DUAL PATHWAY FOR ANGIOTENSIN-II FORMATION IN HUMAN INTERNAL MAMMARY ARTERIES

1 Angiotensin converting enzyme (ACE) is thought to be the main enzyme to convect antiotensin I to the vasoactive angiotensin II. Recently, in the human heart, it was found that the majority of angiotensin ZI f ormation was due to another enzyme, identified as human heart chymase. In the human vasculature however, the predominance of either ACE or n on-ACE conversion of angiotensin I remains unclear. 2 To study the eff ects of ACE- and chymase-inhibition on angiotensin II formation in hum an arteries, segments of internal mammary arteries were obtained from 37 patients who underwent coronary bypass surgery. 3 Organ bath experi ments showed that 100 mu M captopril inhibited slightly the response t o angiotensin. I (pD(2) from 7.09+/-0.11 - 6.79+/-0.10, P < 0.001), wh ile 100 mu M captopril nearly abolished the response to [pro(10)] angi otensin I, a selective substrate for ACE, and the maximum contraction was reduced from 83+/-19% - 23+/-17% of the control response (P = 0.01 ). A significant decrease of the pD(2) of angiotensin I similar to cap topril was observed in the presence of 50 mu M chymostatin (pD(2) from 7.36+/-0.13-6.99+/-0.15, P<0.039), without influencing the maximum re sponse. In the presence of both inhibitors, effects were much more pro nounced than either inhibitor alone, and a 300 times higher dose was n eeded to yield a significant contraction response to angiotensin I. 4 These results indicate the presence of an ACE and a non-ACE angiontens in IT forming pathway in human internal mammary arteries.