The pharmacodynamic responses of hypertensive patients to quinapril therapy

Impaired baroreflex-induced release of noradrenaline during angiotensin converting enzyme (ACE) inhibition may interfere with orthostatic responses of blood pressure.

To compare blood pressure and heart rate responses of hypertensive patients to upright posture over a 12 h period before and after quinapril therapy.

Four weeks of placebo was given to all patients. If subject's sitting diastolic blood pressure was between 100 and 115 mmHg, patients received 2.5, 5, 10 or 20 mg quinapril bid for four more weeks in a double-blind randomized fashion.

Ambulatory hypertension clinic with admission to clinical investigation unit overnight for interventions.

Uncomplicated essential hypertensives of English or Irish ancestry. Twenty-five eligible patients completed the study while three withdrew early.

Supine and erect blood pressures and heart rates were recorded for each patient at 1 to 2 h intervals over a 12 h period following ingestion of placebo capsule and again after initial acute dose of quinapril the next day. Blood was sampled for quinapril and quinaprilat concentrations. Procedure was repeated after four weeks of quinapril therapy following morning dose of drug.

Orthostatic response of diastolic pressure was reduced while maintenance of systolic was impaired 1 to 4 h following an acute dose of quinapril. Orthostatic cardioacceleration was maintained. Responses were largely restored after four weeks of chronic therapy.

A possible initial impairment of baroreflex-mediated peripheral vasoconstriction by ACE inhibition may be offset by compensatory changes to vascular reactivity.