EDHF and Vascular Control

• Status: Not yet recruiting
• Trial end date: 2024-01-01
• Target enrollment: 0
• Participant gender: All

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

• Phase: Phase 4
• Accepts Healthy Volunteers?: Accepts Healthy Volunteers

Details

• Lead Sponsor: University of Oklahoma
• Treatments: Fluconazole

Criteria

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, Phenytoin, Lonafarnib

• Cardiometabolic medication use (e.g. anti-hypertensives, insulin-sensitizing, statins)

• Sex hormone replacement medical use (e.g. testosterone, estrogen, progesterone)

• Pregnancy