Section 1: Background Physiology
What is endothelial function?
The interior lining of human vasculature consists of a single layer of endothelial cells. This endothelial layer plays an important role in the maintenance of vascular function. Vascular function is necessary for the appropriate distribution of blood flow. As illustrated by Poiseuille’s law below, changes in radius will have the greatest impact on blood flow. Changes in radius and consequently flow are the result of a coordinated input of signals from the sympathetic nervous system to vasoconstrict, and signals from the vascular endothelium to dilate(1).
During exercise, increases in sympathetic activity result in systemic vasoconstriction. Blood flow to active muscles during exercise is dependent on the release of factors such as nitric oxide (NO) from the endothelium. NO released from the endothelium of active muscles acts on vascular smooth muscle, resulting in dilation (2, 3). Therefore, proper vascular function is essential for allocation of blood flow during exercise and vascular function is dependent on an intact, functioning endothelium(1).
Effect of shear stress on endothelial function?
Shear Stress = Blood Viscosity x Blood Velocity / Internal Diameter
Exercise is associated with an increase in shear stress. This increase in shear stress is observed in larger conduit and resistance arteries as the production of metabolic byproducts increases in working muscles. These metabolites result in dilation of downstream arterioles (3, 6). As arterioles dilate, blood flow through downstream capillaries and postcapillary venules increases to provide enhanced nutrient delivery and removal of waste products from working muscles (6, 7). This increase in blood flow through arterioles must be matched by an increase in blood flow through the upstream conduit and resistance arteries. This enhances the flow gradient in the arterial system and results in an increase in flow velocity through upstream vasculature. As velocity increases, shear stress on the endothelium increases resulting in NO release from the endothelium (3, 4, 8).
How does blood flow respond to heat?
Exposure to heat results in a rise in core temperature. With core temperature in humans being tightly regulated, small deviations in internal temperature signal the preoptic area of the hypothalamus (9) to initiate thermoregulatory responses. If core temperature reaches 40C or higher tissue damage and heatstroke can occur (10).
To dissipate heat, peripheral and cutaneous blood flow increases following an increase in core temperature. At temperatures above 34C, the primary mechanism for heat loss will be evaporative heat loss or sweating. As blood flow to the skin increases(11), the resultant increase in pressure in cutaneous vascular beds causes fluid shifts to extracellular space and eventually taken into the sweat glands to be secreted (12). The evaporation of sweat from the skin surface results in heat transfer to the environment and consequently cooling of the skin.
This increase in skin blood flow is the result of dilation in cutaneous vascular beds. As peripheral vasculature volume increases, the velocity at which blood passes through upstream arteries is increased, resulting in an increase in shear stress on upstream arteries (14). Like exercise, the increased velocity produces a shear stress on the endothelium of upstream larger arteries, increasing NO production from the endothelium (5, 17).
Section 2: Vascular Function Responses to Passive Heat
If thermoregulatory mechanisms result in an increase in skin blood flow and consequently increases in arterial shear stress, the question arises of whether passive heat treatment could be utilized to elicit similar vascular adaptations seen with exercise. Passive heat treatment has been shown to increase vascular function. Various approaches have been taken to determine the effects of passive heat treatment on vascular function with heat treatment being administered using short wave diathermy, hot water immersion, water perfused suits, as well as heat chambers or saunas.
Brunt 2016 (13) showed that passive heat therapy improves cutaneous microvascular function in sedentary humans via improved nitric oxide-dependent dilation. These improvements in function were assumed in large part to the increase in shear stress associated with heat exposure.
Passive heat treatment has also been shown to improve vascular function in older adults. Romero et al., 2017 (15) showed that shear stress increases in both young and old individuals following passive heat treatment through hot water immersion. While shear rate was significantly increased in both the older and younger individuals, Romero reported that only the old subjects saw an increase in macro and microvascular function. These findings suggest a potential therapeutic role of chronic passive heating to improve vascular health.
A study done by Thomas et al., 2017(16) assessed acute responses to lower limb passive heat using hot-water immersion in patients with peripheral arterial disease. A single bout of lower limb produced significant increases in shear rate and lower limb blood flow in elderly subjects with and without peripheral artery disease.
The key findings represented by these studies are that (i) passive heating results in an increase in artery shear stress. Increased artery shear stress is known to be a potent stimulator of NO release from the endothelium. The ability of the endothelium to release NO in the presence of sympathetic stimuli is indicative of endothelial function, which is essential for proper blood flow distribution. (ii) The positive effects of passive heating are observed in both young individuals and older. Given that age is associated with a decrease in vascular function (more in previous post), passive heating presents itself as a promising mechanism to prevent further decline in vascular function. (iii) Passive heating results in increased shear stress, resulting in increased vascular function in individuals presenting with vascular disease, specifically peripheral arterial disease. Not only is passive heating effective on healthy arteries, but it also elicits a response in disease states. This suggests that passive heat treatment could be utilized for more than just preventative measures. Individuals with peripheral arterial disease often have limited capacity for exercise because of pain associated with claudication (plaque buildup in arteries of the lower extremities). Heat treatment could be used to stimulate the endothelium in these individuals because it increases shear rate independent of exercise.
Vascular function is dependent on the health of the endothelium. Functional endothelium releases NO, allowing for dilation in the affected artery. Shear stress has been shown to be an important stimulus for the release of NO. Existing data suggest heat treatment to be a valid method of improving vascular endothelial health.
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