Hypoglycemia and Autonomic Nervous System Function-B

Hypoglycemia and Autonomic Nervous System Function

This study tests the hypothesis that, compared to prior normal blood sugar, prior low blood sugar impairs cardiovascular autonomic function. The proposed studies will also test the hypothesis that the effects of prior low blood sugar on cardiovascular autonomic function are blocked by administration of a mineralocorticoid receptor antagonist.

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.