Halothane inhibits bradykinin-stimulated prostacyclin production in endothelial cells.
BACKGROUND
Halothane and isoflurane alter signal transduction and function in several cell types. Vascular responses to these anesthetics may be attributable to agent-specific effects on vasoactive mediator production. This study investigated the effects of halothane and isoflurane on basal and agonist-stimulated prostacyclin production by endothelial cells.


METHODS
Prostacyclin production by cultured bovine aortic endothelial cells was monitored by radioimmunoassay of 6-keto-prostaglandin F1 alpha, the stable breakdown product of prostacyclin.


RESULTS
Neither halothane nor isoflurane (0.3-1 mM), altered prostacyclin production. Bradykinin (1 microM), adenosine triphosphate (ATP) (10 microM), and melittin (1 microgram.ml-1) stimulated prostacyclin production. Isoflurane had no effect on responses to bradykinin, ATP, or melittin. Halothane inhibited the response to bradykinin but not the response to ATP or melittin. Pretreatment with pertussis toxin (100 ng.ml-1), to inhibit the function of the guanosine triphosphate-binding protein G alpha i, did not alter the response to bradykinin in the presence or absence of halothane. Pretreatment with phorbol 12-myristate 13-acetate (100 nM), to stimulate protein kinase C activity, did not alter bradykinin-stimulated prostacyclin production and prevented the inhibition of the response to bradykinin by halothane.


CONCLUSIONS
Isoflurane had no effect on the increase in prostacyclin production stimulated by bradykinin. Halothane inhibited the bradykinin-stimulated prostacyclin production but not that stimulated by ATP or melittin. These results suggest that the halothane-mediated inhibition of bradykinin-stimulated prostacyclin production does not involve a pertussis toxin-sensitive G-protein and may result from an interaction of halothane at some other step in the signal transduction pathway, including the inhibition of protein kinase C.
Loeb
A L
AL
Department of Anesthesia, University of Pennsylvania, Philadelphia 19104-4283.
O'Brien
D K
DK
Longnecker
D E
DE
D000255:Adenosine Triphosphate / Q000494:pharmacology; D000818:Animals; D001920:Bradykinin / Q000494:pharmacology*; D002417:Cattle; D002478:Cells, Cultured; D004347:Drug Interactions; D004730:Endothelium, Vascular / Q000166:cytology* / Q000378:metabolism*; D011464:Epoprostenol / Q000378:metabolism*; D006221:Halothane / Q000494:pharmacology*; D007530:Isoflurane / Q000494:pharmacology; D008555:Melitten / Q000494:pharmacology; D037342:Pertussis Toxin; D011863:Radioimmunoassay; D010566:Virulence Factors, Bordetella / Q000494:pharmacology
D010566:Virulence Factors, Bordetella; D008555:Melitten; D000255:Adenosine Triphosphate; D007530:Isoflurane; D011464:Epoprostenol; D037342:Pertussis Toxin; D001920:Bradykinin; D006221:Halothane