CGRP release during local skin heating in humans

We tested the hypothesis that the cutaneous vasodilatation accompanying local skin heating is mediated, in part, by the release of calcitonin gene‐related peptide (CGRP). Seven subjects were instrumented with three intradermal microdialysis probes in the dorsal forearm skin and perfused with lactated ringers at 1.5 μl/min. Local skin temperature (Tsk) was controlled in 40 min blocks at 34°C, 36°C, 38°C, 40°C, and 43°C with a computer regulated peltier unit. Skin blood flow (laser Doppler velocemetry) was recorded directly over the middle microdialysis probe and arterial blood pressure was measured from the opposite arm (non‐invasively). The dialysate was collected and analyzed for CGRP (EIA). The vasodilator response in the skin was described in terms of cutaneous vascular conductance (CVC=flux/MAP) and expressed as a % of CVCmax obtained at Tsk= 43°C. Resting CVC at 34°C averaged 25.4 ± 5.3 % of CVCmax. CVC increased to 30.0 ± 5.1 (p<0.05), 39.7 ± 3.3 (p<0.05), and 65.1 ± 3.1 % CVCmax (p<0.05) at a Tsk of 36, 38, and 40°C, respectively. At Tsk=34°C dialysate [CGRP] averaged 9.9 ± 2.0 pg/ml. The dialysate [CGRP] rose modestly with an increase in Tsk and averaged 10.8 ± 2.2, 11.3 ± 2.9, 12.1 ± 2.8 (p<0.05) and 12.7 ± 2.4 (p<0.05) pg/ml at 36, 38, 40, and 43°C, respectively. During Tsk heating CVC rose exponentially as a function of [CGRP] (r 2 =0.98, p<0.05). These data support the hypothesis that control of CVC by Tsk is mediated, in part, by a release of CGRP. In preliminary trials increasing, Tsk to 45°C increased CVC to 178.4 ± 3.5% CVCmax and dialysate [CGRP] to 14.2 ± 2.9 pg/ml. Clearly clamping local skin temperature at 43°C for 40 min does not produce maximal dilation in all subjects. Funded by NIH HL039818