The contribution of phosphodiesterases to cardiac dysfunction in rats with metabolic syndrome induced by a high-carbohydrate diet.
Can J Physiol Pharmacol
; 97(11): 1064-1072, 2019 Nov.
Article
em En
| MEDLINE
| ID: mdl-31299169
ABSTRACT
Metabolic syndrome (MetS) is a cluster of risk factors, including 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, which contributes to pathological remodelling. Stimulating the synthesis of cAMP via suppression of phosphodiesterases (PDEs) has positive therapeutic effects. Therefore, we examined the role of PDEs 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 depressed cAMP levels in heart tissue from MetS rats. Second, we demonstrated the activity of these PDEs 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 signalling proteins (such as RyR2, PLN, PP1A, and PKA) are responsible for the Ca2+ homeostasis in isolated cardiomyocytes from MetS rats. The clear recovery in decreased basal cAMP levels, increased protein expression levels of PDE3 and PDE4, and positive responses in the altered Ca2+ homeostasis to PDE inhibitors as seen in our study can provide important insights about the roles of activated PDEs in depressed contractile activity in hearts from MetS rats.
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Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Carboidratos da Dieta
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Síndrome Metabólica
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Nucleotídeo Cíclico Fosfodiesterase do Tipo 3
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Nucleotídeo Cíclico Fosfodiesterase do Tipo 4
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Coração
Tipo de estudo:
Risk_factors_studies
Limite:
Animals
Idioma:
En
Ano de publicação:
2019
Tipo de documento:
Article