Soluble Guanylyl Cyclase and Cutaneous Active Vasodilation During Heat Stress 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 hypothesized this mechanism participates in cutaneous active vasodilation(AVD) during whole body heat stress(HS). We examined effects of a specific sGC inhibitor, ODQ, on AVD during HS. 3 intradermal microdialysis probes(MD) were inserted into forearm skin in 7 subjects. Skin blood flow was monitored by Laser‐Doppler Flowmetry(LDF). Body temperature was controlled with water‐perfused suits. Blood pressure was monitored by Finapres and cutaneous vascular conductance calculated(CVC=LDF/MAP). 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). The protocol began with 40 minutes of normothermia followed by 3 minutes of cold stress(CS) after which whole body heating was performed to effect HS and activate AVD. After HS, 58mM SNP was perfused through all MD sites to maximally vasodilate for data normalization.Resultsthere were no differences between sites during normothermia. No differences were found between sites in normothermia or CS. There was no significant difference between Ringer's and DMSO sites at the peak of HS on CVC. ODQ tended to attenuate the maximal CVC achieved at the peak of HS(p=0.0536 vs CTR and DMSO). Blockade sGC by ODQ tended to attenuate AVD during HS, these data suggest that sGC activation participates in AVD.