Key result
Isoproterenol-induced beta1-adrenoceptor signal transduction was unaltered by pressure overload at 4 weeks, augmented by volume overload at 4 weeks, and attenuated by both at 24 weeks.
In a rat model, alterations in beta1-adrenoceptor signal transduction are dependent on both the type (pressure vs. volume overload) and stage (4 vs. 24 weeks) of cardiac hypertrophy.
Overload type and stage shape beta1 signaling in rat hypertrophy; leaves open translation to human HF therapy.
To examine whether cardiac hypertrophy is associated with changes in beta-adrenoceptor signal transduction mechanisms, pressure overload (PO) was induced by occlusion of the abdominal aorta and volume overload (VO) by creation of an aortocaval shunt for 4 and 24 wk in rats. After hemodynamic assessment of the animals, the left ventricular (LV) particulate fraction was isolated for measurement of beta(1)-adrenoceptors and adenylyl cyclase activity, and cardiomyocytes were isolated for monitoring of the intracellular Ca(2+) concentration. Although PO and VO produced cardiac hypertrophy and increased LV end-diastolic pressure at 4 wk, cardiac function was increased in animals subjected to PO but remained unaltered in animals subjected to VO. Cardiac hypertrophy and increased LV end-diastolic pressure were associated with depressed cardiac function at 24 wk of PO or VO, but clinical signs of congestive heart failure were evident only in animals subjected to VO. Isoproterenol-induced increases in cardiac function, activation of adenylyl cyclase activity, and increase in intracellular Ca(2+) concentration, as well as beta(1)-adrenoceptor density, were unaltered by PO at 4 wk, augmented by VO at 4 wk, and attenuated by PO and VO at 24 wk. These results suggest that alterations in beta(1)-adrenoceptor signal transduction are dependent on the type and stage of cardiac hypertrophy.
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Sethi et al. (2006) studied Cardiac hypertrophy. Pressure overload and volume overload was evaluated on beta1-adrenoceptor signal transduction (isoproterenol-induced increases in cardiac function, adenylyl cyclase activity, intracellular Ca2+ concentration, beta1-adrenoceptor density). Isoproterenol-induced beta1-adrenoceptor signal transduction was unaltered by pressure overload at 4 weeks, augmented by volume overload at 4 weeks, and attenuated by both at 24 weeks.
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