Abstract
Background Interstitial fibrosis is the common pathophysiological mechanism that leads to end organ failure of the both the heart and the kidney. Fibrosis is characterized by an excessive accumulation of myofibroblast-derived extracellular matrix. Peritubular capillary rarefaction precedes renal fibrosis and is secondary to the loss of capillary pericytes to the interstitium. Endothelial-derived C-type natriuretic peptide (CNP) has been demonstrated to have cGMP dependent anti-fibrotic properties most likely due to the interference with pro-fibrotic TGF-b signaling and may counteract the loss of the capillary pericytes. However, natriuretic peptides like CNP are rapidly degraded by neutral endopeptidase (NEP). In a unilateral urether obstruction (UUO) mouse model for kidney fibrosis we assessed the anti-fibrotic effects of Sol-1, a new orally-active compound (Solvay) that inhibits both neutral endopeptidase and endothelin.
Highlights
Interstitial fibrosis is the common pathophysiological mechanism that leads to end organ failure of the both the heart and the kidney
Mice (n=10 per group) subjected to urether obstruction (UUO) were treated for 1 week with either Solvent, SOL-1 (NEP-/ECE-inhibitor two doses), candoxatril or losartan and compared to sham operated animals
While the neutral endopeptidase (NEP) inhibitors had no significant effect on body weight, food and water intake, mean blood pressure or creatinine levels, they did increase cGMP levels in the urine and affected hematopoiesis in an anti-inflammatory way
Summary
Marina Aleksinskaya1*, Jacques Duijs, Jennifer Veth, Bettina Husen, Dania Reiche, Daniel Jasserand, Jo De Mey, Ton Rabelink, Anton Jan van Zonneveld. From 6th International Conference on cGMP: Generators, Effectors and Therapeutic Implications Erfurt, Germany. From 6th International Conference on cGMP: Generators, Effectors and Therapeutic Implications Erfurt, Germany. 28-30 June 2013
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