Forearm vascular alpha 1-adrenergic blockade by verapamil

Area of Science:

• Pharmacology
• Cardiovascular Physiology

Background:

• Phenylephrine is a vasoconstrictor that acts via alpha-1 adrenergic receptors.
• Verapamil is a calcium channel blocker with potential vasodilatory effects.

Purpose of the Study:

• To investigate the effect of verapamil on phenylephrine-induced vasoconstriction in healthy human subjects.
• To determine if verapamil exhibits alpha-1 adrenergic blockade in vivo.

Main Methods:

• Direct brachial artery infusion and strain gauge plethysmography were used to measure forearm blood flow and vascular resistance.
• Subjects received intravenous propranolol for systemic beta-blockade.
• Ascending doses of phenylephrine were administered alone and concurrently with verapamil via brachial arterial infusion.

Main Results:

• Verapamil significantly shifted the phenylephrine dose-response curve to the right (dose ratio of 8.1, p < 0.05).
• Verapamil decreased the y-intercept of the phenylephrine dose-response curve (60.0 vs. 40.3 mm Hg ml/100 ml forearm volume/min, p < 0.05).
• No significant change in the slope of the phenylephrine dose-response curve was observed.

Conclusions:

• Verapamil attenuates phenylephrine-induced forearm vasoconstriction in humans.
• These findings suggest that verapamil possesses in vivo alpha-1 adrenergic blocking activity.
• Verapamil's vasodilatory effects in the forearm are partly mediated by alpha-1 adrenergic blockade.