Role of CGRP in control of skin blood flow during local heating.

The role of calcitonin gene-related peptide (CGRP) in the vasodilator response to local heating of human skin was examined in 24 subjects. Each subject were instrumented with three intradermal microdialysis probes 1 cm apart in the dorsal forearm skin with local skin temperature controlled with a peltier unit (9 cm2) at 34°C. After the trauma induced dilation was resolved (120 min) local skin temperature was manipulated for 50 min in one of four ways: step increase to 38°C (0.1 °C/sec, n=5), step increase to 42°C (n=7), pulsed increase to 38°C (1 pulse per min, 30 sec duration,≈Δ 0.5°C/sec, n=5), and pulsed increase to 42°C (≈Δ1.0°C/sec, n=7). Skin blood flow (SKBF, laser Doppler) was recorded directly over the middle microdialysis probe and the dialysate from all three probes were collected at 34°C and during skin heating and analyzed for CGRP (EIAH). The SKBF response is reported as % of maximal SKBF determined by perfusion with 28 mM SNP at the end of the protocol. CGRP in the dialysate at 34°C averaged 6.3 ± 0.4 pg/ml and SKBF averaged 19.0 ±1.2% max. A step increase in skin temperature to 38 and 42°C produced a plateau SKBF at 50 min of 56.2 ± 4.5 and 80.4 ± 2,7% max, respectively (42°C >38°C, p<0.05) while dialysate CGRP was unchanged at 6.6 ± 0.8 pg/ml (p<0.05). During pulsed heating the plateau SKBF was attenuated averaging only 31.1 ± 6.4 and 63.3 ± 4.2 % max for 38 and 42°C, respectively (p<0.05). In addition, dialysate CGRP levels were reduced to 3.7 ± 0.7 pg/ml (p<0.05) during pulsed heating. A strong relationship between thermal load (°C·min) and the magnitude of the secondary rise in SKBF (r = 0.954, p<0.05) points to an important role of local thermosensitive receptors (i.e. TRPV receptors), rather than CGRP release, in regulating this nitric oxide mediated cutaneous dilation. (NIH HL039818)