Área de Farmacología, Departamento de Medicina, Universidad de Oviedo, Oviedo, España.
Pharmacology. 2011;87(3-4):155-60. doi: 10.1159/000324172. Epub 2011 Mar 4.
Several mechanisms have been proposed to explain the acute cardiovascular effects elicited by androgens, such as vasodilation and positive inotropism. Phosphodiesterases (PDEs) are important modulators of cardiac contractility. However, an effect on PDEs by androgens in cardiac tissues has not previously been reported. In this study, extracts from rat ventricles and isolated left atria were assayed for cAMP-dependent PDE activity. To study the tissue selectivity, the enzymatic activity was also assayed in extracts from bovine tracheal smooth muscle and Chinese hamster ovary (CHO) cells. Functional assays were also performed with isolated atria. Testosterone, but not 5α- and 5β-dihydrotestosterone, inhibited cAMP-PDE activity in extracts from left ventricles and atria. In atria, the inhibition of cAMP-PDE activity was associated with an increase in intracellular levels of cAMP and a cardiotonic response. This effect was not elicited in tracheal muscle strips or CHO cell extracts, suggesting the possibility of tissue and cAMP-PDE selectivity. The results of these studies suggest a new mechanism of action of testosterone in the rat heart, which might contribute to the reported cardiotonic effect.
已经提出了几种机制来解释雄激素引起的急性心血管效应，如血管舒张和正性肌力作用。磷酸二酯酶（PDEs）是心肌收缩力的重要调节剂。然而，雄激素对心脏组织中 PDE 的作用以前尚未报道过。在这项研究中，从大鼠心室和分离的左心房中提取物测定 cAMP 依赖性 PDE 活性。为了研究组织选择性，还在牛气管平滑肌和中国仓鼠卵巢（CHO）细胞的提取物中测定了酶活性。还进行了功能测定与分离的心房。睾丸酮，但不是 5α-和 5β-二氢睾丸酮，抑制了左心室和心房提取物中的 cAMP-PDE 活性。在心房中，cAMP-PDE 活性的抑制与细胞内 cAMP 水平的增加和正性肌力反应有关。这种作用在气管肌条或 CHO 细胞提取物中未被引发，这表明存在组织和 cAMP-PDE 选择性的可能性。这些研究的结果表明了睾丸酮在大鼠心脏中的一种新的作用机制，这可能有助于解释报道的正性肌力作用。
