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Vascular dysfunction is a common factor in many chronic debilitating diseases, contributing to morbidity and mortality. With the onset of chronic disease or exposure to stress, the vasculature displays an inability to adequately respond to increased blood flow demands, manifesting in a reduced ability or altered mechanism of vasodilation. Aging is an independent risk factor in the development of cardiovascular disease, and reduces vasodilator capacity, or alters the mechanism by which vasodilation occurs in multiple vascular beds. Chronic exercise/physical activity is one of the most potent ways to enhance vascular function, resulting in favorable outcomes such as reductions in blood pressure, and improved ability to perform activities of daily living. Barriers to exercise or failure of long-term adherence preclude many populations from the cardiovascular benefits of exercise, thus further enhancing cardiovascular risk. Avenues to mimic blood flow patterns observed with exercise may exert beneficial effects without the need for the ability to exercise. Recent evidence has demonstrated that passive heat therapy, or chronic heat exposure (~ +1°C in core temperature) results in reductions in major adverse cardiovascular events, blood pressure and improved large artery endothelial function, primarily through preservation of large artery function in response to vascular stress. It is unclear whether microvascular function is augmented in response to acute heat exposure, or whether this can protect against vascular insults particularly in older adults. Some preliminary evidence in humans suggest that autophagy, a cell recycling process is involved in the beneficial cardiovascular effects, as short-term heat exposure upregulates markers of autophagy. Previous evidence from our lab indicates that autophagy governs the mechanism by which microvascular vasodilation occurs. The role of autophagy in mediating the beneficial effects of passive heating is unknown.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Passive Heating of lower limbs | Experimental | The lower limbs will be immersed in warm circulating water for 60 minutes. |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Passive Heating | Procedure | The lower limbs will be immersed in warm (42C) circulating water for 60 minutes. |
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| Measure | Description | Time Frame |
|---|---|---|
| Change in cutaneous microvascular function | Change in cutaneous microvascular function assessed via microdialysis infusion of acetylcholine (dose response) in the presence and absence of L-NAME to test the dependency upon NO to elicit vasodilation. | Baseline, 60 minutes post I/R, and 60 minutes post hot water immersion + I/R injury |
| Measure | Description | Time Frame |
|---|---|---|
| Spontaneous baroreflex sensitivity | Change in spontaneous BRS | Baseline, 60 minutes post I/R, 60 minutes post hot water immersion + I/R injury |
| 24-hour (Ambulatory) Blood Pressure | Ambulatory blood pressure (systolic, diastolic) for both peripheral and aortic blood pressure |
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Inclusion Criteria:
Exclusion Criteria:
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| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Medical College of Wisconsin | Milwaukee | Wisconsin | 53226 | United States |
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| ID | Term |
|---|---|
| D019331 | NG-Nitroarginine Methyl Ester |
| ID | Term |
|---|---|
| D001120 | Arginine |
| D024361 | Amino Acids, Basic |
| D000596 | Amino Acids |
| D000602 | Amino Acids, Peptides, and Proteins |
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| L-NAME | Drug | L-NAME will be used during measurement of cutaneous microvascular function to test the dependency upon NO to elicit vasodilation. |
|
| Baseline |
| Change in plasma concentration of heat shock proteins | Change in the plasma concentrations of various heat shock proteins (HSP 70, 90) | Baseline and 60 minutes post hot water immersion |
| D000599 |
| Amino Acids, Diamino |