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Beneficial Effects of Combined Benazepril-Amlodipine on Cardiac Nitric Oxide, cGMP, and TNF- Production After Cardiac Ischemia

Siragy, Helmy M. MD*; Xue, Chun MD*; Webb, Randy L. PhD

Journal of Cardiovascular Pharmacology:
doi: 10.1097/01.fjc.0000211750.01326.b3
Original Articles

The aim of this study was to determine if myocardial inflammation is increased after myocardial ischemia and whether angiotensin-converting enzyme inhibitors, calcium channel blockers, or diuretics decrease mediators of inflammation in rats with induced myocardial ischemia. Changes in cardiac interstitial fluid (CIF) levels of nitric oxide metabolites (NOX), cyclic guanosine 3′,5′-monophosphate (cGMP), angiotensin II (Ang II), and tumor necrosis factor-α (TNF-α) were monitored with/without oral administration of benazepril, amlodipine, combined benazepril-amlodipine, or hydrochlorothiazide. Using a microdialysis technique, levels of several mediators of inflammation were measured after sham operation or 30-minute occlusion of the left anterior descending coronary artery. Compared with sham animals, levels of CIF NOX and cGMP were decreased in animals with ischemia (P<0.001). Benazepril or amlodipine significantly increased NOX levels (P<0.05 vs. untreated ischemia), but only benazepril significantly increased cGMP (P<0.05). Combined benazepril-amlodipine further increased CIF NOX and cGMP (P<0.001), compared with either drug alone. CIF Ang II and TNF-α in sham animals did not change significantly. In animals with ischemia, CIF Ang II and TNF-α increased progressively. Amlodipine alone, benazepril alone, or combined benazepril-amlodipine significantly reduced TNF-α (P<0.01 for monotherapies and P<0.001 for combination therapy). Hydrochlorothiazide did not cause significant changes in NOX, cGMP, or TNF-α. Combination benazepril-amlodipine may be beneficial for managing cardiac ischemia.

Author Information

*Department of Medicine, University of Virginia Health System, Charlottesville, VA

Novartis Institutes for Biomedical Research, East Hanover, NJ

Supported by Novartis Pharmaceuticals Corporation, East Hanover, NJ.

Reprints: Helmy M. Siragy, MD, Professor of Internal Medicine, Department of Internal Medicine, University of Virginia Health Science Center, 450 Ray C. Hunt Drive, Charlottesville, VA 22903 (e-mail:

Received for publication January 25, 2006; accepted March 17, 2006

© 2006 Lippincott Williams & Wilkins, Inc.