NITRIC OXIDE SIGNALLING PATHWAYS FOLLOWING CHRONIC PASSIVE HEAT THERAPY
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CVD is associated with vascular dysfunction and is often mediated by impainnents in nitric oxide (NO), a powerful vasodilator, and increased oxidative stress. Heat shock proteins (HSP), upregulate proteins linked to improving vascular functioning such as endothelial nitric oxide synthase (eNOS) and super oxide dismutase (SOD; an antioxidant). Therefore chronic passive heat therapy (CHT) may help improve cutaneous circulation in the microvasculature. PURPOSE: To investigate the in vivo effects of CHT on cutaneous NO-dependent dilation and to additionally elucidate the mechanisms behind the improvement through in vitro cell cultures. METHODS: 18 subjects were immersed in 40°C water for 8wks, 4-Sx/week to maintain rectal temperature ~38.5°C for 60min. Prior to and following the last bout, two intradennal microdialysis fibers were inserted into the forearm and infused with lactated Ringer's solution (control) and L-NNA, to inhibit eNOS. Local skin heaters were placed at each site over the fiber and heated to 39°C at a rate of 0.1 C/sec, increasing skin blood flow, which was measured using laser-Doppler flowmetry. Data are presented as the change in NO-dependent dilation from Oto 8 weeks. Additionally post-heat therapy serum was collected at least 36h after the last session. Purchased human umbilical vein endothelial cells were cultured and exposed for 24h to either 37°C (control), direct heat at 39°C, or human sera collected at O and 8wks. eNOS, SOD, HSP70, and HSP90 protein expression was detennined using Western blot nonnalized to vinculin loading control. RESULTS: Subjects' NO-dependent dilation increased significantly (p=.0062). There were no improvements in sham subjects. Direct heating increased SOD expression in endoth~lial cells by 1.23±0.10 fold (p=0.045), HSP70 expression by 1.32±0.03 fold (p<0.008), and HSP90 expression by 1.84±0.38 fold (p=0.04), but had no effect on eNOS (l.04±0.04 fold change, (F0.38). Serum exposure increased both eNOS (1.14±0.37 fold change, p<0.002) and SOD expression (l.29±0.09 fold change, p<0.01), with no change in HSP70 (0.98±0.13 fold change, p=0.85) or HSP90 (0.94±0.08 fold change, p=0.51). Thus, CHT should be considered an alternative means for improving cardiovascular health.