运动训练激活中枢ACE2-Ang(1-7)-MAS轴延缓高血压进展

Exercise training attenuates hypertension progression via activation of central ACE2-Ang( 1-7)-Mas axis in prehypertensive rats

目的:观察运动训练对高血压前期的血压进展、血压调节以及中枢血管紧张素转换酶2(ACE2)-血管紧张素(Ang)(1-7)-MAS轴的影响,探讨运动训练延缓高血压进展的中枢机制。方法:5周龄雄性自发性高血压大鼠(SHR)和正常血压WKY大鼠各20只,随机分成安静组和运动训练组,每组10只。运动组大鼠进行20周中低强度跑台运动。采用尾套法测定大鼠尾动脉收缩压,药物法检测动脉压力反射敏感性(BRS)。Real-time PCR和Western blot分别检测压力反射中枢ACE2和MAS的mRNA和蛋白表达。侧脑室注射MAS受体激动剂Ang(1-7)及拮抗剂A779,检测注药前后的BRS变化。结果:始于高血压前期的运动训练可推迟高血压发生、延缓高血压进展,明显降低SHR和WKY大鼠血压(P<0.05),并改善SHR血压调节功能,提高其BRS(P<0.01);此处,运动训练可上调SHR压力反射中枢(孤束核、延髓头端腹外侧区和室旁核中)ACE2和MAS的mRNA和蛋白表达(P<0.05);中枢给予A779抵消了运动对SHR BRS的改善作用(P<0.01),相反,注射Ang(1-7)则增强安静组和运动组SHR的BRS(P<0.05)。结论:运动训练延缓高血压前期进展到高血压的进程及改善血压调节作用可能与运动增强中枢ACE2-Ang(1-7)-MAS轴功能有关。

AIM:To investigate the effects of exercise training on the progression from prehypertension to hypertension,blood pressure regulation and the angiotensin-converting enzyme2(ACE2)-angiotensin(Ang)(1-7)-MAS axis activation in cardiovascular centers,and to elucidate the central mechanisms of exercise training postponing hypertension progression.METHODS:The male spontaneously hypertensive rats(SHR;n=20,5weeks old)and normotensive Wistar Kyoto(WKY)rats(n=20)were randomly assigned to sedentary(Sed)group and exercise training(ExT)group.The trained rats run on a treadmill in moderate-intensity for20weeks.Systolic blood pressure(SBP)was measured by tail-cuff method.The baroreflex sensitivity(BRS)was assessed by intravenous injection of phenylephrine.The expression of ACE2and MAS receptor at mRNA and protein levels in baroreflex centers were determined by real-time PCR and Western blot,respectively.Alterations of BRS were evaluated before and after intracerebroventricular injection of MAS receptor agonist Ang(1-7)and its antagonist A779,respectively.RESULTS:Compared with SHR+Sed group,exercise training since prehypertension significantly postponed the development of hypertension,delayed the hypertension progression,and decreased SBP in both SHR and WKY rats(P<0.05).Exercise training enhanced blood pressure regulation and improved the BRS in SHR(P<0.01).The expression of ACE2and MAS receptor at mRNA and protein levels in the baroreflex centers(rostral ventrolateral medulla,nucleus tract solitarius and paraventricular nucleus)were up-regulated in SHR+ExT group(P<0.05).Central administration of A779abolished the benefits of exercise-induced improvement of BRS in SHR+ExT group(P<0.01).In contrast,Ang(1-7)improved the BRS in both SHR+Sed group and SHR+ExT group(P<0.05).CONCLUSION:Exercise training postpones hypertension progression and improves blood pressure regulation,which may be associated with the activation of central ACE2-Ang(1-7)-Mas axis.