title: Reprogramming: A Preventive Strategy in Hypertension Focusing on the Kidney.
abstract: Adulthood hypertension can be programmed in response to a suboptimal environment in early life. However, developmental plasticity also implies that one can prevent hypertension in adult life by administrating appropriate compounds during early development. We have termed this reprogramming. While the risk of hypertension has been assessed in many mother-child cohorts of human developmental programming, interventions necessary to prove causation and provide a reprogramming strategy are lacking. Since the developing kidney is particularly vulnerable to environmental insults and blood pressure is determined by kidney function, renal programming is considered key in developmental programming of hypertension. Common pathways, whereby both genetic and acquired developmental programming converge into the same phenotype, have been recognized. For instance, the same reprogramming interventions aimed at shifting nitric oxide (NO)-reactive oxygen species (ROS) balance, such as perinatal citrulline or melatonin supplements, can be protective in both genetic and developmentally programmed hypertension. Furthermore, a significantly increased expression of gene Ephx2 (soluble epoxide hydrolase) was noted in both genetic and acquired animal models of hypertension. Since a suboptimal environment is often multifactorial, such common reprogramming pathways are a practical finding for translation to the clinic. This review provides an overview of potential clinical applications of reprogramming strategies to prevent programmed hypertension. We emphasize the kidney in the following areas: mechanistic insights from human studies and animal models to interpret programmed hypertension; identified risk factors of human programmed hypertension from mother-child cohorts; and the impact of reprogramming strategies on programmed hypertension from animal models. It is critical that the observed effects on developmental reprogramming in animal models are replicated in human studies.
authors.affiliation: Departments of Pediatrics, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Kaohsiung 833, Taiwan. tainyl@hotmail.com.|Institute for Translational Research in Biomedicine, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Kaohsiung 833, Taiwan. tainyl@hotmail.com.
authors.forename: You-Lin
authors.initials: YL
authors.lastname: Tain
authors.affiliation: Department of Nephrology and Hypertension, Laboratory of Renal and Vascular Biology, University Medical Center Utrecht, POB 85500, 3508 GA Utrecht, The Netherlands. J.A.Joles@umcutrecht.nl.
authors.forename: Jaap A
authors.initials: JA
authors.lastname: Joles
mesh_terms: D000818:Animals; D000959:Antihypertensive Agents / Q000627:therapeutic use; D004851:Epoxide Hydrolases / Q000378:metabolism; D006801:Humans; D006973:Hypertension / Q000188:drug therapy / Q000378:metabolism / Q000517:prevention & control*; D007668:Kidney / Q000378:metabolism*; D058246:Prehypertension / Q000188:drug therapy / Q000378:metabolism; D017382:Reactive Oxygen Species / Q000378:metabolism
chemical_list: D000959:Antihypertensive Agents; D017382:Reactive Oxygen Species; D004851:Epoxide Hydrolases; C506428:EPHX2 protein, human
keywords: developmental programming; nitric oxide; perinatal supplements; reactive oxygen species; soluble epoxide hydrolase