In vivo studies on alpha-adrenergic receptor subtypes in human veins.

We studied in vivo responsiveness of venous alpha 1- and alpha 2-adrenoceptors, measuring the diameter changes in superficial veins in response to alpha-adrenergic agonists and antagonists in healthy human volunteers. The dorsal hand vein technique was used because it permits complete dose-response studies of venous constriction without confounding reflex alterations. Local infusions of all agonists studied induced dose-dependent contraction of the hand vein; the maximal effects (Emax) were: norepinephrine (88% +/- 10%), methoxamine (97% +/- 5%), phenylephrine (95% +/- 6%), clonidine 54% +/- 12%), and azepexole (68% +/- 26%). Clonidine reduced the norepinephrine-induced venoconstriction by 11% +/- 10%. Oral doses of 1 mg prazosin antagonized the venoconstriction induced by norepinephrine, methoxamine, and clonidine, but not by azepexole. Yohimbine-antagonism was observed against all agonists studied. Inhibition by yohimbine of clonidine-induced venoconstriction was irreversible over 60-180 min. Results show that the in vivo effects on veins of alpha-adrenergic agonists are in good agreement with results from in vitro experiments. Agonists with alpha 1- and alpha 2-adrenoceptor subtype selectivity cause venoconstriction in vivo, but alpha 2-receptor mediated constriction is intrinsically weaker. Clonidine acts as a partial antagonist against norepinephrine, presumably on postsynaptic alpha 2-receptors. At high doses, alpha 2-adrenoceptor subtype selectivity of clonidine and yohimbine appear to be partially lost in vivo.