REGULATION OF NOREPINEPHRINE RELEASE BY BETA(2)-ADRENERGIC RECEPTORS DURING HALOTHANE ANESTHESIA

Background: Presynaptic receptors control norepinephrine (NE) release. It has been hypothesized that epinephrine stimulates prejunctional be ta(2)-adrenergic receptors to facilitate NE release from sympathetic n erve endings, and therefore, presynaptic receptors controlling NE rele ase are potential therapeutic targets to limit the adverse effects of excess sympathetic stimulation during anesthesia. We have previously d emonstrated beta(2)-adrenergic receptor-augmented release of NE in the human forearm and have shown that halothane inhibits sympathetic acti vity in vivo by decreasing the NE spillover Irate into plasma. The goa l of the current study was to determine the effect of halothane on bet a(2)-adrenergic receptor-augmented NE release in a canine hind-limb ex perimental model. Methods: Seven female dogs were studied awake and du ring halothane anesthesia (1.0 minimum alveolar concentration). A trac e dosage of [H-3]NE (15 mu Ci over a 1-min period and 0.6 mu Ci/min th ereafter) was infused into the femoral vein. Before and during femoral arterial administration of isoproterenol at two dosages (30 and 80 mg /min), hind-limb blood flow was measured by an ultrasonic flow probe a nd hind-limb NE spillover by an isotope dilutional technique. Results: In awake dogs, isoproterenol significantly increased hind-limb blood now and NE spillover into the hind limb. Halothane had no effect on ba seline or isoproterenol-stimulated hind-limb blood now (a postjunction al beta(2) effect) but significantly inhibited the isoproterenol-induc ed increase in hind-limb NE spillover (a prejunctional beta(2) effect) . Conclusions The isoproterenol-mediated increase in NE release is inh ibited by halothane anesthesia, indicating that halothane inhibits pre junctional beta(2)-adrenergic receptor regulation of NE release.