NOS3 and hypertensive disorder: The importance of enhanced methylation of the eNOS promoter in programming hypertension was also supported by the observation that treating pregnant and lactating SHR with pentaerythritoltetranitrate (PETN) a tolerance-free NO donor, decreased blood pressure of the female offspring and enhanced aortic eNOS expression, likely via distinct epigenetic changes of the promoter and transcriptional activation [43].