Hypoglycemia and Autonomic Nervous System Function-B

This study involves three interventions, which are performed in random order. Each
intervention involves a 3-day inpatient visit. There is a space of 1-3 months between
interventions. The three interventions are: 1) placebo with a hyperinsulinemic euglycemic
clamp, 2) spironolactone with a hyperinsulinemic hypoglycemic clamp, or 3) placebo with a
hyperinsulinemic hypoglycemic clamp. Each 3-day inpatient visit includes the following. On
Day 1, autonomic testing is performed. Autonomic testing includes assessment of Baroreflex
Sensitivity (BRS). BRS is assessed using the Modified Oxford procedure, which involves
sequential administration of nitroprusside and phenylephrine while measuring heart rate and
beat to beat blood pressure with a finapress and assessing Muscle Sympathetic Nerve Activity
(MSNA). MSNA is measured using microelectrodes placed near the peroneal nerve. On Day 2,
hyperinsulinemic clamps are performed with pre-treatment with either placebo or
spironolactone. Modified Oxford Procedures are performed prior to and during each clamp on
Day 2. On Day 3, the autonomic testing performed on Day 1 is repeated..

Inclusion Criteria:

- Healthy volunteers

- Males and females age 18 to 55 years

Exclusion Criteria:

- Pregnancy

- Lactation

- Clinically evident coronary artery, cerebrovascular, or peripheral vascular disease,
or presence of systemic illness that might affect autonomic function. Such illnesses
include diabetes mellitus, congestive heart failure, hypertension, renal, pulmonary,
hepatic disease, anemia, malignancies, untreated thyroid disease, and alcoholism.

- Current major depressive illness

- In all subjects, any individuals on oral, injected, inhaled or topical corticosteroids
within the last year or oral contraceptives within the past 3 months will be excluded.

- Use of medications other than thyroxine

- Known hypersensitivity to nitroglycerin, nitroprusside and/or phenylephrine.

- Blood pressure > 140/90 mmHg

- Creatinine > 1.5 mg/dL

- Serum potassium >5.2 mmol/L

- Estimated GFR < 50 mL/min

- Use of Viagra, Cialis, and similar drugs within 72 hours of admission.