Microneedle-assisted iontophoretic transdermal administration of adrenergic antagonists does not modulate palmar sweating induced by static exercise in healthy young adults

Abstract

Palmar sweating is primarily evoked by psychological and physical (e.g., exercise) stress, while the peripheral control of this response remains uncertain. We investigated whether the transdermal administration of adrenergic antagonists modulates palmar sweating induced by isometric knee extension (IKE) exercise. In a climate chamber (28 °C and 40 % relative humidity), 15 healthy young adult males completed IKE exercises at maximal (5 s maximum voluntary contraction, MVC) and submaximal (50 % MVC to exhaustion) effort, before and after the transdermal iontophoretic administration of bretylium (noradrenergic sympathetic nerve inhibitor), terazosin (α-adrenergic receptor antagonist), propranolol (β-adrenergic receptor antagonist), or NaCl (control) to the palm pretreated with solid microneedles to enhance skin permeability. The efficacy of terazosin and propranolol on the palm was assessed by administering α- and β-adrenergic agonists (phenylephrine and salbutamol combined with aminophylline, respectively) in follow-up studies, whereas bretylium efficacy was verified by evaluating cold-induced palmar cutaneous vasoconstriction. Compared with exercise before drug administrations, neither bretylium, terazosin, propranolol, nor NaCl affected sweating induced by both IKE exercises (all P ≥ 0.600, interaction and treatment effect). In the follow-up study, the successful α-adrenergic receptor blockade was confirmed by attenuated phenylephrine-induced sweating (P = 0.001). Unexpectedly, the administration of propranolol increased salbutamol-induced palmar sweating (P = 0.008), leaving the efficacy of β-adrenergic receptor blockade uncertain. The bretylium administration effectively abolished cold-induced cutaneous vasoconstriction (P = 0.006). In conclusion, this study demonstrates that transdermal administration of bretylium, terazosin, and propranolol does not alter palmar sweating induced by IKE exercise, implying the absence of adrenergic modulation.