Stress and the Nervous System

Stress has complex effects on the body's physiology. Models of stress such as hypoglycemia
have identified that stress activates the hypothalamic-pituitary-adrenal (HPA) axis and
sympathoadrenal system acutely. Additionally, there are delayed effects of prior exposure to
hypoglycemia. The day after being exposed to a hypoglycemic stimulus there are: 1) decreases
in the catecholamine release to a new hypoglycemic stress; 2) decreases in the muscle
sympathetic nerve activity (MSNA) response to either a new hypoglycemic challenge or
transient hypotension; 3) decreases in cardiac vagal baroreflex sensitivity (BRS); and 4)
increases in sensitivity to thermal pain and altered temporal summation (decreased tolerance
to a repeated minimally painful stimulus). This project will test the hypothesis that these
delayed changes in autonomic nervous system function are secondary to a rise in ACTH that
occurs in response to stress.

Primary Aim. Infusion of ACTH (cosyntropin) will lead the next day to decreased cardiovagal
baroreflex sensitivity in healthy subjects.

Inclusion Criteria:

Subjects must be currently healthy, BMI 18-32 kg/m2, and not be on any medications.

This study will recruit men and women. Due to concerns about estrogen's effects on hormone
levels and possible contributions of menstrual symptoms on pain sensing thresholds, we will
schedule the inpatient studies to avoid the early follicular phase in normally cycling
women.

Subjects must have normal laboratory values for:

1. Complete blood count

2. Serum creatinine, sodium, potassium, glucose, liver enzymes

3. Urinalysis

4. Urine pregnancy test (if female)

5. Normal ECG

Exclusion Criteria:

We will exclude individuals with:

- Systolic blood pressure > 140 or < 90 mm Hg

- Diastolic blood pressure > 90 mm Hg

- Creatinine clearance ≤ 60 mL/min, as calculated by MDRD formula

- Known DM, CHF, CAD, PVD, CVA, MI, asthma

- Known or history of Cushing's disease or adrenal insufficiency

- Known neurologic disease

- Known psychiatric disease

- Steroid use (oral or inhaled, local or systemic injections, within the past 6 months)

- Significant concomitant medical illnesses

- Current excessive alcohol (>10oz ethanol/week)

- Current use of recreational drugs

- Current smokers

- Current pregnancy

- Chronic use of non-steroidal anti-inflammatory or narcotic medications

- Evidence of ischemia or heart block on screening electrocardiogram (greater than type
I-second degree heart block, left bundle branch block, or ST-T wave changes in 2 or
more contiguous leads)

- Subjects taking any prescription medications (other than oral birth control pills) or
herbal medications will be excluded.