Targeting on Asymmetric Dimethylarginine-Related Nitric Oxide-Reactive Oxygen Species Imbalance to Reprogram the Development of Hypertension

Adult-onset diseases, including hypertension, can originate from early life, known as the developmental origins of health and disease (DOHaD). Because the developing kidney is vulnerable to early-life insults, renal programming is considered key in the developmental programming of hypertension. Asymmetric dimethylarginine (ADMA), an endogenous nitric oxide (NO) synthase inhibitor, can regulate the NO–reactive oxygen species (ROS) balance, and is involved in the development of hypertension. Reprogramming interventions aimed at NO-ROS balance can be protective in both genetic and developmentally programmed hypertension. Here we review several emergent themes of the DOHaD approach regarding the impact of ADMA-related NO-ROS imbalance on programmed hypertension. We focus on the kidney in the following areas: mechanistic insights to interpret programmed hypertension; the impact of ADMA-related NO-ROS imbalance in both genetic and acquired animal models of hypertension; alterations of the renal transcriptome in response to ADMA in the developing kidney; and reprogramming strategies targeting ADMA-related NO-ROS balance to prevent programmed hypertension