Single and combined therapy for systemic hypertension with propranolol, hydralazine and hydrochlorothiazide: hemodynamic and neuroendocrine mechanisms of action.
The antihypertensive mechanisms of single and combined therapy with a beta-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 less than 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 less than 0.05), no change with combination therapy and an increase with hydralazine (p less than 0.05). Both hydralazine and combination therapy significantly reduced supine total peripheral resistance (p less than 0.05), whereas propranolol produced no change. All 3 drug treatments significantly reduced total peripheral resistance during upright rest and dynamic exercise (p less than 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 less than 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)
D000328:Adult; D004359:Drug Therapy, Combination; D005080:Exercise Test; D005260:Female; D006439:Hemodynamics / Q000187:drug effects*; D006801:Humans; D006830:Hydralazine / Q000494:pharmacology*; D006852:Hydrochlorothiazide / Q000494:pharmacology*; D006973:Hypertension / Q000188:drug therapy* / Q000503:physiopathology; D007024:Hypotension, Orthostatic / Q000503:physiopathology; D008297:Male; D008875:Middle Aged; D009490:Neurosecretory Systems / Q000187:drug effects*; D011187:Posture; D011433:Propranolol / Q000494:pharmacology*; D014655:Vascular Resistance / Q000187:drug effects
D006852:Hydrochlorothiazide; D006830:Hydralazine; D011433:Propranolol