Pathophysiology of Renal DiseaseEffect of Chronic Renal Failure on Cardiac Contractile Function, Calcium Cycling, and Gene Expression of Proteins Important for Calcium Homeostasis in the RatKennedy, David; Omran, Eiad; Periyasamy, Sankaridrug M.; Nadoor, Jalaa; Priyadarshi, Anumeet; Willey, James C.; Malhotra, Deepak; Xie, Zijian; Shapiro, Joseph I. Author Information Departments of Medicine and Pharmacology, Medical College of Ohio, Toledo, Ohio. Correspondence to Dr. Joseph I. Shapiro, Chairman, Department of Medicine, Medical College of Ohio, 3120 Glendale Avenue, Toledo, Ohio 43614-5089. Phone: 419-383-6030; Fax: 419-383-6244; Accepted August 20, 2002 Received July 10, 2002 Journal of the American Society of Nephrology 14(1):p 90-97, January 2003. | DOI: 10.1097/01.ASN.0000037403.95126.03 Buy Metrics Abstract ABSTRACT. Patients with chronic renal failure frequently develop cardiac hypertrophy and diastolic dysfunction; however, the mechanisms by which this occurs are still unclear. Male Sprague-Dawley rats were subjected to 5/6 nephrectomy and studied for their isolated myocyte function, calcium cycling, and gene expression of proteins important in calcium homeostasis after 4 wk. Comparable rats subjected to suprarenal aortic banding for the same duration were used for comparison. Rats subjected to 5/6 nephrectomy and aortic banding developed comparable hypertension; however, rats subjected to 5/6 nephrectomy experienced a greater degree of cardiac hypertrophy and downregulation of cardiac sodium potassium ATPase (Na+/K+-ATPase) activity than rats subjected to aortic banding. Moreover, cells isolated from the 5/6 nephrectomy rat hearts displayed impaired contractile function and altered calcium cycling compared with cells isolated from control or aortic constriction rat hearts. The 5/6 nephrectomy rat heart cells displayed a prolonged time constant for calcium recovery following stimulation, which corresponded to decreases in homogenate sarcoplasmic reticulum calcium ATPase-2a (SERCA2a) activity, protein density, and mRNA for SERCA2a. In conclusion, chronic renal failure leads to alterations in cardiac gene expression, which produces alterations in cardiac calcium cycling and contractile function. These changes cannot be explained only by the observed increases in BP. E-mail: [email protected] Copyright © 2003 The Authors. Published by Wolters Kluwer Health, Inc. All rights reserved.