CGMP is involved in Cutaneous Vasodilation in Local Skin Warming in Humans

Abstract

Nitric oxide (NO) dependent systems typically involve cGMP generation via NO activation of soluble guanylyl cyclase(sGC) as a step in vasodilation. We hypothesize that this mechanism participates in the vasodilation induced by increased local skin temperature (Tloc). We examined effects of a specific sGC inhibitor, ODQ, on increases in skin blood flow (SkBF) caused by increased Tloc. 3 intradermal microdialysis probes (MD) were inserted into forearm skin in 11 subjects. Skin blood flow was monitored by Laser‐Doppler Flowmetry (LDF). Local temperatures at the MD sites were controlled by specialized LDF probe‐holder/local‐heater units. The study began with perfusion of Ringer's at all sites, followed by 2%DMSO in Ringer's or 1mM ODQ dissolved in 2%DMSO/Ringer's at 2 separate MD sites. (Preliminary studies showed that 1mMODQ antagonized NO mediated vasodilation by sodium nitroprusside.) Ringer's was continuously perfused at the 3rd control site (CTR). In the protocol, Tloc was initially held at 34°C and then was raised to 41.5°C to cause local vasodilation. Finally, 58mM nitroprusside was perfused at all MD sites to cause maximal vasodilation for data normalization. Results: no SkBF differences were found between sites with Tloc=34°C (p>0.05 between sites). SkBF rose at all sites as Tloc was increased (p<0.05 vs Tloc=34C)). SkBF increase was attenuated at the ODQ treated site with Tloc=41.5°C (p<0.01 vs Ringer's or 2%DMSO sites). These data suggest that sGC activation participates in the vasodilation induced by increased local skin temperature. (supported by NIH Grant HL065599)