Long-term Exercise Training Alleviates Hypertension Progress And Its Central Mechanisms In The Prehypertensive Rats

Objective:To investigate the effects of long-term exercise training on the progress of blood pressure,the regulation of blood pressure and m RNA and protein expression of angiotensin converting enzyme(ACE),angiotensin converting enzyme 2(ACE2),angiotensin Ⅱ type-1 receptors(AT1)and angiotensin-(1-7)receptors(MAS)in the cardiovascular centers of the prehypertensive rats and its mechanisms.Methods : Five week old male spontaneously hypertensive rats(SHR)and normotensive Wistar Kyoto rats(WKY)were randomly assigned to the sedentary(Sed)or the exercise training(Ex T)group,n=20 rats for each group.The trained rats run on a treadmill in the moderate-intensity for a period of 20 weeks(20m/min,60min/d,5d/wk).The sedentary rats were used to be the control at the corresponding time-point.Systolic blood pressure(SBP)and heart rate(HR)were measured by a tail-cuff method.The baroreflex function was assessed by intravenous injection of phenylephrine.Baroreflex sensitivity(BRS)was calculated by the ratio of HR responses/MAP changes before and after phenylephrine administrations.The m RNA and protein expression of ACE,ACE2,AT1 and MAS in the cardiovascular centers were detected by real-time PCR and Western blot.To investigate the effects of central ACE-Ang Ⅱ-AT1 pathway and ACE2-Ang(1-7)-MAS pathway on the regulation of blood pressure and benefits that exercise training postponed hypertension progress,Ang Ⅱ and Ang(1-7)as well as their antagonists were microinjected into the lateral ventricle,respectively,to evaluate the alteration of BRS.Results:1.SHR developed hypertension at the age of 8 weeks in the SHR+Sed group and of 10 weeks in the SHR+Ex T group,which SBP was 146.6 ± 4.5 mm Hg and148.2 ± 8.1 mm Hg,respectively.After 20 wk period of exercise,SBP of the SHR+Ex T group was reduced by 16.7mm Hg compared with that of the SHR +Sed group(176.1±8.1 vs.192.8±8.3mm Hg,P < 0.01).Similarly,exercise training resulted in significantly the reduction of SBP in WKY+Ex T rats when compared with WKY+Sed rats(117.6±5.7 mm Hg vs.125.4±3.7mm Hg,P<0.05).Exercise training also decreased HR both in the SHR+Ex T rats(375±11 vs.390±9bpm,P<0.05)and the WKY+Ex T rats(350±9 vs.362±9 bpm,P<0.05)when compared to their sedentary groups.2.Twenty weeks of exercise training improved the regulation of blood pressure and the blunted BRS in the SHR+Ex T rats.It was observed that SHR+Ex T rats exhibited marked increases in BRS compared to SHR+Sed rats(1.6±0.1 vs.0.7±0.1 bpm/mm Hg P<0.01),however,it was also lower than that of WKY +Sed group(P < 0.05).In addition,exercise training enhanced the regulation of blood pressure on WKY rats,WKY+Ex T rats showed a slightly increase in BRS compared with WKY+Sed rats,but the difference between WKY+Ex T and WKY+Sed rats had no statistical significance.3.Intracerebroventricular(ICV)Injection of Ang Ⅱ decreased the BRS in both SHR+Sed and SHR+Ex T rats,and also abolished the benefits of exercise-induced improvement of the BRS in the SHR+Ex T group.On the contrary,central administration of Losartan enhanced the BRS in both of the SHR+Sed and the SHR +Ex T groups,and BRS was normalized in SHR+Ex T groups.4.ICV injection of A779 abolished the benefits that exercise-induced improvement of BRS in the SHR+Ex T rats,but it had no influence in SHR+Sed rats.In contrast,ICV injection of Ang(1-7)improved the BRS in both of the SHR+Sed and the SHR +Ex T groups.5.It was found that m RNA and protein expression of ACE and AT1 receptor in cardiovascular center [rostral ventrolateral medulla(RVLM),nucleus tract solitarius(NTS),paraventricular nucleus(PVN)] was inhibited following 20 weeksexercise in SHR,P<0.05 or P<0.01,in contrast,m RNA and protein expression of ACE2 and Mas receptor was elevated in SHR,P<0.05 or P<0.01.Conclusions:1.Long-term exercise training reduces high blood pressure,enhances blood pressure regulation,and postpones the progress of hypertension.2.Treatment of AT1 and MAS receptor agonists and antagonists in the cardiovascular centers changes the benefits of exercise training on blood pressure regulation,indicating that the central rennin-angiotensin system mediates this procession.3.Long-term exercise training downregulates the expression of ACE and AT1,and upregulates the expression of ACE2 and MAS in the cardiovascular centers,indicating that the alterations of central ACE-Ang II-AT1 axis and ACE2-Ang-(1-7)-MAS axis induced by exercise training may be responsible for the postpone of hypertension progress.