Halothane increases epinephrine threshold for the development of slow responses in isolated canine trabeculae

We studied halothane/epinephrine interaction in isolated canine trabeculae using the doses of epinephrine necessary to produce slow responses (epinephrine threshold for the development of slow responses, ETSR) as an indicator. The preparations were depolarized in Tyrode's solution containing 26 mmol/L of KCl, then epinephrine concentrations in the solution were increased in a stepwise manner. Halothane (1%) had no significant effect, whereas 2% and 4% halothane significantly increased the ETSR. alpha 1-Blockade with either 4, 8, or 16 ng/mL of prazosin or 20, 40, or 80 ng/mL of droperidol did not alter the ETSR, whereas beta 1-adrenergic blockade with 8, 17, or 34 ng/mL of metoprolol significantly increased the ETSR. The same trend was observed when either 8 ng/mL of prazosin or 17 ng/mL of metoprolol was given in combination with 2% halothane. Verapamil (5, 10, or 20 ng/mL) increased the ETSR in a dose-dependent manner. These results indicate that halothane decreases rather than increases the sensitivity of slow calcium channels to epinephrine and that any increase above the baseline ETSR after halothane administration cannot be ascribed to halothane/adrenoceptor interaction but rather to calcium entry-blocking effects of halothane. As slow responses are induced by the activation of slow calcium channels, our findings are consistent with known data that halothane can interfere with slow calcium channel conductance.