PROJECT SUMMARY Non-dipping type of nocturnal blood pressure (BP) is common even among treated hypertensives and is associated with a nearly two-fold higher risk of adverse cardiovascular events. Obesity impacts nearly 40% of American adults, and obese individuals have a high prevalence of hypertension and non-dipping type of nocturnal BP. The natriuretic peptides (NPs) are hormones produced by the heart that regulate BP rhythm by causing dilatation of vessels, sodium excretion, and inhibition of the renin-angiotensin-aldosterone system (RAAS). We have demonstrated that there exists a diurnal rhythm (24-hour rhythm) of NPs, which tracks closely with the BP rhythm and is in an antiphase relationship with the rhythm of the RAAS hormones. Obese individuals have lower NP levels throughout the day and a misaligned NP-RAAS-BP rhythm. LCZ696 is an FDA approved inhibitor of neprilysin (an NP degrading enzyme) that augments the NP levels and also suppresses the RAAS. Hence, the confluence of putative NP deficiency and the NP- RAAS-BP rhythm misalignment in obese may contribute to the high-risk nocturnal non-dipping BP profile seen commonly among obese individuals. Chronophamacology (controlling the time of medication administration) to synchronize the NP-RAAS-BP axis inherent biological rhythms may help control the nocturnal BP dipping pattern in obese individuals. We hypothesize that nighttime administration of NP- RAAS-BP axis therapy in obese hypertensive individuals will resynchronize their physiological rhythm patterns and help to improve their nocturnal BP profile. We plan to conduct a patient-oriented physiological, clinical trial to assess the effect of timing of administration of NP-RAAS-BP axis therapy (to target the rhythm misalignment) and the type of NP-RAAS-BP axis therapy (to target NP deficiency) on restoring the nocturnal BP dipping in obese hypertensives with non-dipping. We will conduct a 2x2 factorial design trial, wherein individuals will be randomized t