beta-Receptor agonist activity of phenylephrine in the human forearm

Phenylephrine is generally regarded as a "pure" alpha (1)-agonist. However, after treatment of the forearm with the alpha -adrenergic-blocking drug ph entolamine, brachial artery infusion of phenylephrine can cause transient f orearm vasodilation. To determine whether this response was beta -receptor mediated, phenylephrine, phentolamine, and propranolol were infused into th e brachial arteries of six healthy volunteers. Forearm vascular conductance (FVC) was also calculated and expressed as arbitrary units (units). Infusi on of phenylephrine by itself (0.5 mug.dl forearm volume(-1).min(-1)) cause d a sustained decrease (P < 0.05) in FVC from 3.5 +/- 0.7 to 0.9 +/- 0.2 un its (P < 0.05). Infusion of the alpha -blocker phentolamine increased (P < 0.05) baseline FVC to 5.7 +/- 1.3 units. Subsequent infusion of phenylephri ne after <alpha>-blockade caused FVC to increase (P < 0.05) for <similar to >1 min from 5.7 +/- 1.3 to a peak of 13.1 +/- 1.8 units. Propranolol had no effect on baseline flow, and subsequent phenylephrine infusion after alpha - and beta -blockade caused a small, but significant, sustained decrease in FVC from 5.1 +/- 1.0 to 3.6 +/- 0.8 units. There were no systemic effects from the infusions, and saline infusion at the same rate (1-2 ml/min) had n o forearm vasoconstrictor or dilator effects. These data indicate that in h umans phenylephrine can exert transient beta (2)-vasodilator activity when its predominant alpha -constrictor effects are blocked.