Increased angiotensin converting enzyme and chymase-like activity in cardiac tissue of dogs with chronic mitral regurgitation. Dell'italia, Louis J., Qing C. Meng, Eduardo Balcells, Ingrid M. Straeter-Knowlen, Gerald H. Hankes, Ray Dillon, R. Earl Cartee, Roger Orr, Sanford P. Bishop, Suzanne Oparil, Terry S. Elton. Birmingham Veteran Affairs Medical Center, University of Alabama at Birmingham, Department of Medicine, Division of Cardiology, University Station, Birmingham, Alabama 35294 and Auburn University College of Veterinary Medicine, Auburn, Alabama 36849-5525.
APStracts 2:0354H, 1995.
The current study was designed to test the hypothesis that intracardiac ACE activity, chymase-like activity, and angiotensin (ANG) peptide levels are increased and are positively related to wall stress estimates in response to the chronic low pressure volume overload of mitral regurgitation produced by percutaneous chordal rupture in the dog. Chronic mitral regurgitation (MR) resulted in an increase in left ventricular (LV) end-diastolic volume (59 +/- 11 [SD] to 103 +/- 32 ml, p &LT 0.001), LV mass (96 +/- 17 to 114 +/- 23 grams, p &LT0.001), and a decrease in the LV mass/end-diastolic volume ratio (1.64 + 0.22 to 1.16 + 0.23 gm/ml, p &LT 0.001) measured by magnetic resonance imaging. In-vitro studies of heart tissue extracts demonstrated that the majority of ANG II-forming activity was from chymase-like activity rather than from ACE activity in 5 normal (83.5 + 7.5% vs. 6.04 + 5.2% ) and 7 MR hearts (86 + 3.9% vs. 2.6 + 1.7%). ACE activity (1.22 +/- 0.22 vs. 3.55 +/- 0.62 mUnits/gm, p &LT 0.05) and chymase-like activity (9.42 +/- 4.64 vs. 20.60 + 8.41 nmol/gm/min, p &LT 0.05) were increased in MR compared to normal hearts. ACE activity correlated with the LV mass/volume ratio (r = -0.93, p &LT 0.001) and LV diastolic wall stress (r = 0.71, p &LT 0.05); however, chymase-like activity did not correlate with any hemodynamic parameter. ANG II levels were significantly higher in the midwall of the left ventricle in MR hearts than in normal controls (85 + 39 vs. 27 + 16 pg/gm, p &LT 0.01). Our results demonstrate a positive correlation between LV diastolic wall stress and increased ACE activity with increased ANG II stores, suggesting that mechanical wall stress activated intracardiac ACE. Although chymase accounted for most ANG II formation in-vitro in extracts of both normal and MR dog hearts, the significance of this enzyme in-vivo remains unclear. 

Received 10 February 1995; accepted in final form 7 June 1995.
APS Manuscript Number H125-5.
Article publication pending Am. J. Physiol. (Heart Circ. Physiology).
ISSN 1080-4757 Copyright 1995 The American Physiological Society.
Published in APStracts on 24 August 1995.