PR000457 (Project)

Description:Enhanced sensitivity of blood pressure to salt intake is observed in approximately 50% of hypertensive patients, reaching 75% in African American hypertensive patients. We recently discovered a novel role of abnormal cellular intermediary metabolism in hypertension in the Dahl salt-sensitive (SS) rat, the most commonly used polygenic, hereditary model of human salt-sensitive hypertension. We propose to test the hypothesis that blood pressure sensitivity to dietary salt intake in human is associated with metabolite changes in the urine. Leveraging the expertise and resources at the Mayo Clinic Metabolomics Resources Core, we propose to perform targeted LC/MS analysis and NMR spectra generation in urine samples obtained from a subset of subjects from the Dietary Approaches to Stop Hypertension – Sodium (DASH2) clinical trial and kidney tissue extract and urine samples from SS rats and a newly generated transgenic rat that overexpresses fumarase (SS.Fh1+). The study will be the first to systematically characterize urinary metabolite profiles associated with blood pressure response to salt in humans. The study is anticipated to generate new insight into the mechanisms (particularly renal mechanisms) underlying salt-sensitive hypertension. Findings of the proposed study could lead to an expanded clinical study as well as mechanistic studies in animal models.