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 Ca(2+)-containing medium, intracellular Ca2+ transients were elicited in response to bradykinin (10 nM and 1 microM) or adenosine triphosphate (1 microM and 100 microM).


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 microM bradykinin, halothane (1% and 5%) did not alter peak and plateau levels. Halothane and enflurane also decreased [Ca2+]i transients evoked by 1 microM and 100 microM 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.
Pajewski
T N
TN
Department of Anesthesiology, University of Virginia Health Sciences Center, Charlottesville 22906-0010, USA. tnp9s@virginia.edu
Miao
N
N
Lynch
C
C
Johns
R A
RA
D000255:Adenosine Triphosphate / Q000494:pharmacology; D018685:Anesthetics, Inhalation / Q000494:pharmacology*; D000818:Animals; D001920:Bradykinin / Q000494:pharmacology; D002118:Calcium / Q000378:metabolism*; D002417:Cattle; D002478:Cells, Cultured; D003593:Cytoplasm / Q000502:physiology; D004730:Endothelium, Vascular / Q000187:drug effects* / Q000378:metabolism; D004737:Enflurane / Q000494:pharmacology*; D006221:Halothane / Q000494:pharmacology*; D007530:Isoflurane / Q000494:pharmacology*
D018685:Anesthetics, Inhalation; D000255:Adenosine Triphosphate; D004737:Enflurane; D007530:Isoflurane; D001920:Bradykinin; D002118:Calcium; D006221:Halothane