FUNCTIONAL ASSESSMENT OF α 1 ‐ADRENOCEPTOR SUBTYPES IN PORCINE CORONARY ARTERY

SUMMARY 1.α 1 ‐Adrenoceptors are known to play an important role in vasoconstriction in response to adrenergic stimulation. However, the functional importance of α 1 ‐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 (pA 2 10.27 and 9.03, respectively). In contrast, the selective α 2 ‐adrenoceptor antagonist yohimbine had a low affinity (pA 2 6.13). Two selective α 1A ‐adrenoceptor antagonists, WB 4101 and 5‐methyl urapidil, were potent and competitive antagonists of α 1 ‐adrenoceptor‐induced contraction (pA 2 10.67 and 8.90, respectively) and the selective α 1D ‐adrenoceptor antagonist BMY 7378 had a low affinity (pA 2 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 pA 2 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.