Exogenous ATP abolishes postjunctional α1‐ and α2‐adrenergic vasoconstriction in humans

Abstract

Recent evidence suggests that adenosine triphosphate (ATP) can inhibit vasoconstrictor responses to endogenous norepinephrine release via tyramine, similar to what is observed in contracting muscle. Whether this involves a reduction in postjunctional α‐adrenergic receptor responsiveness is unclear. Therefore, we tested the hypothesis that exogenous ATP can blunt direct postjunctional α‐adrenergic vasoconstriction in humans. We measured forearm blood flow (FBF; Doppler ultrasound) and calculated the vascular conductance (FVC) responses to local intra‐arterial infusions of phenylephrine (α1‐agonist) and dexmedetomidine (α2‐agonist) during moderate rhythmic handgrip exercise, during a control non‐exercise vasodilator condition (adenosine), and during ATP infusion in 7 young adults. Forearm hyperemia was matched across all conditions. Forearm vasoconstrictor responses to direct α1‐receptor stimulation were blunted during exercise vs adenosine (ΔFVC = −11±3% vs −36±5%; P<0.05), and were abolished during ATP infusion (−4±3%). Similarly, vasoconstrictor responses to α2‐receptor stimulation were blunted during exercise vs adenosine (−12±4% vs−37±9%; P<0.05), and were abolished during ATP infusion (−3±5%). We conclude that exogenous ATP abolishes postjunctional α‐adrenergic vasoconstriction, and this involves both α1‐ and α2‐receptor subtypes.Supported by AG‐022337, HL‐087952