Two distinct α1‐adrenoceptor subtypes involved in noradrenaline contraction of the rabbit thoracic aorta

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Abstract
Recently, α1‐adrenoceptors in blood vessels have been classified into three subtypes (α1H, α1L and α1N). We examined which subtype (or subtypes) is involved in the noradrenaline‐induced contraction of rabbit thoracic aorta. Noradrenaline produced a concentration‐dependent contraction in the rabbit isolated thoracic aorta. Prazosin antagonized the contractions to noradrenaline, resulting in a rightward displacement of the concentration‐response curve. However, the shift was not proportional to the concentration of prazosin; Schild plots showed that the inhibition by prazosin was biphasic, implying that noradrenaline acted through two receptor populations. Two affinity constants (pKB values of 10.02 and 8.83) were determined for prazosin at these sites. However, under continuous treatment with 1 nm prazosin, or in strips pretreated with chlorethylclonidine (CEC; an α1H inactivating agent) to remove the contribution of one receptor population, prazosin showed a single pKB or pA2 value of approximately 8.3. Yohimbine also produced biphasic antagonism of noradrenaline‐induced contractions, resulting in two affinity constants (pKB = 6.52 and 6.17). However, a monophasic Schild plot was obtained for yohimbine either in the presence of 1 nm prazosin (pA2 = 6.08) or in strips pretreated with CEC (pA2 = 6.03). The Schild plot for HV723 (a selective α1N‐antagonist) yielded a monophasic slope (pKB = 8.47) and the inhibition was not affected by 1 nm prazosin or CEC‐pretreatment. [3H]‐prazosin bound to α1‐adrenoceptors of the aortic membrane preparations with two different affinities (pKD = 9.94 and 8.37). The high but not the low affinity site was completely masked by 1 nm prazosin and inactivated by pretreatment with CEC. These results strongly suggest that noradrenaline‐induced contraction of the rabbit thoracic aorta is mediated through two distinct α1‐adrenoceptor subtypes, designated α1H and α1L.