Fedorova Olga V, Talan Mark I, Agalakova Natalia I, Lakatta Edward G, Bagrov Alexei Y
Laboratory of Cardiovascular Science, Intramural Research Program, National Institute on Aging, NIH, Baltimore, Maryland 21224, USA.
J Hypertens. 2004 Feb;22(2):389-97. doi: 10.1097/00004872-200402000-00025.
NaCl loading of Dahl salt-sensitive rats (DS) stimulates marinobufagenin (MBG), an alpha1 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.
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.
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 alpha1 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 alpha1 NKA, a reduction in plasma MBG, and decreased sensitivity of NKA to MBG. In addition, an increased abundance of ouabain-sensitive alpha3 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.
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.
给 Dahl 盐敏感大鼠（DS）喂食氯化钠会刺激海蟾蜍精（MBG），它是α1 钠钾 ATP 酶（NKA）同工型的配体。心脏功能依赖于 NKA，而 NKA 部分受内源性类洋地黄配体调节。我们的目标是研究在高血压 DS 大鼠心脏重塑过程中，MBG 和内源性哇巴因（EO）的产生是否发生变化，以及这些变化是否与心肌 NKA 同工型的变化以及对 MBG 和哇巴因的敏感性相关。
在摄入 8%氯化钠的 DS 大鼠中，研究心脏肥大发展过程中以及向心力衰竭转变过程中 MBG 和 EO 水平的变化、心肌 NKA 同工型组成的变化以及对内源性配体的敏感性。
动物在 4 周后出现代偿性左心室肥大，并在 9 - 12 周进展为心力衰竭。肥大阶段与血浆 MBG 水平升高（平均值±标准误为 1.22±0.22 对 0.31±0.03 nmol/l；P < 0.01）、NKA 对 MBG 的敏感性增加以及α1 NKA 丰度增加有关。血浆 EO 水平未发生变化，NKA 对哇巴因的敏感性降低。向心力衰竭的转变伴随着α1 NKA 的减少、血浆 MBG 的降低以及 NKA 对 MBG 的敏感性降低。此外，观察到哇巴因敏感的α3 NKA 丰度增加、血浆 EO 升高三倍（1.01±0.13 对 0.27±0.06 nmol/l），且与对照组相比 NKA 对哇巴因的敏感性增加了七倍。
在心脏肥大和向心力衰竭转变过程中，内源性 NKA 配体产生的变化与心肌 NKA 同工型的变化相关。
