de Almeida Lucas Ferreira, Coimbra Terezila Machado
Department of Physiology, Ribeirão Preto Medical School, University of São Paulo, Ribeirão Preto, Brazil.
Front Pediatr. 2019 Jul 17;7:296. doi: 10.3389/fped.2019.00296. eCollection 2019.
Environmental and nutritional factors during fetal and neonatal life can have long-lasting effects on renal functions and physiology and susceptibility to kidney disease in adulthood. All components of the renin-angiotensin system (RAS) are highly expressed in the kidneys during the period of renal development. The RAS plays a central role in the regulation of various cellular growth factors and stimulates adhesion molecules and cellular migration. The use of antagonists of this system during fetal development represents a major risk factor for hypertension, renal vascular dysfunction, and kidney medulla atrophy in adulthood. The inappropriate activation of the RAS by vitamin D (VitD) deficiency has been studied in recent years. Clinical and experimental studies have demonstrated an inverse relationship between circulating VitD levels and blood pressure, plasma and renin activity, and an increase in angiotensin II and the receptor AT. These data raise new questions about the importance of the integrity of the RAS during development since RAS pathway inhibitors and VitD deficiency have opposing functions. This is a literature review on the possible mechanisms by which antagonists of the RAS and VitD deficiency during fetal development provoke disturbances in kidney structure and function. Potential mechanisms are presented and discussed, and the possible pathways by which an imbalanced maternal RAS may negatively impact fetal development and have consequences in adulthood are also explored.
胎儿期和新生儿期的环境与营养因素可对成年后的肾功能、生理机能以及患肾病的易感性产生长期影响。在肾脏发育期间，肾素-血管紧张素系统（RAS）的所有组分在肾脏中均高表达。RAS在各种细胞生长因子的调节中起核心作用，并刺激黏附分子和细胞迁移。在胎儿发育期间使用该系统的拮抗剂是成年后发生高血压、肾血管功能障碍和肾髓质萎缩的主要危险因素。近年来，人们对维生素D（VitD）缺乏导致RAS不适当激活进行了研究。临床和实验研究表明，循环中VitD水平与血压、血浆和肾素活性呈负相关，且血管紧张素II和受体AT增加。由于RAS途径抑制剂和VitD缺乏具有相反的作用，这些数据引发了关于发育过程中RAS完整性重要性的新问题。这是一篇关于胎儿发育期间RAS拮抗剂和VitD缺乏引发肾脏结构和功能紊乱的可能机制的文献综述。文中介绍并讨论了潜在机制，还探讨了母体RAS失衡可能对胎儿发育产生负面影响并在成年期产生后果的可能途径。
