Role of Acetylcholine in Blood Flow Regulation in Healthy Adults: Effects of Age and Exercise Training

Summary

The overall goal of this study is to address fundamental questions regarding how the molecule acetylcholine interacts with the sympathetic nervous system to regulate blood flow and oxygen delivery to working skeletal muscle in young and older adults. With advancing age, blood vessels supplying active muscle lose their ability to override sympathetic constriction, which limits delivery of oxygen and results in fatigue. Findings from these studies will serve as the foundation for new strategies to improve regional blood flow regulation in older adults and clinical populations, which will increase quality of life and help to preserve functional independence.

Conditions

• Vasoconstriction
• Vasodilation

Interventions

OTHER

Handgrip Exercise Training

Signaling mechanisms that regulate blood flow will be studied before and after 7 weeks of handgrip exercise training with the non-dominant forearm. Training sessions will consist of 30 min of rhythmic contractions using a handgrip exercise device, and participants will complete four training sessions per week.

DRUG

Acetylcholine

Vasodilatory sensitivity to acetylcholine will be assessed in dose-response fashion as a standard test of vascular function. Doses of 0.5, 1.5, and 15 μg/dl forearm volume/min will be infused via a brachial artery catheter for 4 min per dose.

DRUG

Adenosine Triphosphate

Vasodilatory sensitivity to adenosine triphosphate will be assessed during infusion of a dose of 10 μg/dl forearm volume/min administered via a brachial artery catheter over a total of 4 min.

DRUG

Atropine

Atropine will be used to inhibit muscarinic acetylcholine receptors in order to determine the contribution of acetylcholine to vasodilation during exercise. An initial dose of 0.2 mg will be infused via a brachial artery catheter over 3 min, then a maintenance dose of 0.067 mg will be infused over 1 min prior to each of 5 subsequent experimental trials.

DRUG

Phenylephrine

Vasoconstriction to phenylephrine will be used to assess sensitivity to alpha 1 adrenergic stimulation. Phenylephrine will be infused via a brachial artery catheter at 0.125 or 0.25 μg/dl forearm volume/min (18-35 and 60-85 age groups, respectively), adjusted according to forearm blood flow, for a total of 16 min.

DRUG

Sodium Nitroprusside

Sodium nitroprusside will be infused via a brachial artery catheter as a control vasodilator to elevate resting forearm blood flow to a level similar to that during exercise. The dose will be adjusted to match forearm blood flow to a similar level as during handgrip exercise, with an anticipated average dose of 1 μg/dl forearm volume/min. The dose will be infused for a total of 14 min.

Sponsors & Collaborators

• Colorado State University

  lead OTHER

Principal Investigators

• Frank Dinenno, PhD · Colorado State University

Study Design

Allocation

NA

Purpose

BASIC_SCIENCE

Masking

NONE

Model

SINGLE_GROUP

Eligibility

Min Age

18 Years

Max Age

85 Years

Sex

ALL

Healthy Volunteers

Yes

Timeline & Regulatory

Start

2019-04-16

Primary Completion

2021-07-31

Completion

2021-07-31

FDA Drug

Yes

Countries

• United States

Study Locations