Impact of Aldosterone Receptor Blockade Compared With Thiazide Therapy on Sympathetic Nervous System Function in Geriatric Hypertension

Abstract

Aldosterone receptor blockade and thiazide therapy effectively lower blood pressure in geriatric hypertension. Their impact on sympathetic nervous system function has not been evaluated. In a double-blind, randomized study, 36 patients with stage 1 hypertension underwent 6 months of therapy with either aldosterone receptor blockade (spironolactone, n=19; 68±1 years) or hydrochlorothiazide (n=17; 68±2 years). Arterial blood pressure, [ 3 H]-norepinephrine (NE) kinetics (extravascular NE release rate), and α-adrenergic responsiveness (forearm vasoconstriction to graded intrabrachial artery NE infusions) were evaluated at baseline, after a 4-week antihypertensive medication withdrawal, and after spironolactone or hydrochlorothiazide treatment. Arterial blood pressure decreased significantly with both spironolactone (160±3 to 134±2 mm Hg; 77±2 to 68±2 mm Hg) and hydrochlorothiazide (161±4 to 145±4 mm Hg; 78±2 to 73±2 mm Hg) treatment. Sympathetic nervous system activity was significantly reduced after spironolactone (plasma NE: 378±40 to 335±20 pg/mL, P =0.04; [ 3 H]-NE release rate: 2.74±0.3 to 1.97±0.2 μg/min per meter squared, P =0.04) but not hydrochlorothiazide (plasma NE: 368±25 to 349±23 pg/mL, P =0.47; [ 3 H]-NE release rate: 2.63±0.4 to 2.11±0.2 mg/min per meter squared, P =0.21). α-Adrenergic responsiveness was unchanged with either drug treatment. These findings demonstrate a beneficial effect of aldosterone receptor blockade on reducing sympathetic nervous system activity and blood pressure in hypertensive older patients.