Moexipril and quinapril inhibition of tissue angiotensin-converting enzyme activity in the rat: evidence for direct effects in heart, lung and kidney and stimulation of prostacyclin generation.

The activation of angiotensin converting enzyme (ACE) may contribute to the development of vascular and myocardial structural changes. The level of ACE is stable in human plasma, and only limited data are available on its regulation at the tissue level. The aim of this study was to characterize the effects of two ACE inhibitors, moexipril and quinapril on tissue ACE activity. Adult male rats were treated intragastrically once daily for 6 days either with 2 mg/kg moexipril or quinapril. After single treatment, moexipril and quinapril effectively inhibited ACE activity in plasma and slightly in heart and aorta, whereas after 6 days of treatment they inhibited ACE activity in plasma (87% and 94%, respectively), lung (92% and 93%), myocardium (26% and 23%), kidney (21% and 20%), and aorta (39% and 40%), but not in skeletal muscle. Interestingly, the two ACE-inhibitors also induced a significant increase in cardiac homogenates of 6-keto-PGF1alpha levels, an important index of PGI2 generation. To test whether the reduced effects of ACE inhibitors in heart and kidney were caused by a limited availability of the drugs, 100 microl of lung, heart and kidney homogenates from control rats were incubated in vitro with moexipril and quinapril immediately before assay. Both drugs were more effective in lung than heart and kidney homogenates, with inhibition values superimposable to those obtained in vivo. These results clearly indicate that inhibition of tissue ACE activity does not depend primarily on the availability of ACE inhibitors in each organ.