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There is increasing evidence that inhibition of tissue angiotensin converting enzyme (ACE) is important for the pharmacokinetics and pharmacodynamic effects of ACE inhibitors. Radioligand inhibitor binding methods using 125I-351A and either tissue homogenates or in vitro autoradiography have allowed in vitro and ex vivo quantitation of tissue ACE inhibition by a variety of ACE inhibitors. The rank order of potency against plasma as well as lung, kidney, and cardiac homogenates was quinaprilat = benazeprilat greater than perindoprilat greater than lisinopril greater than enalaprilat greater than fosinoprilat. The highest concentration of ACE in the heart was found in the cardiac valves followed by the right and left atria, then the right and left ventricles. Ex vivo studies showed that after oral administration of quinapril, ACE was inhibited dose-dependently in the lung, kidney, aorta and heart for more than 24h. Tissue bioavailability of the inhibitor is also an important determinant of tissue ACE inhibition. Perindopril crossed the blood-brain barrier and inhibited brain ACE at high doses, but after equivalent doses of quinapril no brain ACE inhibition could be demonstrated. These results suggest that it may be possible to design ACE inhibitors to have specific effects on ACE in different tissues.
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