Red Blood Cell ATP Release and Vascular Function in Humans

Participants will initiate contact with the investigators by responding to flyers placed in the community either by phone or email. The first correspondence (phone or email) will provide a brief description of the research and ask a series of screening questions to determine age, height, weight, and any medications participants may be taking as well as the current health status (diagnoses, basic health history, and physical activity level) of participants. If they qualify, a two hour screening visit is scheduled during a time when the participant will be examined by the physician. All participants will undergo informed consent in a face to face private meeting with the research coordinator. Following informed consent, participants will be evaluated by a physician and undergo a treadmill stress test to rule out cardiovascular disease.

During the study, heart rate will be monitored with a 3-lead ECG and blood pressure will be monitored noninvasively with a blood pressure cuff on the finger (finometry). Venous blood will be collected at multiple time points via a catheter inserted into a forearm vein draining skeletal muscle circulation for measurement of blood gases (0.5 mL/sample) and plasma [ATP] (2 mL/sample), with less than 100 mL of blood being drawn in total (~60mL total). Blood flow at rest and in response to hypoxia and exercise will be measured non-invasively using Doppler ultrasound of the brachial artery. Hypoxia trials will be performed by having participants breathe a low oxygen gas mixture via a mouthpiece that is hooked up to gas tanks and an anesthesia monitor to decrease their oxygen saturation to ~80% (similar to hiking a 14er) for 10 minutes. Exercise trials will last for approximately 15 minutes and will involve participants performing graded-intensity rhythmic handgrip exercise by lifting weights (corresponding to a low, moderate, and high workload) using a pulley system. The drug treatment used in this study (fasudil) is being given because it may improve red blood cell ATP release in older adults. This is a double-blinded placebo controlled study, thus participation will occur on two randomized experimental days.

Inclusion criteria

• Healthy
• Sedentary to moderately active
• 18 to 30 years old for young subjects
• 60 to 80 years old for older subjects

Exclusion criteria

• Obesity (BMI ≥ 30 kg/m^2)
• Cardiovascular disease
• Metabolic disease
• Use of medications that can influence cardiovascular function
• Blood pressure greater than or equal to 140/90
• Smoker
• Use of hormone replacement therapy