OBJECTIVE: ss-adrenergic receptors (ssARs) are powerful regulators 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. METHODS: 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. RESULTS: 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. CONCLUSIONS: 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.

Increased myocardial contractility and enhanced exercise function in transgenic mice overexpressing either adenylyl cyclase 5 or 8 / Esposito, Giovanni; Perrino, Cinzia; Ozaki, T.; Takaoka, H.; Defer, N.; Petretta, M. P.; De Angelis, M. C.; Mao, L.; Hanoune, J.; Rockman, H. A.; Chiariello, Massimo. - In: BASIC RESEARCH IN CARDIOLOGY. - ISSN 0300-8428. - STAMPA. - 103:1(2008), pp. 22-30. [10.1007/s00395-007-0688-6]

Increased myocardial contractility and enhanced exercise function in transgenic mice overexpressing either adenylyl cyclase 5 or 8.

ESPOSITO, GIOVANNI;PERRINO, CINZIA;CHIARIELLO, MASSIMO
2008

Abstract

OBJECTIVE: ss-adrenergic receptors (ssARs) are powerful regulators 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. METHODS: 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. RESULTS: 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. CONCLUSIONS: 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.
2008
Increased myocardial contractility and enhanced exercise function in transgenic mice overexpressing either adenylyl cyclase 5 or 8 / Esposito, Giovanni; Perrino, Cinzia; Ozaki, T.; Takaoka, H.; Defer, N.; Petretta, M. P.; De Angelis, M. C.; Mao, L.; Hanoune, J.; Rockman, H. A.; Chiariello, Massimo. - In: BASIC RESEARCH IN CARDIOLOGY. - ISSN 0300-8428. - STAMPA. - 103:1(2008), pp. 22-30. [10.1007/s00395-007-0688-6]
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/11588/341356
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