The effect of iontophoresis on the cutaneous vasculature: Evidence for current-induced hyperemia

Combining laser-Doppler blood flux measurements of the skin microcirculation with iontophoresis of vasoactive agents is a promising noninvasive tool for pharmacological studies. However, preliminary observations in our laboratories suggested significant current-associated vasodilation when an expected vasoconstrictor (N^G-monomethyl-L-arginine acetate) was iontophoresed. The present study was designed to define nonspecific current-related versus specific pharmacological effects of iontophoretically administered ions on the cutaneous vasculature. Dose-response studies to a series of anions (nitrite, chloride, acetate, and bicarbonate) and cations (sodium, lithium, and acetylcholine) were carried out in six healthy volunteers (three male) by iontophoresis to the forearm skin on separate days. Laser-Doppler flux was measured at the same sites. All ions caused dose-dependent vasodilation. There was no difference in the response between chloride bicarbonate or acetate and nitrite, thee, the nitric oxide donor, The acetylcholine dose response was shifted rightward after atropine pretreatment. Cutaneous vascular responses to iontophoresis comprise nonspecific, current-induced hyperemia and specific effects of the administered agent. Acetylcholine appears to cause muscarinic and current-induced dilatation. Nitrite may cause current-induced hyperemia alone. Current-induced hyperemia should be considered in interpreting the acute cutaneous vascular responses to iontophoretically administered agents in humans.