he contribution of phosphodiesterases to cardiac dysfunction in rats with metabolic syndrome induced by a high-carbohydrate diet

Metabolic syndrome (MetS) is a cluster of risk factors such as insulin resistance among others, underlying the development of diabetes and/or cardiovascular diseases. Studies show a close relationship between cardiac dysfunction and abnormal cAMP catabolism, contributing to pathological-remodeling. Taken into consideration the importance of therapeutic enhancement of cAMP by stimulating its synthesis via suppression of PDEs, we examined their roles on cardiac dysfunction in high carbohydrate diet-induced MetS-rats. We first demonstrated significantly high expression levels of PDE3 and PDE4, the most highly expressed subtypes, together with the depressed cAMP-level in heart-tissue from MetS-rats. Second, we demonstrated these PDEs activities by using either their basal or PDE inhibitor-induced intracellular levels of cAMP and Ca2+, the transient intracellular Ca2+ changes under electrical-stimulation, isometric contractions in papillary muscle strips and some key signaling proteins (such as RyR2, PLN, PP1A and PKA) responsible for the Ca2+ homeostasis in isolated cardiomyocytes from MetS-rats. Overall, our present data demonstrated that the clear recovery in decreased basal cAMP level, increased protein expression levels of PDE3 and PDE4 as well as positive responses in the altered Ca2+ homeostasis to PDEs inhibitors can provide important insights on the roles of activated PDEs in depressed contractile activity of hearts from MetS-rats.The accepted manuscript in pdf format is listed with the files at the bottom of this page. The presentation of the authors' names and (or) special characters in the title of the manuscript may differ slightly between what is listed on this page and what is listed in the pdf file of the accepted manuscript; that in the pdf file of the accepted manuscript is what was submitted by the author