Several large clinical trials of angiotensin converting enzyme (ACE) inhibitors have demonstrated the critical role of the renin angiotensin system (RAS) in the pathogenesis of heart failure. These trials also indicate an unexplained heterogeneity in response to ACE-inhibitor therapy. The general hypothesis to be tested in this application is that there is variation in ACE activity in the falling human heart. An in vivo protocol using intracoronary 123I-Ang I will be used to study Ang II formation in the intact failing human heart.

Agency
National Institute of Health (NIH)
Institute
National Heart, Lung, and Blood Institute (NHLBI)
Type
Clinical Investigator Award (CIA) (K08)
Project #
5K08HL003404-04
Application #
2750258
Study Section
Research Training Review Committee (RTR)
Project Start
1995-08-01
Project End
1998-08-02
Budget Start
1998-08-01
Budget End
1998-08-02
Support Year
4
Fiscal Year
1998
Total Cost
Indirect Cost
Name
University of Colorado Denver
Department
Internal Medicine/Medicine
Type
Schools of Medicine
DUNS #
065391526
City
Aurora
State
CO
Country
United States
Zip Code
80045
Zisman, Lawrence S; Keller, Rebecca S; Weaver, Barbara et al. (2003) Increased angiotensin-(1-7)-forming activity in failing human heart ventricles: evidence for upregulation of the angiotensin-converting enzyme Homologue ACE2. Circulation 108:1707-12
Bohlmeyer, Teresa; Ferdensi, Anthony; Bristow, Michael R et al. (2003) Selective activation of N-acyl-D-glucosamine 2-epimerase expression in failing human heart ventricular myocytes. J Card Fail 9:59-68
Zisman, Lawrence S; Meixell, Glenn E; Bristow, Michael R et al. (2003) Angiotensin-(1-7) formation in the intact human heart: in vivo dependence on angiotensin II as substrate. Circulation 108:1679-81
Asano, Koji; Bohlmeyer, Teresa J; Westcott, Jay Y et al. (2002) Altered expression of endothelin receptors in failing human left ventricles. J Mol Cell Cardiol 34:833-46
Zisman, L S; Asano, K; Dutcher, D L et al. (1998) Differential regulation of cardiac angiotensin converting enzyme binding sites and AT1 receptor density in the failing human heart. Circulation 98:1735-41