Adiponectin downregulation is associated with volume overload-induced myocyte dysfunction in rats

Aim： Adiponectin has been reported to exert protective effects during pathological ventricular remodeling, but the role of adiponectin in volume overload-induced heart failure remains unclear. In this study we investigated the effect of adiponectin on cardiac myocyte contractile dysfunction following volume overload in rats. Methods： Volume overload was surgically induced in rats by infrarenal aorta-vena cava fistula. The rats were intravenously adminis- tered adenoviral adiponectin at 2-, 6- and 9-weeks following fistula. The protein expression of adiponectin, adiponectin receptors （Adi- poR1/R2 and T-cadherin） and AMPK activity were measured using Western blot analyses. Isolated ventricular myocytes were prepared at 12 weeks post-fistula to examine the contractile performance of myocytes and intracellular Ca2＋ transient. Results： A-V fistula resulted in significant reductions in serum and myocardial adiponectin levels, myocardial adiponectin receptor （AdipoR1/R2 and T-cadherin） levels, as well as myocardial AMPK activity. Consistent with these changes, the isolated myocytes exhib- ited significant depression in cell shortening and intracellular Ca2＋ transient. Administration of adenoviral adiponectin significantly increased serum adiponectin levels and prevented myocyte contractile dysfunction in fistula rats. Furthermore, pretreatment of iso- lated myocytes with recombinant adiponectin （2.5 μg/mL） significantly improved their contractile performance in fistula rats, but had no effects in control or adenoviral adiponectin-administered rats. Conclusion： These results demonstrate a positive correlation between adiponectin downregulation and volume overload-induced yen- tricular remodeling. Adiponectin plays a protective role in volume overload-induced heart failure.