Project Summary The GENERAL AIM of this proposal is to qualitatively advance knowledge on urinary metabolic phenotypes and biochemical pathways associated with the direct effect on blood pressure (BP) of high sodium (Na) intake and the inverse BP effect (BP reduction) of the DASH/OmniHeart- like eating pattern. To achieve this aim, we will identify and quantify key metabolites related to these contrasting BP influences, and use state-of-the-art chemometrics, statistical spectroscopy, computational network and pathway modeling tools to identify and map de novo pathways associated with Na-BP and DASH/OmniHeart-BP. We will then test and validate the INTERMAP derived metabolites and pathways using available data and samples from the INTERMAP China Prospective (ICP) Study, the Urinary Sodium Study (USS), and the OmniHeart Trial. The goal is to develop more focused and effective strategies for population- wide BP lowering through improved non-pharmacologic approaches, primarily nutritional, as well as to identify new targets for drug intervention. To our knowledge, this is the first investigation to identify urinary metabolites and associated pathways related to Na-BP and DASH/OmniHeart-BP, link these to dietary and other data, and with extensive validation in other cohorts, prospective and trial data.