FUNCTIONAL ASSESSMENT OF α1-ADRENOCEPTOR SUBTYPES IN PORCINE CORONARY ARTERY

1.α₁-Adrenoceptors are known to play an important role in vasoconstriction in response to adrenergic stimulation. However, the functional importance of α₁-adrenoceptor subtypes at the epicardial coronary artery remains unclear. We examined α-adrenoceptor subtypes by comparing functional affinities for α-adrenoceptor antagonists on noradrenaline (NA)-induced vasoconstriction in porcine denuded right coronary arteries. 2. Noradrenaline induced a dose-dependent vasoconstriction in incubated vessel rings. Prazosin and phentolamine were potent and competitive antagonists for NA-induced contraction (pA₂ 10.27 and 9.03, respectively). In contrast, the selective α₂-adrenoceptor antagonist yohimbine had a low affinity (pA₂ 6.13). Two selective α_1A-adrenoceptor antagonists, WB 4101 and 5-methyl urapidil, were potent and competitive antagonists of α₁-adrenoceptor-induced contraction (pA₂ 10.67 and 8.90, respectively) and the selective α_1D-adrenoceptor antagonist BMY 7378 had a low affinity (pA₂ 6.06). Noradrenaline-induced contraction was insensitive to the alkylating effects of chlorethyl-clonidine. These observations indicate that the vasoconstriction is predominantly mediated by the α_1A-adrenoceptor subtype. This was also supported by a good correlation between pA₂ values from the present study and reported binding affinities (pK_i) of various α-adrenoceptor antagonists with cloned human α_1A-adrenoceptors (r= 0.98), but not for α_1B- or α_1D-adreno-ceptor subtypes (r= 0.77 and 0.41, respectively). 3. Our results indicate that the α_1A-adrenoceptor is the main functional receptor subtype in porcine denuded coronary arteries.