Red Blood Cell ATP Release and Vascular Function in Humans
Red Blood Cell ATP Release and Vascular Function in Humans
Previous work demonstrates that the red blood cells of older adults do not release a potent
 vasodilator (ATP) as well as the red blood cells of younger adults. The investigators are
 targeting a pathway within the red blood cell using fasudil hydrochloride to determine if
 both the release of ATP from red blood cells and blood flow responses to low oxygen (hypoxia)
 and exercise in older adults can be improved.
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