Translational research and clinical application of the natriuretic peptide system in the kidney.

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Natriuretic peptide family (ANP, BNP, and CNP) exert potent diuretic, natriuretic and vasorelaxing properties, as well as the inhibition of the renin-angiotensin-aldosterone system. We investigated the role of natriuretic peptides in renal disease and its complications.1. Preparation of CNP-transgenic mice (CNP-Tg) and effects of CNP on renal injury :CNP acts as a local hormone in the vessel, bone and kidney. Human SAP promoter-driven CNP-Tg exhibited enhanced bone growth as a result of excess circulating CNP. CNP-Tg showed ameliorated renal fibrosis and macrophage infiltration upon obstructive nephropathy model.2. Role of GC-A (a receptor for ANP and BNP) and aldosterone in glomerular injury :GC-A is expressed abundantly in renal tubules, but its role in glomerular injury is unknown. When GC-A knockout mice were subjected to aldosterone and high salt, massive proteinuria with marked podocyte injury was observed, which was alleviated with the MR antagonist, ARB or antioxidant.3. Role of ANP and BNP in peritoneal sclerosis :Peritoneal sclerosis is a serious complication in chronic peritoneal dialysis, but the effective treatment is not established yet. Subcutaneous ANP administration as well as chronic BNP excess in transgenic mice effectively ameliorated peritoneal adhesion in a mouse model of peritoneal sclerosis.These results indicate that natriuretic peptides will have a various therapeutic potential in renal disease and related pathophysiological conditions.