HALOTHANE INHIBITS BRADYKININ-STIMULATED PROSTACYCLIN PRODUCTION IN ENDOTHELIAL-CELLS

Background: Halothane and isoflurane alter signal transduction and fun ction in several cell types. Vascular responses to these anesthetics m ay be attributable to agent-specific effects on vasoactive mediator pr oduction. This study investigated the effects of halothane and isoflur ane on basal and agonist-stimulated prostacyclin production by endothe lial cells. Methods: Prostacyclin production by cultured bovine aortic endothelial cells was monitored by radioimmunoassay of 6-keto-prostag landin F-1 alpha, the stable breakdown product of prostacyclin. Result s: Neither halothane nor isoflurane (0.3-1 mM) altered prostacyclin pr oduction. Bradykinin (1 mu M), adenosine triphosphate (ATP) (10 mu M), and melittin (1 mu g.ml(-1)) stimulated prostacyclin production. Isof lurane had no effect on responses to bradykinin, ATP, or melittin. Hal othane inhibited the response to bradykinin but not the response to AT P or melittin. Pretreatment with pertussis toxin (100 ng.ml(-1)), to i nhibit the function of the guanosine triphosphate-binding protein G(al pha 1), did not alter the response to bradykinin in the presence or ab sence of halothane. Pretreatment with phorbol 12-myristate 13-acetate (100 nM), to stimulate protein kinase C activity, did not alter bradyk inin-stimulated prostacyclin production and prevented the inhibition o f the response to bradykinin by halothane. Conclusions: Isoflurane had no effect on the increase in prostacyclin production stimulated by br adykinin. Halothane inhibited the bradykinin-stimulated prostacyclin p roduction but not that stimulated by ATP or melittin. These results su ggest 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.