Departments of Obstetrics and Gynaecology and of Physiology, University of Alberta, Edmonton, Canada; Women and Children's Health Research Institute, Edmonton, Canada; and Cardiovascular Research Centre, Edmonton, Canada.
Physiol Rev. 2016 Apr;96(2):549-603. doi: 10.1152/physrev.00015.2015.
The developmental origins of health and disease theory is based on evidence that a suboptimal environment during fetal and neonatal development can significantly impact the evolution of adult-onset disease. Abundant evidence exists that a compromised prenatal (and early postnatal) environment leads to an increased risk of hypertension later in life. Hypertension is a silent, chronic, and progressive disease defined by elevated blood pressure (>140/90 mmHg) and is strongly correlated with cardiovascular morbidity/mortality. The pathophysiological mechanisms, however, are complex and poorly understood, and hypertension continues to be one of the most resilient health problems in modern society. Research into the programming of hypertension has proposed pharmacological treatment strategies to reverse and/or prevent disease. In addition, modifications to the lifestyle of pregnant women might impart far-reaching benefits to the health of their children. As more information is discovered, more successful management of hypertension can be expected to follow; however, while pregnancy complications such as fetal growth restriction, preeclampsia, preterm birth, etc., continue to occur, their offspring will be at increased risk for hypertension. This article reviews the current knowledge surrounding the developmental origins of hypertension, with a focus on mechanistic pathways and targets for therapeutic and pharmacologic interventions.
健康与疾病起源理论认为,胎儿和新生儿期发育过程中所处的不良环境会显著影响成年后疾病的发生。大量证据表明,产前(和产后早期)环境受损会增加日后发生高血压的风险。高血压是一种无声的、慢性的、进行性疾病,其特征为血压升高(>140/90mmHg),与心血管发病率/死亡率密切相关。然而,其病理生理机制复杂且尚未完全阐明,高血压仍是现代社会最顽固的健康问题之一。有关高血压形成机制的研究提出了药物治疗策略,以逆转和/或预防疾病。此外,改变孕妇的生活方式可能会给其子女的健康带来深远的益处。随着更多信息的发现,预计高血压的管理将更加成功;然而,只要胎儿生长受限、子痫前期、早产等妊娠并发症继续发生,其后代发生高血压的风险就会增加。本文综述了高血压起源的现有知识,重点介绍了治疗和药物干预的机制途径和靶点。