Evidence for Postjunctional Vascular α2-Adrenoceptors in Peripheral Vascular Regulation in Man

Preliminary studies in healthy normotensive subjects with a selective alpha 2-adrenoceptor antagonist 2-[2-(1,4-benzodioxanyl)]-2-imidazoline (RX781094) in a dose of 0.2 microgram/kg intravenously are described. There was a transient increase in blood pressure, and plasma noradrenaline, 10-20 min after dosing and an associated reduction in heart rate. These observations are consistent with blockade of peripheral presynaptic alpha 2-adrenoceptors in man. The pressor responses to alpha-methylnoradrenaline, which has relatively selective agonist effects on alpha 2-adrenoceptors, were markedly attenuated between 0.5 and 3.0 h after dosing (dose ratio greater than 20). The pressor responsiveness to intravenous phenylephrine, a selective alpha 1-adrenoceptor agonist, was only slightly reduced (dose ratio 1.7 +/- 0.8), as was the blood pressure rise after intravenous noradrenaline (dose ratio 1.7 +/- 0.7). The differential effects on the agonist pressor responses are consistent with antagonism by RX781094 of post-junctional alpha 2-adrenoceptors on vascular smooth muscle.