Isolated circulatory response to intravenous administration of the ACE inhibitor enalaprilat.

Abstract

The isolated vascular effects of intravenous administration of the angiotensin converting enzyme (ACE) inhibitor enalaprilat were investigated. Thirty male patients undergoing cardiopulmonary bypass (CPB) were studied. According to a randomized sequence, 0.04 mg kg‐1 enalaprilat (low‐dose, n = 10), 0.08 mg kg‐1 (high‐dose, n = 10) enalaprilat or saline solution as placebo (control group, n = 10) was given as an i.v. bolus during CPB. Changes in mean arterial pressure (MAP) and venous reservoir (RV) of the extracorporeal circulation were studied as indices of arterial resistance and venous capacitance. Mean arterial blood pressure (MAP) and peripheral vascular resistance (SVR) were significantly more reduced in the high‐dose enalaprilat group (MAP: ‐36 mm Hg after 9 min; SVR: ‐836 dyn s cm‐5) than in the low‐dose group (MAP: ‐13 mm Hg after 10 min). Volume of the reservoir (RV) decreased in both enalaprilat treated groups indicating additional (dose‐dependent) venous pooling effects of the substance (low‐dose: ‐ 300 ml; high‐dose: ‐520 ml; control group: ‐100 ml). Skin capillary blood flow measured by laser Doppler flowmetry (LDF) increased after injection of 0.04 mg kg‐1 enalaprilat, whereas it decreased significantly when MAP fell markedly in patients treated with high‐dose enalaprilat. I.v. enalaprilat had dose‐dependent vasodilating properties in the arterial and venous vessel system indicating reduction in pre‐ and afterload. Microcirculation in both enalaprilat treated groups improved as long as reduction in blood pressure was not limited. 1994 The British Pharmacological Society