Evidence for nNOS Participation in Cutaneous Active Vasodilation in Humans

Nitric oxide (NO) participates in cutaneous active vasodilation (AVD) during heat stress (HS) in humans. We hypothesized neuronal nitric oxide synthase (nNOS) and endothelial nitric oxide synthase (eNOS) are the sources of nitric oxide (NO) in HS. We compared effects of a specific nNOS inhibitor, 7‐NI, with a non‐specific NOS inhibitor, L‐NAME(LNM) on AVD during HS. 3 intradermal microdialysis probes (MD) were inserted into forearm skin. 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 5% DMSO/Ringer's at all sites, followed by 20mM LNM or 2mM 7‐NI dissolved in 5% DMSO/Ringer's at 2 separate MD sites. 5% DMSO/Ringer's was continuously perfused at the 3rd control site (CTR). The protocol began with 40 minutes of normothermia followed by a 3 minute of whole body cooling after which whole body heating was performed to effect HS and activate AVD. After HS, 58mM sodium nitroprusside was perfused through all MD sites to maximize vasodilation for data normalization. Results: there were no differences between sites during normothermia. Both LNM and 7‐NI attenuated the rise of CVC during HS (p= or < 0.001, L‐NAME or 7‐NI vs CTR) but only LNM showed delay of the onset of vasodilation. There was no significant difference between LNM and 7‐NI at the peak of HS (p=0.083) on CVC. Given that blockade of both eNOS and nNOS by LNM delayed and attenuated AVD‐mediated increases in CVC, whereas blockade of nNOS by 7‐NI only attenuated the CVC increase, we conclude that eNOS generation of NO occurs early in HS, but that the nNOS isoform contribute to NO production in late HS.