Salt accelerates aldosterone-induced cardiac remodeling in the absence of guanylyl cyclase-A signaling.
Salt accelerates aldosterone-induced cardiac remodeling in the absence of guanylyl cyclase-A signaling.
复制标题
在鸟苷酸环化酶-A 信号传导缺失的情况下，盐会加速醛固酮诱导的心脏重塑。
DOI：
10.1016/j.lfs.2016.09.011
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发表时间：
2016
期刊：
影响因子：
6.1
通讯作者：
Saito Y.
中科院分区：
文献类型：
--
作者：
Nakagawa H;Somekawa S;Onoue K;Kumazawa T;Ueda T;Seno A;Nakada Y;Nakano T;Matsui M;Soeda T;Okayama S;Kawakami R;Kawata H;Okura H;Saito Y.
目的过量的钠可导致心血管疾病的发生，并与增强肾素-血管紧张素-醛固酮系统（RAAS）有关。利钠肽是钠调节剂，通过抵消RAAS来防止病理性心脏改变。然而，利钠肽是否抑制心脏不良改变中的钠效应尚不清楚。在这里，我们研究了过量的盐摄入是否会加剧心脏重塑与受损的利钠肽signaling.Materials和methodsMice缺乏基因编码的利钠肽受体，鸟苷酸环化酶-A（GC-A），和野生型小鼠给予无论是车辆物质或降压剂量的醛固酮（100 ng/kg/min），同时给予低盐（0.001%NaCl）、正常盐（0.6%NaCl）或高盐饮食（6.0%NaCl）4周。然后将小鼠处死，通过组织学和RT-PCR.Key findingsSalt负荷评估心脏，在野生型小鼠的载体和醛固酮组中，盐负荷没有诱导心脏变化。另一方面，在给予醛固酮的GC-A敲除（KO）小鼠中，心脏肥大和间质纤维化以盐依赖性方式显著加重，并且与肥大、纤维化和氧化应激条件相关的基因表达增强相关。值得注意的是，过量的盐摄入增加了醛固酮给药的GC-A KO小鼠中Sgk 1、血清和糖皮质激素反应性激酶-1的表达。这些分子的变化在野生型mice中没有观察到。SignificanceThe本研究的结果表明，过量的盐摄入诱导心脏重塑与醛固酮给药在GC-A KO小鼠，表明GC-A信号减弱了有害的盐的影响，醛固酮诱导的心脏重塑。
AimsExcess sodium causes the development of cardiovascular diseases in conjunction with enhancing renin-angiotensin-aldosterone system (RAAS). Natriuretic peptides are sodium regulators and prevent pathological cardiac alterations by counteracting RAAS. However, it is unknown whether natriuretic peptides inhibit the sodium effect in adverse cardiac alterations. Here, we investigated whether excess salt intake could exacerbate cardiac remodeling in mice with impaired natriuretic peptide signaling.Materials and methodsMice lacking the gene encoding the natriuretic peptide receptor, guanylyl cyclase-A (GC-A), and wild-type mice were administered with either a vehicle substance or a subpressor dose of aldosterone (100 ng/kg/min), alongside low salt (0.001% NaCl), normal salt (0.6% NaCl), or high salt diets (6.0% NaCl) for four weeks. Mice were then sacrificed and the hearts were evaluated by histology and RT-PCR.Key findingsSalt load did not induce cardiac changes in vehicle and aldosterone groups in wild-type mice. On the other hand, cardiac hypertrophy and interstitial fibrosis were significantly exacerbated in a salt dependent manner in GC-A knockout (KO) mice administered aldosterone, and were associated with enhanced gene expression relevant to hypertrophy, fibrosis, and oxidative stress conditions. Of note, excess salt intake increased the expression of Sgk1, serum and glucocorticoid responsive kinase-1, in aldosterone-administered GC-A KO mice. These molecular changes were not observed in wild-type mice.SignificanceThe results of the present study demonstrate that excess salt intake induced cardiac remodeling in conjunction with aldosterone administration in GC-A KO mice, indicating that GC-A signaling attenuated the deleterious salt effect in aldosterone-induced cardiac remodeling.