Volatile anesthetics affect calcium mobilization in bovine endothelial cells

Background: The site where volatile anesthetics inhibit endothelium-dependent, nitric oxide-mediated vasodilation is unclear. To determine whether anesthetics could limit endothelium-dependent nitric oxide production by inhibiting receptor-mediated increases in cytosolic Ca2+, experiments were performed to see if the inhalational anesthetics halothane, isoflurane, and enflurane affect intracellular Ca2+ ([Ca2+](i)) transients induced by the agonists bradykinin and adenosine triphosphate in cultured bovine aortic endothelial cells. Methods: Bovine aortic endothelial cells, which had been loaded with the fluorescent Ca2+ indicator Fura-2, were added to medium preequilibrated with volatile anesthetic (1.25% and 2.5% for isoflurane, 1.755 and 3.5% for enflurane, and 0.75% and 1.5% for halothane). In Ca2+-containing medium, intracellular Ca2+ transients were elicited in response to bradykinin (10 nM and 1 mu M) or adenosine triphosphate (1 mu M and 100 mu M). Results: Both bradykinin and adenosine triphosphate triggered a rapid rise to peak [Ca2+](i) followed by a gradual decline to a plateau above the resting level. Although basal [Ca2+](i) was unaltered by the anesthetics, both halothane and enflurane, in a dose-dependent manner, depressed the peak and plateau of the [Ca2+](i) transient elicited by 10 nM bradykinin, whereas isoflurane had no effect. When [Ca2+](i) transients were elicited by 1 mu M bradykinin, halothane (1% and 5%) did not alter peak and plateau levels. Halothane and enflurane also decreased [Ca2+](i) transients evoked by 1 mu M and 100 mu M adenosine triphosphate, whereas isoflurane also had no effect in this setting. Conclusions: Halothane and enflurane, but not isoflurane, inhibit bradykinin- and adenosine triphosphate-stimulated Ca2+ transients in endothelial cells. Limitations of Ca2+ availability to activate constitutive endothelial nitric oxide synthase could allow for part, but not all, of the inhibition of endothelium-dependent nitric oxide-mediated vasodilation by inhalational anesthetics.