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

• Ambulatory subjects, 18 to 70 years of age, inclusive
• For female subjects, the following conditions must be met:

• postmenopausal status for at least 1 year, or
• status-post surgical sterilization, or
• 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.
• Metabolic Syndrome as defined by the presence of > 3 of the following:

• Systolic Blood Pressure > 130 mm Hg OR Diastolic Blood Pressure > 85 mm Hg.
• Glucose Intolerance (Fasting Plasma Glucose ≥ 100 mg/dL)
• Increased triglyceride level > 150mg/dL (1.7mmol/L)
• Decreased levels of HDL cholesterol (For males, less than 40 mg/dL; For females, less than 50 mg/dL)
• Waist circumference (For males, greater than 40 inches; For females, greater than 35 inches)

Exclusion criteria

• type 1 Diabetes
• Type II Diabetes
• Impaired renal function
• Prior allergies to medications used in the study protocol
• Screening plasma potassium >5.5 mmol/L or sodium <135 mmol/L
• Cardiovascular disease
• Use of hormone replacement therapy
• Breast-feeding
• Treatment with anticoagulants
• History of serious neurologic disease
• History or presence of immunological or hematological disorders
• Diagnosis of asthma requiring use of inhaled beta agonist
• Clinically significant gastrointestinal impairment
• Impaired hepatic function
• Hematocrit <35%
• 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
• Treatment with chronic systemic glucocorticoid therapy
• Treatment with lithium salts
• History of alcohol or drug abuse
• Treatment with any investigational drug in the 1 month preceding
• Mental conditions rendering the subject unable to understand the nature, scope and possible consequences of the study
• Inability to comply with the protocol, e.g., uncooperative attitude, inability to return for follow-up visits, and unlikelihood of completing the study