Different Time-course Effects Of Exercise Training On Cardiovascular Function And Cardiac Hypertrophy In Prehypertensive Rats And Its Mechanisms

Objective To investigate the different time-course effects of exercise training on cardiovascular functions, the left ventricular hypertrophy and remodelling in the prehypertensive rats and its mechanisms.Methods Male spontaneously hypertensive rats(SHR) and normotensive Wistar Kyoto rats(WKY) of 5 weeks of age were randomly assigned into sedentary(S) and exercise training(E) group.The trained rats run on a treadmill for 8 and 16 weeks at a moderate intensity(20m/min, 60min/d, 5d/wk). The sedentary control groups were used at the corresponding time-point. Eight groups were divided into At the end of the training protocol, cardiovascular functions(systolic blood pressure, heart rate, cardiac function), the left ventricular hypertrophy and myocardiac fibrosis were evaluated. The m RNA expression of angiotensin converting enzyme(ACE), angiotensin-converting enzyme 2(ACE2), angiotensin? type 1(AT1) receptor and the angiotensin(1-7) receptor(Mas R) in the left ventricle were detected by real-time PCR. The protein levels of ACE, ACE2, AT1 and Mas receptors in the left ventricle were determined with Western blotting.ELISA was used to assay angiotensin ?(Ang?) and angiotensin-(1-7) [Ang-(1-7)] levels in the left ventricle.Results1. Before exercise, systolic blood pressure(SBP)of 5-wk SHR was in the normal level without difference with WKY rats. Eight weeks of exercise training postponed the development of hypertension,delayed the progress of high blood pressure and decreased the resting heart rate(HR). After 8 weeks of exercise training, SBP in the SHR-E group was significantly lower than that of age-matched SHR-S group(155.9 ± 7.2 mm Hg vs. 172.6 ± 8.0 mm Hg, P<0.01), and the HR was also lower than that of the SHR-S group(380 ± 12 beats / min vs. 408 ± 13 beats / min, P <0.05). Sixteen weeks of exercise training delayed the progression of hypertension. After 16 weeks of exercise training, the SHR-E group had significantly lower the SBP and the resting HR than those of the SHR-S group(SBP:170.6 ± 5.9 mm Hg vs. 187.9 ± 6.3 mm Hg,P <0.01; HR:361 ± 14 beats / min vs. 395 ± 12 beats / min, P <0.05). Sixteen of exercise training also decreased the resting HR in the WKY(350 ± 8 beats /min vs. 373 ± 9 beats / min, P <0.05), but had a little effect on the SBP in the WKY.2. Compared with the age-matched WKY-S group, LVEDP was significantly increased in 14 wk SHR-S group(P < 0.01),but-dp / dt max was decreased(P<0.05). Eight weeks of exercise training prevented the abnormal changes of LVEDP and- dp / dt max in the SHR. There were no difference of LVEDP and- dp / dt max between the SHR-E group and the WKY-S group. Sixteen weeks of exercise training further reduced LVEDP(P <0.01) and increased-dp / dt max(P <0.01) in SHR. In addition, sixteen weeks of exercise training also decreased LVEDP in the WKY group(P <0.01), and slightly increased ± dp / dt max, but the change of ± dp / dt max between the WKY-E group and the WKY-S group was not reach a statistical significance.3. Compared with the age-matched WKY-S group, 14 wk SHR-S group of rats showed left ventricular hypertrophy and LVMI was higher than that of WKY-S group(P <0.05). Eight weeks of exercise training prevented the development of left ventricular hypertrophy in the SHR. No significant difference in HW, LVM and LVMI were observed between the SHR-E group and WKY-S group. Afert16 weeks exercise training, left ventricular hypertrophy and interstitial fibrosis were reduced in the SHR-E group. The parameters of HW, LVM, LVMI of the SHR-E group were lower than those of SHR-S group(all, P <0.05). Similarly,both the left ventricular collagen volume fraction(CVF) and perivascular collagen volume fraction(PVCA) were increased in the SHR-E group compared with the SHR-S group(both P <0.05).4. Eight weeks of exercise training slightly enhanced ACE2 m RNA expression(P< 0.05), but decreased ACE m RNA(P < 0.01)and protein expression(P <0.05) in the left ventricle of SHR. Sixteen weeks of exercise training not only upregulated ACE2 m RNA and protein expression( P<0.01) but also downregulated ACE m RNA(P< 0.01)and protein expression(P < 0.05)reduced in the left ventricle of SHR. Also, 16 weeks of exercise upregulated the m RNA and protein expression of Mas receptors(P < 0.01), and downregulated the m RNA and protein expression of AT1 receptors(P < 0.01)in the left ventricle of SHR. However, 16 weeks of exercise did not change the m RNA and protein expression of ACE, ACE2 and AT1 receptors in the left ventricle of WKY, but upregulated the the m RNA and protein expression of Mas receptors.5. The levels of Ang? in the left ventricle were reduced in the SHR subjected to either 8 wk or 16 wk exercise, and only 16 wk exercise elevated the Ang-(1-7)level in the left ventricle of the SHR. Whereas no significant changes of Ang?was found in the left ventricle of WKY afte the same time course of exercise.Conlusions1. Exercise training can postpond the procession of hypertension, reduce high blood pressure, prevent and attenuated the hypertension-induced cardiac hypertrophy and remodelling in the prehypertensive rats.2. Eight weeks of exercise training mainly inhibits the function of ACE-Ang ?-AT1 axis in left ventricle of SHR, whereas 16 wk exercise training decreases the function of ACE-Ang?-AT1 axis and increases the function of ACE2-Ang-(1-7)-Mas axis in the left ventricle of SHR.3. Exercise-based cardiac rehabilitation prevents and improves cardiovascular function and cardiac hypertrophy in the SHR, its mechanisms are partly associated with exercise-induced decrease in blood pressure and regulation of RAS balance in the heart.