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Differential Effects of Diuresis and Beta‐Adrenoreceptor Blockade During Angiotensin‐Converting Enzyme Inhibition in Patients with Severe Hypertension
Author(s) -
DRAYER JAN I. M.,
WEBER MICHAEL A.,
LIPSON JODI L.,
MEGAFFIN BERNARD B.
Publication year - 1982
Publication title -
the journal of clinical pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.92
H-Index - 116
eISSN - 1552-4604
pISSN - 0091-2700
DOI - 10.1002/j.1552-4604.1982.tb02160.x
Subject(s) - captopril , hydrochlorothiazide , propranolol , blood pressure , hydralazine , diuretic , supine position , medicine , angiotensin converting enzyme , heart rate , endocrinology , beta blocker , pindolol , heart failure
The orally administered blocker of angiotensin‐converting enzyme, captopril, was given to 16 patients with moderate to severe hypertension in whom blood pressure could not adequately be controlled by combination treatment with a vasodilator (hydralazine 200 mg daily), a beta‐blocker (propranolol 320 mg daily), and a diuretic (hydrochlorothiazide 100 mg daily). Captopril (450 mg daily) alone maintained blood pressure at the same levels as during previous administration of the combination, although in the absence of the diuretic and the beta‐blocker there were increases in body weight of 1.8 ± 0.5 (S.E.) kg ( P <0.01) and in supine heart rate of 10 ± 4 beats/min ( P < 0.01). After hydrochlorothiazide (100 mg daily) was added to the captopril, the supine mean blood pressure of 122 ± 5 mm Hg was significantly lower than during captopril alone (134 ± 4 mm Hg, P <0.01). Heart rate increased from 79 ± 3 to 90 ± 5 beats/min ( P <0.05). In 13 of the 16 patients, in whom supine diastolic blood pressure still remained higher than 90 mm Hg, the addition of propranolol (120–360 mg daily) to the captopril‐hydrochlorothiazide combination decreased heart rate from 88 ± 5 to 65 ± 3 beats/min ( P < 0.01), but failed to produce a further blood pressure decrement. However, the supine mean blood pressure during the captopril‐hydrochlorothiazide‐propranolol combination of 120 ± 5 mm Hg was significantly lower ( P < 0.05) than that (132 ± 6 mm Hg) during the hydralazine‐hydrochlorothiazide‐propranolol combination. Despite similar diuretic doses in the two regimens, serum potassium concentration was significantly higher during treatment with the captopril combination (4.3 ± 0.2 vs. 3.6 ± 0.2 mEq/l., P <0.01). It seems likely that converting enzyme inhibition by captopril increases the sensitivity of the blood pressure response to diuretic therapy, in part by blocking the countervailing effects of the reactive rise in renin release that is stimulated by sodium depletion. In these renin‐blocked patients, however, addition of propranolol does not appear to produce any further antihypertensive effect.