Sevoflurane and bradykinin-induced calcium mobilization in pulmonary arterial valvular endothelial cells in situ: Sevoflurane stimulates plasmalemmal calcium influx into endothelial cells

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 μM) 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 Ca²⁺ stores with ionomycin (0.1 μM). However, the sevoflurane-induced increase in [Ca²⁺]i was eliminated by removal of the extracellular Ca²⁺ and attenuated by NiCl₂ (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 Ca⁺² 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.