Abstract
The authors recently reported the development of a new method for measuring angiotensin converting enzyme (ACE) by means of highly sensitive angiotensin II RIA technique. We have carried out a comparative study of the pharmacological properties of captopril and MK-422, two ACE inhibitors recently developed as new antihypertensive agents. In this study, in vivo and in vitro animal experiments were performed using the Gottingen Mini-pig (Mini-pig G) animal model of the human disease. In the in vivo experimental system, each drug was administered by intravenous injection at a dose of 1 mg/kg, and a slight difference was found in the time-course of the per cent inhibition of ACE in the blood. In the in vitro system (cultured aortic endothelial cells), the ACE inhibitory activities of the two drugs were compared in terms of the 50%-inhibition point on the dose response curve, and it was found that MK-422 was about 100 times more potent than captopril. These results indicate that our newly-developed experimental system can be useful in the establishment of the clinical dose of vasoactive drugs that act on the renin-angiotensin system.
