title: 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 alpha-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 microg/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). alpha-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.
authors.affiliation: Division of Geriatrics, Department of Internal Medicine, University of Utah, Salt Lake City, UT 84132, USA. walter.wray@hsc.utah.edu
authors.forename: D Walter
authors.initials: DW
authors.lastname: Wray
authors.forename: Mark A
authors.initials: MA
authors.lastname: Supiano
mesh_terms: D000368:Aged; D000450:Aldosterone / Q000097:blood; D001794:Blood Pressure / Q000187:drug effects*; D001823:Body Composition; D002395:Catecholamines / Q000097:blood; D004232:Diuretics / Q000627:therapeutic use; D005260:Female; D006339:Heart Rate / Q000187:drug effects; D006801:Humans; D006852:Hydrochlorothiazide / Q000627:therapeutic use*; D006973:Hypertension / Q000097:blood / Q000188:drug therapy / Q000503:physiopathology*; D008075:Lipoproteins, HDL / Q000097:blood; D008077:Lipoproteins, LDL / Q000097:blood; D008297:Male; D008875:Middle Aged; D000451:Mineralocorticoid Receptor Antagonists / Q000627:therapeutic use*; D009638:Norepinephrine / Q000097:blood; D018579:Patient Selection; D013148:Spironolactone / Q000627:therapeutic use*; D013564:Sympathetic Nervous System / Q000187:drug effects / Q000503:physiopathology*
chemical_list: D002395:Catecholamines; D004232:Diuretics; D008075:Lipoproteins, HDL; D008077:Lipoproteins, LDL; D000451:Mineralocorticoid Receptor Antagonists; D006852:Hydrochlorothiazide; D013148:Spironolactone; D000450:Aldosterone; D009638:Norepinephrine