonary Valve / Q000187:drug effects / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D000077149:Sevoflurane
chemical_list: D018685:Anesthetics, Inhalation; D008738:Methyl Ethers; D000077149:Sevoflurane; D001920:Bradykinin; D002118:Calcium