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Endocrine profile in the long-term phase of converting-enzyme inhibition
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1980
Year
HypertensionRenal InflammationCardiovascular PharmacologyPharmacotherapyBlood PressureMolecular PharmacologyEndocrine ProfileRenal PharmacologyEndocrine HypertensionEndocrine MechanismSodium HomeostasisAntihypertensive TherapyVascular PharmacologyDiuretic ResistancePlasma KininsEndocrinologyPharmacologyPotassium HomeostasisCardiovascular DiseasePhysiologyBlood Pressure ControlSodium RestrictionMetabolismMedicine
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 E2 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