| Full text | |
| Author(s): |
Rolim, Natale P. L.
;
Medeiros, Alessandra
;
Rosa, Kaleizu T.
;
Mattos, Katt C.
;
Irigoyen, Maria C.
;
Krieger, Eduardo M.
;
Krieger, Jose E.
;
Negrão, Carlos E.
[8]
;
Brum, Patricia C.
Total Authors: 9
|
| Document type: | Journal article |
| Source: | Physiological Genomics; v. 29, n. 3, p. 246-252, May 2007. |
| Field of knowledge: | Health Sciences - Medicine |
| Abstract | |
The molecular basis of the beneficial effects associated with exercise training (ET) on overall ventricular function (VF) in heart failure (HF) remains unclear. We investigated potential Ca2+ handling abnormalities and whether ET would improve VF of mice lacking 2A- and 2C-adrenoceptors (2A/2CARKO) that have sympathetic hyperactivity-induced HF. A cohort of male wild-type (WT) and congenic 2A/2CARKO mice in a C57BL/J genetic background (5-7 mo of age) was randomly assigned into untrained and trained groups. VF was assessed by two-dimensional guided M-mode echocardiography. Cardiac myocyte width and ventricular fibrosis were evaluated with a computer-assisted morphometric system. Sarcoplasmic reticulum Ca2+ ATPase (SERCA2), phospholamban (PLN), phospho-Ser16-PLN, phospho-Thr17-PLN, phosphatase 1 (PP1), and Na+-Ca2+ exchanger (NCX) were analyzed by Western blotting. ET consisted of 8-wk running sessions of 60 min, 5 days/wk. 2A/2CARKO mice displayed exercise intolerance, systolic dysfunction, increased cardiac myocyte width, and ventricular fibrosis paralleled by decreased SERCA2 and increased NCX expression levels. ET in 2A/2CARKO mice improved exercise tolerance and systolic function. ET slightly reduced cardiac myocyte width, but unchanged ventricular fibrosis in 2A/2CARKO mice. ET significantly increased the expression of SERCA2 (20%) and phospho-Ser16-PLN (63%), phospho-Thr17-PLN (211%) in 2A/2CARKO mice. Furthermore, ET restored NCX and PP1 expression in 2A/2CARKO to untrained WT mice levels. Thus, we provide evidence that Ca2+ handling is impaired in this HF model and that overall VF improved upon ET, which was associated to changes in the net balance of cardiac Ca2+ handling proteins. (AU) | |