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

One year after study completion, de-identified subject demographic data and primary outcome data will be available by request.

One year after study completion

By request.

Baseline through 10 weeks