Hypoglycemia and the Mineralocorticoid Receptor

The effect of ongoing hypoglycemia on cardiovascular autonomic function is unclear and the
focus of this protocol. In our preliminary studies, the investigators demonstrated that
baroreflex sensitivity is impaired during hypoglycemia in healthy individuals. Treatment with
eplerenone (200mg total administered in two doses in the 15 hours prior to the hypoglycemic
clamp) prevented this impairment.

The study is based on the overarching hypothesis that hypoglycemia leads to increases in
aldosterone/mineralocorticoid receptor (MR) activity and increased cardiovascular injury.

This study will address the following Specific Aims:

To test the hypothesis that MR blockade will reduce the adverse effects of hypoglycemia on
inflammation and on autonomic control of cardiovascular function.

The investigators will determine the effects of hypoglycemia (50 mg/dl for 2.0 hours) on the
blood inflammatory factor interleukin-6 levels, and on cardiovascular autonomic function
(baroreflex sensitivity) in each subject under two conditions - pretreatment with MR blockade
(eplerenone) and pretreatment with placebo.

Inclusion Criteria:

- Healthy volunteers

- Males and females age 18 to 40 years

Exclusion Criteria:

- Pregnancy

- Lactation

- Menopause

- Any medical condition other than treated hypothyroidism.

- Alcoholism

- Active tobacco use

- 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 physiological thyroxine replacement

- Serum potassium >5.0 mmol/L

- Estimated glomerular filtration rate < 60 mL/min