Halothane myocardial depression: interactions with the adenylate cyclase system

The involvement of the adenylate cyclase system in myocardial depression by halothane was investigated in an isolated, electrically stimulated, rat left atrial preparation. The twitch tension dose-response curve to the muscarinic agent, carbachol, was unaltered by 0.27 mM (0.8%) halothane. Pertussis toxin irreversibly blocks the inhibition of adenylate cyclase by muscarinic agonists. Atria from animals pretreated with pertussis toxin were insensitive to the negative inotropic effect of carbachol, but the depression in twitch tension by halothane was unaltered. Halothane shifted the dose-response curve to isoproterenol downward and to the right. However, the depression in twitch tension by 0.27 mM halothane was similar in preparations incubated with the nonhydrolyzable cAMP analogue, dibutyryl-cAMP, compared to control atria stimulated with isoproterenol. We conclude that halothane attenuates the response to beta-adrenergic stimulation in myocardial tissue, and alterations in adenylate cyclase activity do not contribute significantly to this process.