Mechanism of Diastolic Stiffening of the Failing Myocardium and Its Prevention by Angiotensin Receptor and Calcium Channel Blockers

• DOI: 10.1097/fjc.0b013e3181ab371d
• Publication Date: 2009-07-15T07:31:32Z
• Authors: Xian Wu Cheng; Kenji Okumura; Masafumi Kuzuya; Zhehu Jin; Kohzo Nagata; Koji Obata; Aiko Inoue; Akihiro Hirashiki; Kyosuke Takeshita; Kazumasa Unno; Ken Harada; Guo-Ping Shi; Mitsuhiro Yokota; Toyoaki Murohara
• Keywords: Stiffening

Objective: To investigate the mechanism responsible for increased cardiac stiffness associated with hypertensive heart failure in Dahl salt-sensitive (DS) rats and effects of treatment combination a calcium channel blocker [azelnidipine (AZE)] angiotensin II type 1 receptor [olmesartan (OLM)]. Methods: DS fed high-salt diet from 7 weeks age were treated (or not) 12 to 19 vasodilator hydralazine, OLM plus AZE, or reduced nicotinamide adenine dinucleotide phosphate (NADPH) oxidase inhibitor apocynin. Rats low-salt served as controls. Results: Treatment AZE attenuated changes expression collagen isoforms decrease ratio elastin left ventricle prevented increase myocardial diastolic dysfunction manner independent hypotensive effect these drugs. Such also inhibited activation elastolytic proteases (including cathepsins S K metalloproteinases-2, -9, -12), NADPH oxidase-dependent superoxide production, inflammatory failing myocardium. All mimicked by Conclusions: The isoform myocardium likely account this model failure. Administration blockers drugs inhibiting activity induced oxidase.