Xanthine Oxidoreductase Inhibition Causes Reverse Remodeling in Rats With Dilated Cardiomyopathy
- 3 February 2006
- journal article
- Published by Ovid Technologies (Wolters Kluwer Health) in Circulation Research
- Vol. 98 (2), 271-279
- https://doi.org/10.1161/01.res.0000200181.59551.71
Abstract
Increased reactive oxygen species (ROS) generation is implicated in cardiac remodeling in heart failure (HF). As xanthine oxidoreductase (XOR) is 1 of the major sources of ROS, we tested whether XOR inhibition could improve cardiac performance and induce reverse remodeling in a model of established HF, the spontaneously hypertensive/HF (SHHF) rat. We randomized Wistar Kyoto (WKY, controls, 18 to 21 months) and SHHF (19 to 21 months) rats to oxypurinol (1 mmol/L; n=4 and n=15, respectively) or placebo (n=3 and n=10, respectively) orally for 4 weeks. At baseline, SHHF rats had decreased fractional shortening (FS) (31±3% versus 67±3% in WKY, PPP2+ handling pathways, supporting the idea that inhibiting XOR-derived oxidative stress substantially improves the HF phenotype.Keywords
This publication has 36 references indexed in Scilit:
- Chronic xanthine oxidase inhibition prevents myofibrillar protein oxidation and preserves cardiac function in a transgenic mouse model of cardiomyopathyAmerican Journal of Physiology-Heart and Circulatory Physiology, 2005
- The fall in creatine levels and creatine kinase isozyme changes in the failing heart are reversible: Complex post-transcriptional regulation of the components of the CK systemJournal of Molecular and Cellular Cardiology, 2005
- Xanthine oxidase inhibition ameliorates cardiovascular dysfunction in dogs with pacing-induced heart failureJournal of Molecular and Cellular Cardiology, 2005
- Pressure Overload–Induced Myocardial Hypertrophy in Mice Does Not Require gp91 phoxCirculation, 2004
- Vascular Oxidative Stress and Endothelial Dysfunction in Patients With Chronic Heart FailureCirculation, 2002
- Abnormal Ca 2+ Release, but Normal Ryanodine Receptors, in Canine and Human Heart FailureCirculation Research, 2002
- Enhanced Expression and Activity of Xanthine Oxidoreductase in the Failing HeartJournal of Molecular and Cellular Cardiology, 2000
- Post-infarction Heart Failure in the Rat is Associated with Distinct Alterations in Cardiac Myocyte Molecular PhenotypeJournal of Molecular and Cellular Cardiology, 1998
- Calcium handling proteins in the failing human heartBasic Research in Cardiology, 1997
- Control of Cardiac Gene Expression by Mechanical StressAnnual Review of Physiology, 1993