Angiotensin converting enzyme is the main contributor to angiotensin I-II conversion in the interstitium of the isolated perfused rat heart

Objectives Recent studies in homogenized hearts suggest that chymase rather than angiotensin converting enzyme (ACE) is responsible for cardiac angiot ensin I to angiotensin II conversion. We investigated in intact rat hearts whether (i) enzymes other than ACE contribute to angiotensin I to angiotens in II conversion and (ii) the localization (endothelial/extra-endothelial) of converting enzymes. Design and Methods We used a modified version of the rat Langendorff heart, allowing separate collection of coronary effluent and interstitial fluid. Hearts were perfused with angiotensin I (arterial concentration 5-10 pmol/m l) under control conditions, in the presence of captopril (1 mu mol/l) or a fter endothelium removal with 0.2% triton X-100, Endothelium removal was ve rified as the absence of a coronary vasodilator response to 10 nmol bradyki nin. Angiotensin I and angiotensin II were measured in coronary effluent an d interstitial fluid with sensitive radioimmunoassays. Results In control hearts, 45% of arterial angiotensin I was metabolized du ring coronary passage, partly through conversion to angiotensin II. At stea dy-state, the angiotensin I concentration in interstitial fluid was three t o four-fold lower than in coronary effluent, while the angiotensin II conce ntrations in both fluids were similar. Captopril and endothelium removal di d not affect coronary angiotensin I extraction, but increased the interstit ial fluid levels of angiotensin I two- and three-fold, respectively, thereb y demonstrating that metabolism (by ACE) as well as the physical presence o f the endothelium normally prevent arterial angiotensin I from reaching sim ilar levels in coronary effluent and interstitial fluid. Captopril, but not endothelium removal, greatly reduced the angiotensin II levels in coronary effluent and interstitial fluid, With the ACE inhibitor, the angiotensin I I/I ratios in coronary effluent and interstitial fluid were 83 and 93% lowe r, while after endothelium removal, the ratios were 33 and 71% lower. Conclusions In the intact rat heart, ACE is the main contributor to angiote nsin I to angiotensin II conversion, both in the coronary vascular bed and the interstitium. Cardiac ACE is not limited to the coronary vascular endot helium. J Hypertens 19:959-965 (C) 2001 Lippincott Williams & Wilkins.