In search of mediators of skin vasodilation induced by transcutaneous nerve stimulation: I. Failure to block the response by antagonists of endogenous vasodilators.

Low-frequency transcutaneous nerve stimulation (TNS) produces marked and widespread increases in skin temperature in ischaemic limbs of patients with Raynaud's disease and diabetic polyneuropathy. The prolonged time course of the temperature rise, which is due to increased cutaneous microcirculation, indicates the involvement of a long-lasting neurohumoral substance or metabolite. The vascular response is insensitive to conventional low doses of naloxone (Kaada, 1982a). In the present study the possible release of known endogenous vasodilators, all operating through the sympathetic nerves (Fig. 1, Nos 2-8), have been tested in patients by employing selective pharmacological antagonists or inhibitors to see if the stimulation-induced vasodilation could be blocked. The response was not antagonised either by beta-adrenergic, cholinergic, histaminergic, purinergic, or dopaminergic antagonists or by inhibitors of prostaglandins or plasma kinins.