ANGIOTENSIN CONVERTING ENZYME IN THE RAT HEART: STUDIES OF ITS INHIBITION <i>IN VITRO</i> AND <i>EX VIVO</i>

Abstract

1. The pharmacokinetics of angiotensin converting enzyme (ACE) inhibition in rat heart and lung was evaluated in vitro and ex vivo. 2. Radioinhibitor [125I]-351A binding displacement was used to assess the relative potency of six ACE-inhibitors (CI906, CGS14831, S9780, 351A, MK521, SQ27519) in rat heart and lung homogenates, and estimate equilibrium association constant (Ka). 3. Following oral administration of 0.3 mg/kg of Quinapril (CI928) specific binding of [125I]-351A to ACE was measured in rat heart. 4. Ka for binding to ACE of each inhibitor was significantly higher in right and left atrium than in lung (P less than 0.05) or the right and left ventricle (P less than 0.005). These differences did not affect the degree or time course of inhibition in vivo in the rat myocardial ACE following Quinapril treatment. 5. Rank order of potency of the ACE inhibitors tested was CI906 = CGS14831 greater than S9780 greater than 351A greater than MK521 greater than SQ27519