Authors: Ayse L Mindikoglu Thomas C Dowling David J Schaub William R Hutson Darryn R Potosky Robert H Christenson Rolf N Barth John C LaMattina Steven I Hanish Matthew R Weir JeanPierre Raufman
Publish Date: 2015/07/05
Volume: 60, Issue: 11, Pages: 3491-3494
Abstract
Phosphodiesterase5 PDE5 inhibitors play an important role in the treatment of complications of cirrhosis They have been used successfully to treat portopulmonary hypertension PPHTN 1 2 3 4 a complication in 5 of subjects with cirrhosis 5 Additionally previous studies showed that PDE5 inhibitors reduced portal pressures and hepatic venous pressure gradients thereby improving hemodynamics in cirrhosis 6 7 8 Moreover in cirrhotic rats PDE5 inhibitors increased fractional excretion of Na reduced plasma renin levels and improved renal blood flow and glomerular filtration rate 9In cirrhosis diminished intrahepatic nitric oxide NO levels 6 are associated with elevated asymmetric dimethylarginine levels that inhibit NO synthesis by competing with larginine for NO synthase 10 11 In turn reduced intrahepatic NO levels result in dysfunction of NOactivated guanylate cyclase and consequently reduced sinusoidal cyclic guanosine 3′ 5′The authors thank Heather L Rebuck MT ASCP CLS NCA and Sharon Y Huang MT Clinical Chemistry Research Lab University of Maryland Baltimore University of Maryland General Clinical Research Center Staff and Galina Bikzhanova PhD Discovery Bioanalytical Chemistry Covance Laboratories Inc for their supportThe project described was supported in part by Grant Number 5 K23 DK08900805 from the National Institutes of Health NIH National Institute of Diabetes and Digestive and Kidney Diseases to Ayse L Mindikoglu MD MPH and its contents are solely the responsibility of the authors and do not necessarily represent the official views of the National Institute of Diabetes and Digestive and Kidney Diseases or the NIH This work was also supported by the University of Maryland School of Medicine Department of Medicine funds to Ayse L Mindikoglu MD MPH University of Maryland Clinical Translational Science Institute and the University of Maryland General Clinical Research Center
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