In search of mediators of skin vasodilation induced by transcutaneous nerve stimulation: III. Increase in plasma VIP in normal subjects and in Raynaud's disease.

Previous studies have shown that the widespread and sustained cutaneous vasodilation which can be induced by low-frequency transcutaneous nerve stimulation (TNS) in humans is dependent on a central serotonergic pathway leading to peripheral sympatho-inhibition. In addition, in a bioassay study, the release of a peripheral vasodilator was suggested. However, the TNS-induced dilator response was not blocked by antagonists to a series of known endogenous vasodilators. In the present study another candidate, the vasoactive intestinal polypeptide (VIP) was monitored by means of a specific radioimmunoassay. The results showed an increase in plasma VIP from 5.6 pmol X l-1 before TNS to 7.3 pmol X l-1 after TNS (median values for 15 normal volunteers; P less than 0.05 for the 30% increase). Patients with Raynaud's disease displayed lower levels of VIP than the normal group (median 3.7 pmol X l-1 for 20 patients; P less than 0.01 for the difference from normals). TNS-induced rewarming of the extremities in Raynaud patients was paralleled by 35% increase in plasma VIP (median 5.0 pmol X l-1; P less than 0.01 for the TNS-dependent increase). The results suggest that the TNS-induced increase in plasma VIP parallels the increase in skin temperature in the extremities. However, a causal relationship between the increase in plasma VIP and cutaneous vasodilation remains to be determined. Possible origins of the TNS-dependent increase in plasma VIP are discussed.