Mechanisms of Refractory Hypertension (Reserpine)

Mechanisms of Refractory Hypertension (Reserpine)

The study is deigned to determine if refractory hypertension is attributable to heightened sympathetic tone by quantifying the antihypertensive benefit of reserpine, a sympatholytic agent, in patients failing other classes of antihypertensive agents.

Patients with refractory hypertension, defined as uncontrolled office blood pressure despite use of 5 or more antihypertensive agents, including a thiazide diuretic and spironolactone. After withdrawal from other centrally-acting agents if needed, enrolled patients will be randomized to open-label reserpine 0.1 mg daily for 4 weeks. Twenty-four hour ambulatory blood pressure monitoring will be done at baseline, after the initial 4-week treatment period. All other antihypertensive medications will remain unchanged during the 4-week treatment period. The primary endpoint will be change in 24-hr ambulatory systolic blood pressure.

Inclusion Criteria:

- adult with refractory hypertension defined as uncontrolled office blood pressure with use of 5 or more hypertensive agents, including a thiazide diuretic and spironolactone

Exclusion Criteria:

• congestive heart failure (EF 40%)
• chronic kidney disease (GFR <40 ml/min/1.73 mm)
• stroke and/or myocardial infarction or acute CHF exacerbation within last 3 months
• ongoing depression
• active peptic ulcer disease
• bradycardia <50 beats per minute
• 2nd or 3rd degree heart block
• known intolerance of reserpine
• use of digoxin or tricycle antidepressants