Does local heating-induced nitric oxide production attenuate vasoconstrictor responsiveness to lower body negative pressure in human skin?

We tested the hypothesis that local heating-induced nitric oxide (NO) production attenuates cutaneous vasoconstrictor responsiveness. Eleven subjects (6 men, 5 women) had four microdialysis membranes placed in forearm skin. Two membranes were perfused with 10 mM of N^G-nitro-L-arginine (L-NAME) and two with Ringer solution (control), and all sites were locally heated to 34°C. Subjects then underwent 5 min of 60-mmHg lower body negative pressure (LBNP). Two sites (a control and an L-NAME site) were then heated to 39°C, while the other two sites were heated to 42°C. At the L-NAME sites, skin blood flow was elevated using 0.75-2 mg/ml of adenosine in the perfusate solution (Adn + L-NAME) to a similar level relative to control sites. Subjects then underwent another 5 min of 60-mmHg LBNP. At 34°C, cutaneous vascular conductance (CVC) decreased (Δ) similarly at both control and L-NAME sites during LBNP (Δ7.9 ± 3.0 and Δ3.4 ± 0.8% maximum, respectively; P > 0.05). The reduction in CVC to LBNP was also similar between control and Adn + L-NAME sites at 39°C (control Δ11.4 ± 2.5 vs. Adn + L-NAME Δ7.9 ± 2.0% maximum; P > 0.05) and 42°C (control Δ1.9 ± 2.7 vs. Adn + L-NAME Δ 4.2 ± 2.7% maximum; P > 0.05). However, the decrease in CVC at 42°C, regardless of site, was smaller than at 39°C (P < 0.05). These results do not support the hypothesis that local heating-induced NO production attenuates cutaneous vasoconstrictor responsiveness during high levels of LBNP. However, elevated local temperature, per se, attenuates cutaneous vasoconstrictor responsiveness to LBNP, presumably through non-nitric oxide mechanisms.