Endothelial Derived Hyperpolarization Factor and Regulation of Cerebral and Muscle Blood Flow
University of Oklahoma
Summary
Most cardiometabolic diseases are characterized by increased muscle sympathetic nerve activity (MSNA) during rest and exercise which contributes to poor health outcomes. In healthy humans during muscle contraction, there is a blunting of skeletal muscle vascular responsiveness to increases in MSNA. However, the exact mechanisms involved are unknown although, best evidence suggests that the mechanism is endothelium derived, but nitric oxide (NO) and prostaglandin (PG) independent. Endothelium-derived hyperpolarizing factor (EDHF) is a NO and PG independent vasodilator in both cerebral and skeletal muscle circulations, however, it is unknown if EDHF contributes to vascular responsiveness during elevated MSNA. The application of lower body negative pressure (LBNP) is a safe and non-invasive manipulation that can be used to increase MSNA causing vasoconstriction in humans. Therefore, the purpose of this experiment is to determine if acute inhibition of EDHF alters central and peripheral vascular responses to LBNP at rest and during dynamic exercise. Thereby, providing evidence by which EDHF contributes to vascular control in healthy humans and identify it's potential as a therapeutic target for cardiometabolic diseases that are characterized by elevated MSNA
Description
The purpose of this study is to investigate the importance of the endothelium-derived hyperpolarizing factor (EDHF) in regulation of muscle and brain blood flow during rest, sympathetic activation via lower body negative pressure (LBNP), and during rhythmic exercise. We hypothesize that acute inhibition of EDHF will blunt cardiovascular responses and decrease peripheral tissue oxygenation (specifically in the brain and muscle) in response to LBNP during rest and during exercise. This work will provide evidence that EDHF counter acts sympathetic nervous activity in healthy humans, thereby highl…
Eligibility
- Age range
- 18–30 years
- Sex
- All
- Healthy volunteers
- Yes
Inclusion Criteria: * Normotensive (systolic blood pressure \< 130 mmHg and/or diastolic blood pressure \< 85 mmHg) individuals * Individuals free of cardiovascular disease and metabolic disease * Individuals free of any form of autonomic dysfunction * Individuals with a BMI under 30 kg/m² * Women that are premenopausal with a regular menstrual cycle (26-30 days) Exclusion Criteria: * Smokers, tobacco users (regular use in the last 6 months) * Individuals with a blood pressure greater than 130/85 * Subjects who use Amiodarone, Sulphaphenazole * Subjects who use S-warfarin, Tolbutamine, Phen…
Interventions
- DrugFluconazole 150 mg
A single acute 150 mg dose
Location
- Department of Health and Exercise ScienceNorman, Oklahoma