Inclusion Criteria:
Young and Older Healthy Adults:
- Males and females willing and able to provide informed consent
- Aged between 18-35 years (Young) or 60-80 years (Older)
- Premenopausal women will be tested within 1-4 days after menses begins to control for hormone status
- Women taking oral contraceptives will be allowed to participate and they will be tested in the low hormone or placebo phase
- Postmenopausal women (at least 12 months since last menstrual cycle) who are not on hormone replacement therapy will be eligible
- Sedentary or recreationally active
- Non-tobacco/nicotine users (e.g., cigarettes, chewing tobacco, nicotine gum or patches)
- Laboratory measured systolic blood pressure <140 mmHg and diastolic blood pressure <90 mmHg
- Normal 12-lead ECG (reviewed by a physician)
- Normal clinical results from a medical exam reviewed by a board certified physician (e.g., Medical & Behavioral Health Questionnaire - see attached document)
- Body mass index (BMI) <40 kg/m2 unless athletic/muscular build; calculation = body weight (kg)/height (m2); this criteria is used to ensure subjects will fit inside the LBNP chamber
- Females only: documentation of a negative pregnancy test prior to the familiarization and experimental sessions
Young and Older Chronic Smokers of Tobacco Cigarettes:
The same criteria (a-c and e-i above) as Young and Older Healthy Adults, except:
- Chronic smokers of tobacco cigarettes only (i.e., at least 20 pack year use)
Exclusion Criteria:
Young and Older Healthy Adults:
- Age <18 years, or 40-60 years, or >80 years
- Body mass index (BMI) >40 kg/m2 unless athletic/muscular build; calculation = body weight (kg)/height (m2)
- Regular tobacco/nicotine users within the last 6 months (e.g., cigarettes, chewing tobacco, nicotine gum or patches)
- Not abstaining from the following 24 hours prior to the familiarization session and the experimental session: exercise, alcoholic substances, prescription or non-prescription medications (unless cleared by the medical screener), dietary supplements, herbal medications, caffeinated substances (including coffee, tea (iced or hot), caffeinated energy drinks or sodas).
- Not fasted for at least 3-4 hours prior to the experimental sessions.
- Positive pregnancy test
- Hormone replacement therapy (males and females)
- Females with an erratic/irregular menstrual cycle
- Females who are using a continually-releasing hormonal (e.g., NuvaRing™ or other hormone-releasing vaginal rings, Depo Provera shot, birth control implants such as Nexplanon) and who do not have a regular menstrual cycle
- Use of prescription drugs, non-prescription drugs or herbal medicines known to alter autonomic function unless cleared prior to the study
- Any metabolic disease, except individuals who are on cholesterol-lowering medications (older subjects only; young subjects on cholesterol-lowering medications will be excluded)
- Use of two or more anti-hypertensive medications (older subjects only; young subjects on anti-hypertensive medications will be excluded)
- Use of beta blockers
- Frequent use of bronchodilators
- Use of anti-coagulant therapy
- Current or past history of hyperthyroidism, or other thyroid hormone-related disease
- Signs of cardiovascular abnormalities (e.g., resting systolic blood pressure >140 mmHg or diastolic blood pressure >90 mmHg; abnormal 12-lead ECG)
- History of cerebrovascular abnormalities (e.g., prior stroke, transient ischemic attacks, epilepsy)
- Known history of atherosclerosis of the carotid arteries (i.e., plaque formation)
- Known history of peripheral artery disease (PAD)
- Concussion and or other loss of consciousness within the past 30 days.
- Autonomic dysfunction (e.g., Shy-Drager Syndrome, Bradbury-Eggleston syndrome, sinus arrhythmia, idiopathic orthostatic hypotension, fainting disorder)
- Respiratory illnesses (e.g., chronic asthma (including exercise-induced asthma), Chronic Obstructive Pulmonary Disease, Reactive Airway Disease)
- History of anaphylaxis
- History of pre-syncopal/syncopal episodes or orthostatic hypotension
- Donated blood within the last 60 days
- History or family history of abnormal blood clotting, clots in deep veins in the legs or pelvis, or blood clots to the lungs
- Known or suspected abdominal hernia
- History of alcohol or drug abuse which inhibits the subject's ability to complete this study
- Known depression, anxiety, or any other mental health issue which inhibits the subject's ability to complete this study
Young and Older Chronic Smokers of Tobacco Cigarettes
The same criteria (a-b and d-dd above) as Young and Older Healthy Adults, except:
- Less than 20 pack year use of tobacco cigarettes, or regular use of other tobacco/nicotine products within the last 6 months (e.g., electronic cigarettes, chewing tobacco, nicotine gum or patches).