PERINDOPRIL CHRONICALLY INHIBITS ANGIOTENSIN-CONVERTING ENZYME IN BOTH THE ENDOTHELIUM AND ADVENTITIA OF THE INTERNAL MAMMARY ARTERY IN PATIENTS WITH ISCHEMIC-HEART-DISEASE

Background ACE inhibitors are widely used in treating hypertension and heart failure, but the sites and mechanisms of ACE inhibition in huma n blood vessels ore not understood. The present study was undertaken t o assess the sites and extent of in vivo inhibition of ACE by long-ter m perindopril treatment in different lavers of the internal mammary ar tery in patients with ischemic heart disease. Methods and Results Sixt een patients with ischemic heart disease were treated either with peri ndopril (4 mg/d PO) for up to 36 days before surgery (n=9) or without the inhibitor as control subjects (n=7. The segments of the internal m ammary artery were collected for measurement of vascular fret and tota l ACE by quantitative in vitro autoradiography with I-125-35lA binding . The patients treated with perindopril had lower plasma ACE (P<.001) and plasma angiotensin (Ang) II-to-Ang I ratio (P<.05). In the interna l mammary artery, free ACE was similarly inhibited by perindopril in t he endothelium (P<.05) and adventitia (P<.05), and the fret ACE-to-tot al ACE ratio, an index of ACE inhibition, was markedly decreased by pe rindopril in parallel in the endothelium (P<.001) and adventitia (P<.0 01). Moreover. plasma ACE correlated highly with vascular ACE in the e ndothelium (r=.85, P<.001) or adventitia (r=.78, P<.001), and mean art erial pressure correlated significantly with free ACE in the endotheli um (r=.52, P<.05 or adventitia (r=.53. P<.05) and with the plasma Ang II-to-Ang I ratio (r=.53, P<.05). Light microscopic autoradiographs of I-125-351A binding revealed a marked inhibition of ACE by perindopril in both layers of the vascular wall. Conclusions The present study de monstrates that long-term administration of perindopril potently inhib its both endothelial and adventitial ACE to a comparable degree in the human internal mammary artery. These results indicate that perindopri l effectively penetrates the vascular wall to inhibit ACE in the adven titial thus providing evidence that perindopril may be beneficial in i nhibiting both circulating Ang II and its local formation in the vascu lar wall.