Exercise training limits cardiac impairment induced by high-salt diet

Abstract

Purpose: Glucose intolerance is known to be related to diastolic dysfunction. However, its evolution with heart failure progression remains poorly understood. The aim of this study was to examine the evolution of whole body glucose intolerance in relation to cardiac hypertrophy and whether exercise training could reverse the phenotype. Methods: Dahl salt sensitive rats received at the age of 7 weeks either high salt diet (8% NaCl, N=30) or low salt diet (0.3% NaCl, N=18). After 5 weeks diet, half of the animals in each group was subjected to exercise training for 6 weeks (treadmill running at 18m/min, 5% inclination for 60 minutes, 5 days/week). Cardiac function was assessed by echocardiography at baseline, 5 and 11 weeks after the start of the diet. Glucose tolerance was measured using oral glucose tolerance test. Data are shown as mean ± SD. Results: At baseline, body weight, glucose tolerance and cardiac parameters were comparable between the 4 groups. High salt diet induced an overall 40% mortality. After 5 weeks of high salt diet, global cardiac function was preserved but was associated with a significantly reduced diastolic function (E/E'= 15.8±2.3 vs. 13.5±1.7, p<0.05). Hypertrophy in high salt diet was confirmed by an increase in calculated left ventricular mass (+0.20±0.09g compared to +0.08±0.15g, p<0.05). Glucose tolerance was not different between the 2 groups. After 6 weeks exercise training, mortality rate remained comparable within the groups. Cardiac function further worsened in high salt diet as shown by a decrease in fractional shortening (31±9% vs. 38±3% p<0.05). LVEDD and LVESD increased in all groups but this increase was less pronounced with exercise training (data not shown). E/E' increased by 28% with high salt diet, while exercise training limited diastolic dysfunction to a 15% increase. Without reaching statistical significance, the increase of glucose tolerance followed the same trend: the 13% increase with high salt diet was reduced to 6% after exercise training. Exercise training significantly limited increase left ventricular mass (+0.09±0.18 vs. +0.39±0.33), but failed to reduce heart weight/body weight ratio. Conclusions: In summary, our data show that exercise training limits but does not fully reverse cardiac impairment induced by high-salt diet. Evolution of glucose intolerance could not be directly related to changes in cardiac function and to cardiac hypertrophy. It follows from our data that cardiac hypertrophy might not be the triggering factor for glucose intolerance, and that other signaling pathways might be involved in this process.