Selective abolition of adrenergic vasoconstrictor responses in skin by local iontophoresis of bretylium

Skin blood flow (SkBF) in humans is controlled by a noradrenergic active vasoconstrictor system and an active vasodilator system of an uncertain neurotransmitter. Understanding how these systems interact would be aided if the vasodilator system could be studied in the absence of effects of the vasoconstrictor system. To accomplish this we combined laser-Dopper velocimetry (LDV) with the local iontophoresis of bretylium in 10 studies with eight healthy subjects. Each subject had two fore-arm sites (0.64 cm²) treated with bretylium to block local norepinephrine release. LDV was monitored at those sites and at two untreated sites during 3-4 min of cold stress, 35-45 min of heat stress, and a final cold stress to verify blockade. In five studies, local temperature was raised to 39°C at the LDV sites before the final cord stress. Whole body skin temperature was controlled by water-perfused suits. Mean arterial pressure (MAP) was measured noninvasively. Heart rate and internal temperature were also recorded. Cutaneous vascular conductance (CVC) was calculated as LDV/MAP. During the initial cold stress, performed 130 min after bretylium treatment, CVC at treated sites fell by an average of 0.3 ± 3.2% (P > 0.10) and at untreated sites by 29.2 ± 4.1% (P < 0.001 between sites). During heat stress, CVC at treated sites rose by 419 ± 66% and at control sites, by 517 ± 90% (P > 0.10 between sites). The internal temperature threshold for cutaneous vasodilation was not statistically different between sites (P > 0.10). In the final cold stress, performed an average of 238 min after bretylium treatment, CVC at treated sites without local warming fell by 6.4 ± 2.8% (P > 0.05) and at untreated sites by 21.8 ± 3.9% (P < 0.05). In studies with local temperature raised to 39°C, CVC at treated sites fell by 1.3 ± 2.2% (P > 0.10) and at untreated sites by 41.6 ± 9.2% (P < 0.05) during the final cold stress. In both conditions, the decreases in CVC during cold stress were significantly less than those at untreated sites (P < 0.01). Cold-induced reflex vasoconstriction was blocked successfully by bretylium treatment, whereas the active vasodilator response to heat stress was not affected. The final periods of cold stress verified that significant blockade persisted beyond 3 h. We conclude that the combination of bretylium iontophoresis with LDV can be used to separate active vasoconstrictor and active vasodilator control of the human cutaneous circulation.