Departamento de Ciencias Biológicas, Cátedra de Biología Celular y Molecular, Facultad de Farmacia y Bioquímica, Universidad de Buenos Aires, Buenos Aires, Argentina.
Departamento de Ciencias Biológicas, Cátedra de Biología Celular y Molecular, Facultad de Farmacia y Bioquímica, Universidad de Buenos Aires, CONICET, Buenos Aires, Argentina.
Clin Sci (Lond). 2022 Sep 16;136(17):1303-1339. doi: 10.1042/CS20220293.
The developmental origin of hypertension and renal disease is a concept highly supported by strong evidence coming from both human and animal studies. During development there are periods in which the organs are more vulnerable to stressors. Such periods of susceptibility are also called 'sensitive windows of exposure'. It was shown that as earlier an adverse event occurs; the greater are the consequences for health impairment. However, evidence show that the postnatal period is also quite important for hypertension and renal disease programming, especially in rodents because they complete nephrogenesis postnatally, and it is also important during preterm human birth. Considering that the developing kidney is vulnerable to early-life stressors, renal programming is a key element in the developmental programming of hypertension and renal disease. The purpose of this review is to highlight the great number of studies, most of them performed in animal models, showing the broad range of stressors involved in hypertension and renal disease programming, with a particular focus on the stressors that occur during the early postnatal period. These stressors mainly include undernutrition or specific nutritional deficits, chronic behavioral stress, exposure to environmental chemicals, and pharmacological treatments that affect some important factors involved in renal physiology. We also discuss the common molecular mechanisms that are activated by the mentioned stressors and that promote the appearance of these adult diseases, with a brief description on some reprogramming strategies, which is a relatively new and promising field to treat or to prevent these diseases.
高血压和肾脏疾病的发育起源是一个概念,得到了来自人类和动物研究的强有力证据的高度支持。在发育过程中,器官有一些时期更容易受到压力源的影响。这些易感性时期也被称为“暴露敏感窗口”。研究表明,早期发生的不良事件对健康损害的后果越大。然而,有证据表明,出生后时期对于高血压和肾脏疾病的编程也非常重要,特别是在啮齿动物中,因为它们在出生后完成了肾发生,而且在人类早产期间也很重要。考虑到发育中的肾脏容易受到早期生活压力源的影响,肾脏编程是高血压和肾脏疾病发育编程的关键因素。本综述的目的是强调大量的研究,其中大多数是在动物模型中进行的,这些研究表明了广泛的压力源参与了高血压和肾脏疾病的编程,特别关注了出生后早期发生的压力源。这些压力源主要包括营养不良或特定的营养缺乏、慢性行为应激、暴露于环境化学物质以及影响肾脏生理学的某些重要因素的药物治疗。我们还讨论了被提及的压力源激活的常见分子机制,这些机制促进了这些成年疾病的出现,并简要描述了一些重新编程策略,这是一个相对较新且有前途的领域,可以治疗或预防这些疾病。