Single and combined therapy for systemic hypertension with propranolol, hydralazine and hydrochlorothiazide: Hemodynamic and neuroendocrine mechanisms of action

• Published in: The American journal of cardiology Vol. 56; no. 4; pp. 315 - 320
• Main Authors: Mulvihill-Wilson, Julia, Gaffney, F.Andrew, Neal, William W., Graham, Robert M., Pettinger, William A., Blomqvist, C.Gunnar
• Format: Journal Article
• Language: English
• Published: New York, NY Elsevier Inc 01.08.1985; Elsevier
• Subjects: Adult; Antihypertensive agents; Biological and medical sciences; Cardiovascular system; Drug Therapy, Combination; Exercise Test; Female; Hemodynamics - drug effects; Humans; Hydralazine - pharmacology; Hydrochlorothiazide - pharmacology; Hypertension - drug therapy; Hypertension - physiopathology; Hypotension, Orthostatic - physiopathology; Male; Medical sciences; Middle Aged; Neurosecretory Systems - drug effects; Pharmacology. Drug treatments; Posture; Propranolol - pharmacology; Space life sciences; Vascular Resistance - drug effects; Diuretic; Hypertension; Drug combination; Chemotherapy; Vasodilator agent; Antihypertensive agent; Cardiovascular disease; Hemodynamics; Mechanism of action; Beta blocking agent
• ISSN: 0002-9149; 1879-1913
• DOI: 10.1016/0002-9149(85)90856-2

The antihypertensive mechanisms of single and combined therapy with a β-adrenergic antagonist (propranolol) and a vasodilator (hydralazine) were investigated in 9 patients with moderately severe hypertension, who were receiving maintenance diuretic (hydrochlorothiazide) treatment. Hemodynamic and neuroendocrine responses were determined at rest and during lower body negative pressure, and dynamic and static exercise stress after the chronic administration of propranolol and hydralazine, given alone or in combination. All 3 drug regimens, each administered for at least 10 weeks, reduced blood pressure (p <0.05) compared with diuretic-only therapy in patients at rest, in both the supine and standing position, and during lower body negative pressure and dynamic exercise. There was a significant additive antihypertensive effect when propranolol and hydralazine were combined. Only combination therapy effectively lowered pressure during static exercise. The regimens produced divergent effects on the supine cardiac output: a decrease with propranolol (p <0.05), no change with combination therapy and an increase with hydralazine (p <0.05). Both hydralazine and combination therapy significantly reduced supine total peripheral resistance (p <0.05), whereas propranolol produced no change. All 3 drug treatments significantly reduced total peripheral resistance during upright rest and dynamic exercise (p <0.05), without changing cardiac output or maximal exercise capacity. During exercise, cardiac output was maintained in patients treated with propranolol and in those treated with combined therapy by increases in stroke volume (p <0.05). Despite lower blood pressure, plasma norepinephrine concentrations were unchanged, although plasma renin activity decreased with propranolol and combination therapy. These findings indicate that propranolol's predominant antihypertensive mechanism in patients treated with diuretic drugs is a reduction in cardiac output in the supine position and a reduction in total peripheral resistance in the upright position. The propranolol-hydralazine combination effectively lowered blood pressure during static exercise without affecting exercise capacity or orthostatic tolerance.