In vivo and in vitro endothelial effects of taurine in protein restriction

Abstract

Nutritional deficiency is a public health problem that affects mainly children of the de-veloping countries. Intrauterine and early life malnutrition favor metabolic and cardio-vascular disorders associated with endothelial dysfunction such as hypertension and Type 2 Diabetes. In this context, the insulinotropic, vasodilator and antioxidant amino acid taurine may act as a complementary therapy. However, the mechanisms by which taurine can be protective against endothelial dysfunction and hypertension still need to be elucidated. Therefore, this proposal aims to investigate the intracellular mechanisms associated with the endothelial effects of taurine following protein restriction. For this, we will use two methodological approaches: 1) aminoacid restriction in vitro through the exposure of endothelial cells to low amino acid content; 2) protein restriction in vivo by feeding post-weaned mice with an isocaloric low-protein diet (6% protein) for 90 days. In endothelial cells exposed to amino acid restriction and/or taurine, Nitric Oxide (NO) production and insulin signaling pathway will be evaluated. Mice fed low-protein diet will be concomitantly treated with taurine (2.5%). At the end of treatment, the systolic blood pressure will be evaluated by tail-cuff plethysmography and small mesenteric arteries and interlobular pancreatic arteries will be isolated for vascular function, protein expression and NO production. This study should contribute to elucidate potential therapeutic mechanisms of taurine in cardiovascular diseases associated with metabolic disorders. (AU)