An Angiotensin Converting-Enzyme Inhibitor to Identify and Treat Vasoconstrictor and Volume Factors in Hypertensive Patients

The antihypertensive action of nonapeptide competitive inhibitor of angiotensin-1-converting enzyme was evaluated in 13 hypertensive patients. In 12 a single injection (1 to 4 mg per kilogram) induced an immediate antihypertensive effect that lasted, depending on dose, up to 16 hours. Mean diastolic pressures (±S.E.) fell from 126±3 to 101±4 mm Hg. Plasma renin increased and aldosterone fell. Five patients, whose mean diastolic pressure fell 26 mm Hg but not to normal, were then sodium depleted. A mean loss of 187 mEq lowered diastolic pressure only 2 mm Hg. However, readministration of the nonapeptide then lowered diastolic pressure by 36 mm Hg. This synergism suggests that compensatory angiotensin vasoconstriction is involved in diuretic ineffectiveness. Conversely, poor pressure responses to angiotensin blockade appear related to pre-existing hypervolemia, correctable by diuretics. Therefore, this drug can be used to quantify volume and vasoconstrictor factors in hypertension and to design therapy against the two. Its specificity, safety and capacity to reduce aldosterone suggest other uses in acute hypertensive situations. (N Engl J Med 291:817–821, 1974)