ANGIOTENSIN CONVERTING ENZYME BINDING-SITES IN HUMAN HEART AND LUNG - COMPARISON WITH RAT-TISSUES

1 Angiotensin converting enzyme (ACE), a dipeptidyl carboxypeptidase which catalyzes the final activation step in the formation of angiotensin II, was identified by radioligand studies in rat heart and lung. In this work we identified ACE binding sites in human left ventricle and lung by radioligand binding using the ACE inhibitor [H-3]-ramiprilat, and compared its binding characteristics in human and rat tissues. 2 Binding of [H-3]-ramiprilat in all tissues tested was saturable, temperature and zinc-dependent, and inhibited by EDTA. In human left ventricle homogenate we found a density of binding sites of 121 +/- 15 fmol mg-1 protein (n = 4) with an affinity (K(d)) of 850 +/- 55 pm, whereas in rat left ventricle the same values were 23 +/- 4 fmol mg-1 protein and 315 +/- 30 pm, (n = 4), respectively. 3 [H-3]-ramiprilat binding to rat (n = 4) and human lung (n = 4) showed a binding site density of 2132 +/- 155 and 1085 +/- 51 fmol mg-1 protein respectively with an affinity of 639 +/- 54 and 325 +/- 22 pM. The lung: heart ratio of ACE binding site density was about 9:1 in man and 100:1 in rat. 4 The binding affinities of 13 ACE inhibitors were evaluated on human heart and lung: the drugs tested showed a wide range of affinities for the ACE binding sites in both tissues, and the affinity for lung was significantly greater than for heart for most of the drugs. 5 The greater potency of some ACE inhibitors in displacing [H-3]-ramiprilat in human lung compared with the heart indicates differences between ACE binding sites in these tissues and suggests the possibility of a selective organ-targeted therapeutic approach.