ATRIAL NATRIURETIC PEPTIDE: A FOCUS ON TISSUE HETEROGENEITY AND TISSUE SPECIFIC FUNCTION

Abstract

Human atrial natriuretic peptide (ANP) is a main regulator of our blood pressure/ volume homeostasis. It interacts with its receptor NPR-A and induces vasodilation, diuresis and natriuresis. Previously, our lab designed ANP analogues with exclusive diuretic (DGD-ANP) or vasodilatory (DRD-ANP) functions. To understand their tissue specific function, I evaluated the role of three natural NPR-A isoforms generated by alternative splicing. All three NPR-A isoforms failed to produce cGMP in mammalian cells but significantly reduced cGMP production of WT NPR-A. Thus, the differential expression of isoforms could play a role in tissue specific activity of ANP. In the kidney, ANP vasodilates afferent arterioles and vasoconstricts efferent arterioles to enhance diuresis. Although diuretic DGD-ANP shows similar effects as ANP, non-diuretic DRD-ANP has no such differential effects on renal arterioles. Thus, for the first time, I demonstrated the importance of signal transduction changes in renal arterioles for the distinct pharmacology of ANP analogues.