Halothane selectively attenuates α₂-adrenoceptor mediated vasoconstriction, in vivo and in vitro

The mechanism by which halothane interferes with catecholamine-induced vasoconstriction was examined, utilizing specific agonists at postjunctional α₁- and α₂-adrenoceptors on vascular smooth muscle. Stimulation of either adrenoceptor subtype normally produces vasoconstriction. Two experimental models of drug-induced vasoconstriction were used: 1) in vivo blood pressure response in pithed rats, and 2) in vitro isometric tension development in canine saphenous vein rings. These models were then utilized to examine the anti-vasoconstriction properties of halothane. In vivo, halothane (1 MAC) produced a significant depression in the vascular response to azepexole (an α₂-adrenoceptor agonist), but halothane did not alter vasoconstriction by phenylephrine (an α₁-adrenoceptor agonist). Halothane caused a 24% reduction of maximal response (P < 0.0001) to azepexole in pithed rats, and a 3.2-fold rightward shift of the log dose-response curve (P < 0.0001). Similarly, in vitro, halothane significantly attenuated α₂- but not α₁-adrenoceptor responsivness. Halothane (4%) depressed maximal vein contraction to azepexole by 26% (P < 0.0001), and shifted the log concentration-response curve 2.4-fold to the right (P < 0.0001). The observed selective interference with α₂-mediated vasoconstriction by halothane is unlikely to represent drug antagonism at the receptor level. Our observations may suggest, indirectly, that halothane interferes with Ca⁺² entry into vascular smooth muscle. The phenomenon of selective anti-vasoconstriction at α₂-adrenoceptors by halothane may explain why α₁-adrenergic agonists often appear to retain their vasopressor activity during halothane anesthesia. The mechanism of halothane-induced vasodilation thus includes attenutation of α₂- but not α₁-adrenergic vasoconstriction; this further demonstrates the multifactorial nature of halothane-induced vasodilation.