The Mechanism Of Exercise Training Regulating Spontaneous Hypertension Through RhoA/ROCK Signaling Pathway

Objective:Hypertension is a global common disea se and multiple disease caused by genetic and social environment and is a major risk factor for heart failure,myocardial infarction,cerebrovascular disease and other common chronic diseases.The survey results show that the prevalence of hypertension in China is rising year by year,which brings a heavy economic burden to the whole family and economic and social development.Therefore,the prevention and treatment of hypertension is one of the main tasks of clinical workers.At present many research results show that Ex T have been able to effectively improve chronic onset age and hypertension various abnormal physiological regulation of disease of heart head blood-vessel,improve the quality of daily life of patients with high pressure,to improve prognosi s and reduce the patient’s high-pressure cardio-cerebral mortality,however the specific mechanism is not fully clear.In this study,we investigated the mechanism of exercise training regulating blood pressure in spontaneously hypertensive rats through Rh o A/ROCK signaling pathway.Methods:(1)According to the principle of randomization,the rats were divided into six groups(8rats in each group,n=8): WKY Sedentary control group(WKY-Sedentary,WKY-Sed),WKY Exercise Training group(WKY-Ex T),SHR-Sedentary control group(SHR-Sedentary,SHR-Sed),SHR-Exercise Training group(SHR-Ex T),SHR-Fasudil group(SHR-Fasudil)SHR-Ex T-LPA group(SHR-Ex T-LPA).(2)Blood pressure(BP)was monitored by non-invasive computerized caudal artery pressure monitoring system at the age of 8 weeks(before exercise training),and then the BP was measured once a week.After 12 weeks of exercise training,the changes of Blood pressure and body weight were observed in each group.(3)After 12 weeks of exercise training,the expression activities of RhoA,ROCK and MLCP in myocardial tissue of rats in WKY and SHR groups were determined by Western blot.(3)After 12 weeks of exercise training,the m RNA expression levels of RhoA,ROCK and MLCP gene in myocardial tissue of rats in each group were detected by RT-PCR.Results:(1)Before Ex T(8 weeks of age),the basal systolic blood pressure in SHR-Sed group was significantly higher than that in WKY-Sed group,and the difference between the two groups increased gradually with the increase of week of age.Compared with shr-sed group,BP in SHR-Ex T group and SHR-Fasudil group was significantly decreased after 12 weeks of exercise(P<0.05).BP in SHR-Ex T group was lower than that in SHR-Ex T-LPA group.However,Ex T had no significant effect on BP in WKY g roup(P>0.05).(2)The effects of Ex T on m RNA and protein expressions of RhoA and ROCK in myocardium of rats in each group: after 12 weeks of exercise training,compared with WKY-Sed group,the expression activities of RhoA and ROCK in WKY-Ex T group were decreased(P<0.05),while the expression levels of RhoA and ROCK in SHR-Sed group were significantly higher(P<0.05).Compared with shr-sed group,the expression levels of RhoA and ROCK in myocardium of SHR-Ex T group and SHR-Fasudil group were significantly decreased(P < 0.05).Compared with SHR-Ex T group,the relative expression of ROCK protein in SHR-Ex T-LPA group was increased(P < 0.05).(3)Ex T analysis on the expression level of MLCP downstream of RhoA/ROCK signaling pathway in myocardium of rats in each group: Compared with WKY-Sed group,MLCP m RNA and protein expression levels in WKY-Ex T group were increased,but there was no statistical difference(P>0.05),while MLCP m RNA and protein expression levels in SHR-Sed group were significantly decreased,showing statistical difference(P<0.05).Compared with SHR-Sed group,the expression levels of MLCP m RNA and protein in SHR-Ex T groupand SHR-Fasudil group were increased,(P<0.05).Compared with SHR-Ex T group,MLCP m RNA and protein expression levels in SHR-Ex T-LPA group were decreased(P< 0.05).Conclusion:(1)Moderate and low intensity exercise training and injection of Rho kinase inhibitors could significantly reduce blood pressure in SHR rats,and induce changes in m RNA and protein expression levels of RhoA,ROCK and MLCP(2)Exercise training may increase the m RNA and protein levels of MLCP by inhibiting the activities of RhoA and ROCK,key factors of RhoA/ROCK chemical signal transduction pathway,and decrease the blood pressure level of spontaneously hypertensive rats.(3)After moderate and low intensity exercise training,SHR rats were injected with Rho kinase agitator,and blood pressure level increased,which to some extent counteracts the hypotensive effect of exercise training,suggesting that RhoA/ROCK signal transduction pathway may be involved in exercise training to improve blood pressure regulation in spontaneously hypertensive rats.