Postjunctional alpha-adrenoceptors and the regulation of arteriolar tone in humans

The highly selective alpha-adrenoceptor agonists methoxamine (alpha 1) and azepexole (alpha 2), the less selective alpha-adrenoceptor agonists clonidine (alpha 2 greater than alpha 1) and guanfacine (alpha 2 greater than alpha 1), and the highly selective antagonists doxazosin (alpha 1) and yohimbine (alpha 2) were used to study post-junctional alpha-adrenoceptor subtypes in human blood vessels. Studies were done in healthy volunteers. All drugs were given intraarterially, and changes in forearm blood flow were measured by plethysmography. All agonists produced a significant and dose-dependent vasoconstriction. The effect of azepexole was abolished by yohimbine but hardly influenced by doxazosin. The reverse was found for methoxamine. The clonidine and guanfacine-induced vasoconstriction was partly prevented by both antagonists. Single infusions of doxazosin and yohimbine gave significant vasodilation. It is concluded that post-junctional alpha 1-and alpha 2-adrenoceptors are present in human blood vessels and contribute to basal vascular tone. In a second study, it was shown that both alpha-adrenoceptor subtypes are involved in the vasoconstrictor effect of exogenous adrenaline and noradrenaline. No preference was found of either catecholamine for the postjunctional alpha 1-and alpha 2-adrenoceptor.