UT-A Urea Transporter Protein in Heart: Increased Abundance During Uremia, Hypertension, and Heart Failure

R. Duchesne, J. D. Klein, J. B. Velotta, J. J. Doran, P. Rouillard, B. R. Roberts, A. A. McDonough, J. M. Sands
2001 Circulation Research  
Urea transporters have been cloned from kidney medulla (UT-A) and erythrocytes (UT-B). We determined whether UT-A proteins could be detected in heart and whether their abundance was altered by uremia or hypertension or in human heart failure. In normal rat heart, bands were detected at 56, 51, and 39 kDa. In uremic rats, the abundance of the 56-kDa protein increased 1.9-fold compared with pair-fed, sham-operated rats, whereas the 51-and 39-kDa proteins were unchanged. We also detected UT-A2
more » ... detected UT-A2 mRNA in hearts from control and uremic rats. Because uremia is accompanied by hypertension, the effects of hypertension per se were studied in uninephrectomized deoxycorticosterone acetate salt-treated rats, where the abundance of the 56-kDa protein increased 2-fold versus controls, and in angiotensin II-infused rats, where the abundance of the 56 kDa protein increased 1.8-fold versus controls. The 51-and 39-kDa proteins were unchanged in both hypertensive models. In human left ventricle myocardium, UT-A proteins were detected at 97, 56, and 51 kDa. In failing left ventricle (taken at transplant, New York Heart Association class IV), the abundance of the 56-kDa protein increased 1.4-fold, and the 51-kDa protein increased 4.3-fold versus nonfailing left ventricle (donor hearts). We conclude that (1) multiple UT-A proteins are detected in rat and human heart; (2) the 56-kDa protein is upregulated in rat heart in uremia or models of hypertension; and (3) the rat results can be extended to human heart, where 56-and 51-kDa proteins are increased during heart failure. (Circ Res. 2001;89:139-145.) Key Words: urea Ⅲ cardiac hypertrophy Ⅲ polyamine Ⅲ human heart failure Ⅲ rat models Materials and Methods Animal Models Animal protocols were approved by the Emory Institutional Animal Care and Use Committee. Sprague-Dawley rats (National Cancer Institute, Frederick, Md) were anesthetized using intraperitoneal ketamine (Fort Dodge Laboratories) and xylazine (Miles Agricultural Division). For the uremia model, rats underwent a 5/6 nephrectomy, were fed 40% protein, and drank 1 ⁄4 normal saline. 16,26 -28 Control rats underwent sham operation and were pair-fed. For the Original
doi:10.1161/hh1401.093293 pmid:11463720 fatcat:nnjjtyjfsnhdni2hqfnj4scpdm