Endothelial Derived Hyperpolarization Factor and Vascular Control

Description

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

Conditions

Healthy

Study Overview

Study Details

Study overview

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

Endothelial Derived Hyperpolarization Factor and Regulation of Cerebral and Muscle Blood Flow

Endothelial Derived Hyperpolarization Factor and Vascular Control

Condition
Healthy
Intervention / Treatment

-

Contacts and Locations

Norman

Department of Health and Exercise Science, Norman, Oklahoma, United States, 73019

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

For general information about clinical research, read Learn About Studies.

Eligibility 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)
  • * 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

Ages Eligible for Study

18 Years to 30 Years

Sexes Eligible for Study

ALL

Accepts Healthy Volunteers

Yes

Collaborators and Investigators

University of Oklahoma,

Jeremy M Kellawan, PhD, PRINCIPAL_INVESTIGATOR, University of Oklahoma

Study Record Dates

2025-05