Abstract:
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.
Description:
64 pages. A thesis presented to the Department of Human Physiology and the Clark Honors College of the University of Oregon in partial fulfillment of the requirements for degree of Bachelor of Science, Spring 2016.