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- Title
Increased myocardial contractility and enhanced exercise function in transgenic mice overexpressing either adenylyl cyclase 5 or 8.
- Authors
Esposito, Giovanni; Perrino, Cinzia; Ozaki, Tohru; Takaoka, Hideyuki; Defer, Nicole; Petretta, Maria; Angelis, Maria; Mao, Lan; Hanoune, Jacques; Rockman, Howard; Chiariello, Massimo
- Abstract
ß-adrenergic receptors (ßARs) are powerful regu- lators of cardiac function in vivo, activating heterotrimeric G proteins and the effector molecule adenylyl cyclase (AC). Interestingly, cardiac-specific overexpression of different AC isoforms leads to variable changes in cardiac function. Whether AC overexpression affects intrinsic cardiac contractility in an isoform-specific fashion determining a change in exercise capacity is currently unknown. To address this issue, we performed load-independent measurements of cardiac systolic and diastolic function by pressure–volume (PV) loop analysis in intact wild-type mice (WT) and transgenic mice overexpressing the AC isoforms 5 or 8. Here we show that cardiac overexpression of either AC5 or AC8 transgenic mice determined an increase in intrinsic cardiac contractility. Interestingly, AC8 transgenic mice displayed a significantly greater increase in cardiac contractility and improved active phase of relaxation. Despite these differences detected by PV loop analysis, both AC5 and AC8 mice showed a marked increase in exercise capacity on treadmill testing. Our results demonstrate that load-independent measurements of cardiac function are needed to compare different groups of genetically-modified mouse models and to detect subtle AC isoform-specific changes in cardiac performance.
- Subjects
CARDIAC contraction; EXERCISE; ADENYLATE cyclase; BETA adrenoceptors; HEART function tests
- Publication
Basic Research in Cardiology, 2008, Vol 103, Issue 1, p22
- ISSN
0300-8428
- Publication type
Article
- DOI
10.1007/s00395-007-0688-6