High salt intake accelerated cardiac remodeling in spontaneously hypertensive rats: time window of left ventricular functional transition and its relation to salt-loading doses.

Salt-loading is an accelerator of hypertensive left ventricular (LV) remodeling. The relationship between salt-loading doses and the time window in which a transition from compensated to decompensated LV hypertrophy occurs in spontaneously hypertensive rats (SHR) is unclear. Eight-week-old male SHR and Wistar Kyoto rats (WKY) were randomized to receive normal (0.5% NaCl) and high salt diets (4% or 8% NaCl) for 12 weeks. Left ventricular remodeling was dynamically determined by echocardiography. LV invasive hemodynamics and morphologic staining [collagen deposition, cardiomyocte hypertrophy, DNA damage (8-hydroxy-2-deoxyguanosine, 8-OHdG) and apoptosis] were performed at time of sacrifice. Cardiac malonyldialdehyde (MDA) level was measured by ELISA. No differences between 4% and 8% salt diets, in terms of blood pressure (BP) levels, heart mass index, and myocardial fibrosis were observed either in SHR or in WKY. In high salt-loaded SHR, the LV ejection fraction and wall thickness peaked at 8 weeks after salt-loading, parallel with a progressive enlargement of the LV chamber size. Furthermore, when compared to 4% salt SHR, LV functions were significantly compromised in 8% salt SHR, accompanied by more prominent cardiomyoctye hypertrophy, oxidative stress (and related DNA damage), and apoptosis. Salt-loading for 12 weeks with 8% NaCl diet is more efficient to induce LV dysfunction than 4% NaCl diet does in SHR, possibly by initiating increased oxidative stress and resultant cardiac damage. Moreover, 8 to 12 weeks after 8% salt-loading is the key time window in which a transition from compensated to decompensated LV hypertrophy occurs.