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.