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 beta 2-adrenergic receptors to facilitate NE release from sympathetic nerve endings, and therefore, presynaptic receptors controlling NE release are potential therapeutic targets to limit the adverse effects of excess sympathetic stimulation during anesthesia. We have previously demonstrated beta 2-adrenergic receptor-augmented release of NE in the human forearm and have shown that halothane inhibits sympathetic activity in vivo by decreasing the NE spillover rate into plasma. The goal of the current study was to determine the effect of halothane on beta 2-adrenergic receptor-augmented NE release in a canine hind-limb experimental model.


METHODS
Seven female dogs were studied awake and during halothane anesthesia (1.0 minimum alveolar concentration). A trace dosage of [3H]NE (15 microCi over a 1-min period and 0.6 microCi/min thereafter) 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 and hind-limb NE spillover by an isotope dilutional technique.


RESULTS
In awake dogs, isoproterenol significantly increased hind-limb blood flow and NE spillover into the hind limb. Halothane had no effect on baseline or isoproterenol-stimulated hind-limb blood flow (a postjunctional beta 2 effect) but significantly inhibited the isoproterenol-induced increase in hind-limb NE spillover (a prejunctional beta 2 effect).


CONCLUSIONS
The isoproterenol-mediated increase in NE release is inhibited by halothane anesthesia, indicating that halothane inhibits prejunctional beta 2-adrenergic receptor regulation of NE release.
Deegan
R
R
Department of Pharmacology, Vanderbilt University, Nashville, Tennessee, USA.
He
H B
HB
Krivoruk
Y
Y
Wood
A J
AJ
Wood
M
M
D000758:Anesthesia; D000818:Animals; D004285:Dogs; D005260:Female; D006221:Halothane / Q000494:pharmacology*; D007545:Isoproterenol / Q000494:pharmacology; D009638:Norepinephrine / Q000378:metabolism*; D018343:Receptors, Adrenergic, beta-2 / Q000187:drug effects* / Q000502:physiology
D018343:Receptors, Adrenergic, beta-2; D007545:Isoproterenol; D006221:Halothane; D009638:Norepinephrine