PDF(Pubmed)
Abstract：
BACKGROUND: Spironolactone (SPI) is a diuretic widely used to treat cardiovascular diseases (CVD) and is non-specific for mineralocorticoid receptors (MR) and with an affinity for progesterone (PR) and androgen (AR) receptors. Since 2009, it has been suggested that pharmaceuticals are emerging contaminants (called EDC), and recently, it was reported that most EDC are AR and MR antagonists and estrogen receptors (ER) agonists. Concerning SPI, endocrine-disrupting effects were observed in female western mosquitofish, but there are still no data regarding the SPI effects as a possible human EDC.
METHODS: In this work, aortic rings were used to analyze the contractility effects of SPI and the mode of action concerning the involvement of Ca2+ channels and endothelial pathways. Moreover, cytotoxic effects were analyzed by MTT assays.
RESULTS: SPI induces vasodilation in the rat aorta by endothelium-dependent mechanisms involving NO and by endothelium-independent mechanisms blocking Ca2+ channels. Moreover, a non-monotonic effect characteristic of EDC was observed for SPI-induced decrease in cell viability.
CONCLUSIONS: Our findings suggest that SPI may act as an EDC at a human level. However, ex vivo studies with human arteries should be carried out to better understand this drug\'s implications for human health and future generations.
METHODS: In this work, aortic rings were used to analyze the contractility effects of SPI and the mode of action concerning the involvement of Ca2+ channels and endothelial pathways. Moreover, cytotoxic effects were analyzed by MTT assays.
RESULTS: SPI induces vasodilation in the rat aorta by endothelium-dependent mechanisms involving NO and by endothelium-independent mechanisms blocking Ca2+ channels. Moreover, a non-monotonic effect characteristic of EDC was observed for SPI-induced decrease in cell viability.
CONCLUSIONS: Our findings suggest that SPI may act as an EDC at a human level. However, ex vivo studies with human arteries should be carried out to better understand this drug\'s implications for human health and future generations.
摘要：
背景：螺内酯（SPI）是一种广泛用于治疗心血管疾病（CVD）的利尿剂，对盐皮质激素受体（MR）无特异性，对孕酮（PR）和雄激素（AR）受体具有亲和力。自2009年以来，有人认为药物是新兴的污染物(称为EDC)，最近,据报道，大多数EDC是AR和MR拮抗剂和雌激素受体（ER）激动剂。关于SPI，在雌性西方蚊子中观察到内分泌干扰作用，但是仍然没有关于SPI效应作为可能的人类EDC的数据。
方法：在这项工作中，使用主动脉环来分析SPI的收缩作用以及与Ca2通道和内皮途径有关的作用方式。此外，通过MTT试验分析细胞毒性作用。
结果：SPI通过涉及NO的内皮依赖性机制和阻断Ca2+通道的非内皮依赖性机制诱导大鼠主动脉血管舒张。此外，对于SPI诱导的细胞活力降低,观察到EDC的非单调效应特征。
结论：我们的研究结果表明，SPI可能在人类水平上充当EDC。然而,为了更好地了解这种药物对人类健康和后代的影响，应进行人体动脉的离体研究。
方法：在这项工作中，使用主动脉环来分析SPI的收缩作用以及与Ca2通道和内皮途径有关的作用方式。此外，通过MTT试验分析细胞毒性作用。
结果：SPI通过涉及NO的内皮依赖性机制和阻断Ca2+通道的非内皮依赖性机制诱导大鼠主动脉血管舒张。此外，对于SPI诱导的细胞活力降低,观察到EDC的非单调效应特征。
结论：我们的研究结果表明，SPI可能在人类水平上充当EDC。然而,为了更好地了解这种药物对人类健康和后代的影响，应进行人体动脉的离体研究。
