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
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.