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Endocrine profile in the long‐term phase of converting‐enzyme inhibition
Author(s) -
Swartz Stephen L,
Williams Gordon H,
Hollenberg Norman K,
Crantz Frank R,
Moore Thomas J,
Levine Lawrence,
Sasahara Arthur A,
Dluhy Robert G
Publication year - 1980
Publication title -
clinical pharmacology and therapeutics
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.941
H-Index - 188
eISSN - 1532-6535
pISSN - 0009-9236
DOI - 10.1038/clpt.1980.194
Subject(s) - captopril , hydrochlorothiazide , plasma renin activity , endocrinology , medicine , blood pressure , diuretic , renin–angiotensin system , chemistry , angiotensin ii , pharmacology
Captopril is a potent antihypertensive whose mechanism of action may involve changes in several vasoactive hormonal systems (renin‐angiotensin, kallikrein‐kinin, prostaglandin). Since these potential mediators of the captopril hypotensive effect may vary with duration of therapy, we studied the changes in these vasoactive systems during the short‐ and long‐term phases of captropril treatment in 31 patients with essential hypertension, most of whom were treated for over 9 mo. We related the captopril blood pressure‐lowering effect to changes in these systems, and also determined whether sodium restriction and diuretic therapy had any modifying effect. During short‐term administration of captopril in the sodium‐restricted state, supine diastolic blood pressure (SDBP) fell 18 ± 2 mm Hg (p < 0.01), and was associated with decrements in angiotensin II (A II) (−9 ± 3 pg/ml) and increments in plasma kinins (1.0 ± 0.2 ng/ml) (p < 0.05). During long‐term administration of captopril and hydrochlorothiazide (HCTZ), the fall in blood pressure (−23 ± 2 mm Hg, p < 0.01) was sustained for at least 9 mo of therapy. Combined capotopril and HCTZ therapy results in a greater reduction in SDBP (−23 ± 2 mm Hg) than with captopril alone (−11 ± 2 mm Hg) (p < 0.01). In contrast to the immediate hormonal changes, during long‐term therapy plasma A II levels were slightly higher than control (11 ± 3 pg/ml) presumably because of a reactive increase in plasma renin activity, and plasma kinins continued to rise (2.6 ± 1.0 ng/ml, p < 0.01), while prostaglandin E 2 metabolites were also elevated (20 ± 8 pg/ml, p = 0.0083). Captopril is therefore a potent antihypertensive agent when used in combination with sodium restriction or a diuretic. During the short‐term phase of administration, the fall in blood pressure is associated with reduction in A II generation and an increase in kinin levels. In the long‐term phase, however, A II seems to play a smaller role, if any, while kinins and potentially prostaglandins assume a more prominent role in mediating the captopril hypotensive effect. Clinical Pharmacology and Therapeutics (1980) 28, 499–508; doi: 10.1038/clpt.1980.194