Portal de Periódicos da CAPES

Coordinated shifts in Na/K-ATPase isoforms and their endogenous ligands during cardiac hypertrophy and failure in NaCl-sensitive hypertension

2004; Lippincott Williams & Wilkins; Volume: 22; Issue: 2 Linguagem: Inglês

10.1097/00004872-200402000-00025

1473-5598

Olga V. Fedorova, Mark I. Talan, Natalia I. Agalakova, Edward G. Lakatta, Alexei Y. Bagrov,

Nitric Oxide and Endothelin Effects

Objectives NaCl loading of Dahl salt-sensitive rats (DS) stimulates marinobufagenin (MBG), an α1 Na/K-ATPase (NKA) isoform ligand. Cardiac function depends on NKA, which is regulated in part by endogenous digitalis-like ligands. Our goal was to study whether changes occur in MBG and endogenous ouabain (EO) production during cardiac remodelling in hypertensive DS, and whether these are associated with changes in myocardial NKA isoforms and sensitivity to MBG and ouabain. Methods Changes in MBG and EO levels, changes in myocardial NKA isoform composition, and sensitivity to endogenous ligands during development of cardiac hypertrophy and the transition to heart failure were studied in DS rats with an 8% NaCl intake. Results The animals developed compensated left ventricular hypertrophy after 4 weeks, which progressed to heart failure at 9–12 weeks. The hypertrophic stage was associated with increased plasma MBG levels (mean ± SEM of 1.22 ± 0.22 versus 0.31 ± 0.03 nmol/l ; P< 0.01), increased sensitivity of NKA to MBG, and an increased abundance of α1 NKA. Plasma levels of EO did not change, and the sensitivity of NKA to ouabain decreased. The transition to heart failure was accompanied by a decrease in α1 NKA, a reduction in plasma MBG, and decreased sensitivity of NKA to MBG. In addition, an increased abundance of ouabain-sensitive α3 NKA, a three-fold rise in plasma EO (1.01 ± 0.13 versus 0.27 ± 0.06 nmol/l), and a seven-fold increase in the ouabain sensitivity of NKA compared with controls were observed. Conclusions During cardiac hypertrophy and the transition to heart failure, a shift in endogenous NKA ligands production is linked to a shift in myocardial NKA isoforms.