Maternal diet during gestation and lactation modifies the severity of salt-induced hypertension and renal injury in Dahl salt-sensitive rats.
Maternal diet during gestation and lactation modifies the severity of salt-induced hypertension and renal injury in Dahl salt-sensitive rats.
复制标题
DOI：
10.1161/hypertensionaha.114.04179
复制
发表时间：
2015-02
期刊：
影响因子：
--
通讯作者：
Cowley AW Jr
中科院分区：
文献类型：
--
作者：
Geurts AM;Mattson DL;Liu P;Cabacungan E;Skelton MM;Kurth TM;Yang C;Endres BT;Klotz J;Liang M;Cowley AW Jr
父母或生命早期的环境暴露可能会影响成年人的疾病发展。我们发现，与以酪蛋白为基础的AIN-76A饲料饲养的SS/JrHsdMcwi大鼠(SS/MCW)相比，多代饲养的Dahl SS/JrHsdMcwiCrl(SS/CRL)大鼠的高血压和高盐饮食所致的肾脏损伤显著减轻(平均动脉压116±9比154±25毫米汞柱；尿白蛋白排泄量23±12比170±80 mg/天)。对肾脏外髓的RNA-SEQ分析发现，在SS/MCW和SS/CRL大鼠中，分别有129和82个基因对高盐饮食做出了独特的反应，以及SS亚系之间的微小遗传差异。在SS/MCW株中对盐作出反应的129个基因包括许多与人类高血压、心血管疾病或肾脏疾病相关的同源基因。为了缩小暴露的临界窗口，我们进行了胚胎移植实验，将一个群体(SS/MCW或SS/CRL)的单细胞胚胎移植给另一个群体的代孕母亲，父母和代孕母亲保持各自的原始饮食。仔猪断奶后均饲喂AIN-76A日粮。从SS/CRL胚胎移植到SS/MCW代孕母亲所发育的大鼠，盐诱导的高血压和肾脏损伤显著加剧。相反，从SS/MCW胚胎移植到SS/CRL代孕母亲所发育的大鼠的盐源性高血压和肾脏损伤显著减轻。总之，这些数据表明，孕期-哺乳期的母体饮食对成年SS大鼠盐源性高血压和肾脏损伤的发生有实质性的影响。
Environmental exposure of parents or early in life may affect disease development in adults. We found that hypertension and renal injury induced by a high-salt diet were substantially attenuated in Dahl SS/JrHsdMcwiCrl (SS/Crl) rats that had been maintained for many generations on the grain-based 5L2F diet compared to SS/JrHsdMcwi rats (SS/Mcw) maintained on the casein-based AIN-76A diet (mean arterial pressure 116±9 vs. 154±25 mmHg; urinary albumin excretion 23±12 vs. 170±80 mg/day). RNA-seq analysis of the renal outer medulla identified 129 and 82 genes responding to a high-salt diet uniquely in SS/Mcw and SS/Crl rats, respectively, along with minor genetic differences between the SS substrains. The 129 genes responding to salt in the SS/Mcw strain included numerous genes with homologs associated with hypertension, cardiovascular disease, or renal disease in human. To narrow the critical window of exposure, we performed embryo transfer experiments in which single-cell embryos from one colony (SS/Mcw or SS/Crl) were transferred to surrogate mothers from the other colony, with parents and surrogate mothers maintained on their respective original diet. All offspring were fed the AIN-76A diet after weaning. Salt-induced hypertension and renal injury were substantially exacerbated in rats developed from SS/Crl embryos transferred to SS/Mcw surrogate mothers. Conversely, salt-induced hypertension and renal injury were significantly attenuated in rats developed from SS/Mcw embryos transferred to SS/Crl surrogate mothers. Together, the data suggests that maternal diet during the gestational-lactational period has substantial effects on the development of salt-induced hypertension and renal injury in adult SS rats.