HALOTHANE MYOCARDIAL DEPRESSION - INTERACTIONS WITH THE ADENYLATE-CYCLASE SYSTEM

The involvement of the adenylate cyclase system in myocardial depressi on by halothane was investigated in an isolated, electrically stimulat ed, rat left atrial preparation. The twitch tension dose-response curv e to the muscarinic agent, carbachol, was unaltered by 0.27 mM (0.8%) halothane. Pertussis toxin irreversibly blocks the inhibition of adeny late cyclase by muscarinic agonists. Atria from animals pretreated wit h pertussis toxin were insensitive to the negative inotropic effect of carbachol, but the depression in twitch tension by halothane was unal tered. Halothane shifted the dose-response curve to isoproterenol down ward and to the right. However, the depression in twitch tension by 0. 27 mM halothane was similar in preparations incubated with the nonhydr olyzable cAMP analogue, dibutyryl-cAMP, compared to control atria stim ulated with isoproterenol. We conclude that halothane attenuates the r esponse to beta-adrenergic stimulation in myocardial tissue, and alter ations in adenylate cyclase activity do not contribute significantly t o this process.