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

Colorado State University (CSU)

Status and phase: Withdrawn; Early Phase 1

Conditions: Vasodilation; Vasoconstriction

Treatments: Drug: Phenylephrine; Drug: Sodium Nitroprusside; Other: Handgrip Exercise Training; Drug: Acetylcholine; Drug: Atropine; Drug: Adenosine Triphosphate

Study type: Interventional

Funder types: Other

Identifiers

NCT03972683

ACh sympatholysis

Details and patient eligibility

About

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.

Full description

The ability of blood vessels to dilate is essential to ensure adequate blood flow and oxygen delivery to active muscle during exercise. With advancing age, exercising muscle loses the ability to overcome vasoconstriction from the sympathetic nervous system, which impairs blood flow and limits exercise tolerance. Thus, understanding the signaling mechanisms that underlie the ability of active muscle to limit sympathetic vasoconstriction will advance our understanding of blood flow regulation in humans and lay the foundation for new strategies to improve blood flow and exercise tolerance in aging and clinical populations.

Therefore, the purpose of this research is to investigate endogenous acetylcholine as an important signaling molecule that regulates blood flow during exercise. The studies will also determine whether a reduced contribution of acetylcholine explains blood flow impairments in older adults. Since exercise training is known to improve acetylcholine signaling, this research will also address whether a handgrip exercise training intervention will improve blood flow regulation. The expected outcomes will provide new insight to the basic physiology underlying vascular control in humans. Furthermore, the findings will provide insight to the age-related decline in blood flow regulation during exercise and will assess the use of an exercise intervention to improve functional outcomes in older individuals.

Participants will be asked to complete several study visits over the course of 8 weeks. Once study eligibility has been determined, participants will report to the Human Performance Clinical Research Laboratory at Colorado State University for a 3 hour visit to assess forearm exercise capacity. In a separate 5 hour visit following an overnight fast, a physician will place a catheter in the brachial artery of the non-dominant arm to assess vascular function. Participants will then complete 7 weeks of handgrip exercise training (four sessions per week) and return to the laboratory for follow-up visits to assess forearm exercise capacity and vascular function.

Sex: All

Ages: 18 to 85 years old

Volunteers: Accepts Healthy Volunteers

Inclusion criteria

• age 18-35 OR 60-85

Exclusion criteria

• recent history of smoking
• body mass index greater than 30
• history of cardiovascular or metabolic disease, including hypertension or diabetes
• medications that may affect outcome measures, such as blood pressure medications or hormone replacement therapy
• high levels of exercise training, particularly with the forearm (such as weightlifting or rock-climbing)

Trial design

Primary purpose: Basic Science

Allocation: N/A

Interventional model: Single Group Assignment

Masking: None (Open label)

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0 participants in 1 patient group

Handgrip Exercise Training Intervention

Experimental group

Description:

Participants will visit the lab for baseline measurements designed to evaluate signaling mechanisms that regulate blood flow. A physician will place a catheter in the brachial artery for pharmacological infusions. The following drugs will be administered to each participant: acetylcholine, adenosine triphosphate, atropine, phenylephrine, and sodium nitroprusside (see Interventions for further details regarding each drug). The order of infusions will be randomized and blood flow will be allowed to return to baseline between each infusion (\~15 min) with the exception of atropine, which will be administered last owing to its longer half-life. Following baseline measurements, participants will complete a 7 week handgrip exercise training intervention, then they will return to the laboratory for post-training measurements. The post-training assessments will be performed in the same manner as the baseline visit; thus, the same drugs will be infused as described above.

Treatment:

Other: Handgrip Exercise Training

Drug: Adenosine Triphosphate

Drug: Atropine

Drug: Acetylcholine

Drug: Sodium Nitroprusside

Drug: Phenylephrine