Age Comparisons of Exercising Muscle O2 Supply in Healthy Adults: Effects of Esmolol Infusion

This study will test the central hypothesis that postmenopausal women will demonstrate increased oxygen extraction in active leg muscle during leg cycling exercise while receiving an infusion of Esmolol, a fast-acting β1 selective antagonist, when compared to premenopausal women. β1 selective antagonists (or "β1 blockers") are used to lower heart rate and improve O2 supply-to-demand balance in patients with coronary artery disease. By using esmolol to attenuate the central sympathetic response to exercise (increased heart rate and cardiac output) we can examine peripheral mechanisms of O2 delivery. The current project will evaluate how older postmenopausal women adjust active muscle O2 supply to an acute reduction in systemic O2 delivery during large muscle dynamic exercise when compared to younger premenopausal women.

3.1 Inclusion Criteria

• Capable of giving informed consent
• Premenopausal women ages 18-35 years OR post-menopausal women ages 55-70 years
• Satisfactory medical history and physical exam, as determined by a Clinical Research Center (CRC) clinician
• Not currently taking medications affecting heart rate or contractility
• Fluent in written and spoken English

3.2 Exclusion Criteria

Participants who will not be studied are those who:

• Are less than 19 years of age or more than 70 years of age
• Are pregnant or lactating
• Are prisoners or institutionalized individuals or unable to consent
• Diagnosed renal failure (Creatinine >2.0 mg/dl)
• Diagnosed liver disease (ALT and aspartate aminotransferase {AST} 2 times normal)
• Diagnosed Reynaud's disease
• Have uncontrolled diabetes
• Have uncontrolled hypertension
• Have a left ventricular ejection fraction < 40%
• Have a recent history of unstable angina or myocardial infarction (<6 months), unstable angina, or use of nitrate medications within past 2 weeks

• Severe lung disease (i.e., on supplemental oxygen or frequently use rescue inhalers) 11. Diagnosed bleeding or clotting disorder or recent blood transfusion 12. Have asthma, history of thyroid issues or hyperkalemia 13. Known use of recreational drugs 14. Methylphenidate use