Endogenous Renin-Angiotensin-Aldosterone System and Glucose Metabolism

In aim 1 subjects are randomized to cross over between an 8 day high salt and 8 day low salt
diet and assessments are made.

In aim 2, subjects are randomized to a 2x2 cross over study with an 8 day low salt diet and
either eplerenone 50mg or amlodipine 5mg.

Inclusion Criteria:

1. Ambulatory subjects, 18 to 70 years of age, inclusive

2. For female subjects, the following conditions must be met:

1. postmenopausal status for at least 1 year, or

2. status-post surgical sterilization, or

3. if of childbearing potential, utilization of adequate birth control and
willingness to undergo urine beta-hcg testing prior to drug treatment and on
every study day.

3. Metabolic Syndrome as defined by the presence of > 3 of the following:

1. Systolic Blood Pressure > 130 mm Hg OR Diastolic Blood Pressure > 85 mm Hg.

2. Glucose Intolerance (Fasting Plasma Glucose ≥ 100 mg/dL)

3. Increased triglyceride level > 150mg/dL (1.7mmol/L)

4. Decreased levels of HDL cholesterol (For males, less than 40 mg/dL; For females,
less than 50 mg/dL)

5. Waist circumference (For males, greater than 40 inches; For females, greater than
35 inches)

Exclusion Criteria:

1. type 1 Diabetes

2. Type II Diabetes

3. Impaired renal function

4. Prior allergies to medications used in the study protocol

5. Screening plasma potassium >5.5 mmol/L or sodium <135 mmol/L

6. Cardiovascular disease

7. Use of hormone replacement therapy

8. Breast-feeding

9. Treatment with anticoagulants

10. History of serious neurologic disease

11. History or presence of immunological or hematological disorders

12. Diagnosis of asthma requiring use of inhaled beta agonist

13. Clinically significant gastrointestinal impairment

14. Impaired hepatic function

15. Hematocrit <35%

16. Any underlying or acute disease requiring regular medication which could possibly pose
a threat to the subject or make implementation of the protocol or interpretation of
the study results difficult, such as arthritis treated with non-steroidal
antiinflammatory drugs

17. Treatment with chronic systemic glucocorticoid therapy

18. Treatment with lithium salts

19. History of alcohol or drug abuse

20. Treatment with any investigational drug in the 1 month preceding

21. Mental conditions rendering the subject unable to understand the nature, scope and
possible consequences of the study

22. Inability to comply with the protocol, e.g., uncooperative attitude, inability to
return for follow-up visits, and unlikelihood of completing the study