Evidence for the existence of vascular alpha 2-adrenergic receptors in humans.

Many studies have suggested that alpha-adrenergic receptors on vascular smooth muscle are heterogeneous and that both alpha 1- and alpha 2-adrenergic receptors can cause vasoconstriction when stimulated. We explored this hypothesis in normal humans by comparing the capacity of yohimbine, an alpha 2-adrenergic receptor antagonist, and prazosin, an alpha 1-adrenergic receptor agonist, with differentially blocked pressor responses to phenylephrine, an alpha 1-adrenergic receptor agonist, and epinephrine, a nonselective alpha-agonist. We studied these responses in normal male volunteers who had been pretreated with propranolol (80 mg orally every 8 hours for 5 days) to obviate stimulation of beta-receptors by either agonist. We found differential effects of the antagonists on responses to the two agonists. Yohimbine induced a 3.1-fold (+/- 0.5) shift in the dose of epinephrine, which raised blood pressure 25 mm Hg, and only a 1.9-fold (+/- 0.2) shift in the response to phenylephrine (p less than 0.01). Prazosin induced a 2.4-fold (+/- 0.5) shift in the responses to epinephrine and a 4.5-fold (+/- 1.2) shift in the response to phenylephrine (p less than 0.05). These data are consistent with the notion that alpha-adrenergic receptors in the human vasculature are not homogeneous, but rather may be subdivided into at least two subtypes, one resembling alpha 1-adrenergic receptors and the other resembling alpha 2-adrenergic receptors.