The Effect Of Aerobic Exercise On DNA Methylation Of Mas Receptor And RAS System In Mesenteric Artery Of Spontaneously Hypertensive Rats

OBJECTIVE: To investigate the role of aerobic exercise in the regulation of RAS in hypertensive rats and the role of RAS system in the regulation of mesenteric artery function in hypertensive rats.METHODS: The 12-week-old spontaneously hypertensive rat(SHR)and male normotensive control group WKY(Wistar-Kyoto)rats at the same age were selected.They were randomly divided into hypertensive control group(SHR-C),hypertensive exercise group(SHR-E),normotensive control group(WKY-C),normotensive exercise group(WKY-E).The exercise group conducted medium-intensity treadmill training.The tail artery was non-invasively measured for blood pressure.After 12 weeks,the mesenteric artery of each group was used to measure the contractile response of mesenteric artery to angiotensin ? by microvascular tension.The angiotensin peptide was determined by high performance liquid chromatography,including angiotensinogen(Agt),Angiotensin?(Ang?),angiotensin ?(Ang ?);Western blotting observation of angiotensin 1(ACE1),angiotensin 2(ACE2),AT1receptor(AT1R),Mas receptor(MasR)expression;q-RCR assay for Mas receptor mRNA levels;The degree of Mas receptor methylation was determined by bisulfite sequencing PCR.RESULTS: 1)Compared with the WKY-C group,systolic blood pressure,diastolic blood pressure,mean arterial pressure and body weight were significantly increased in the SHR-C group(P<0.05);aerobic exercise reduced the level of systolic blood pressure,diastolic blood pressure,mean arterial pressure and body weight in hypertensive rats(P<0.05).2)Compared with the WKY-C group,the degree of contraction induced by Ang? of the mesenteric artery was significantly increased in the SHR-C group(P<0.05);compared with the SHR-C group,the contractile response of the mesenteric artery to the Ang? in the SHR-E group was significantly down-regulated.(P<0.05).3)Compared with the WKY-C group,the levels of Agt,AngI and Ang ? in the plasma of the SHR-C group were significantly increased(P<0.05);the aerobic exercise induced the content of Ang?,Ang? in the plasma of hypertensive rats significantly(P<0.05).4)Compared with the WKY-C group,theexpression of ACE1,AT1 R,ACE2,and MasR protein in the mesenteric artery of SHR-C group was significantly up-regulated(P<0.05);compared with SHR-C group,the expression of ACE1,AT1 R,ACE2 and MasR protein of mesenteric artery in SHR-E group was significantly down-regulated(P<0.05).Compared with the WKY-C group,the ratio of ACE2/ACE1 and MasR/AT1 R in the SHR-C group was significantly lower(P<0.05);compared with the SHR-C group,the ratio of ACE2/ACE1 and MasR/AT1 R was significantly increased(P< 0.05).5)Compared with the WKY-C group,the Mas receptor mRNA level of the SHR-C group was significantly up-regulated(P<0.05).Aerobic exercise significantly down-regulated the Mas receptor mRNA level in hypertensive rats(P<0.05).6)Compared with the WKY-C group,the Mas1 gene promoter region of the SHR-C group showed significant demethylation(P<0.05),while the methylation degree of the hypertensive exercise group was significantly increased(P< 0.05).CONCLUSION: Aerobic exercise can effectively reduce the level of angiotensins in plasma,and reduce the expression of RAS system contractile axis and diastolic axis key invertases ACE1,ACE2 and receptors AT1 R and MasR in mesenteric artery of hypertensive rats.At the mean time,aerobic exercise regulates the balance between ACE1-AT1 R and ACE2-MasR in the mesenteric artery of hypertensive rats,and increases the ratio of diastolic axis in the mesenteric artery of hypertensive rats.MasR hypermethylation in the promoter region may be one of the causes of the diastolic axis of motor regulation.