Eeffect Of Aerobic Exercise Combimed With Oyster Peptide On SHR Blood Pressure And Its Relationship With Arginine Metabolism

Objective:(1)To explore the effects of aerobic exercise and oyster peptide(OP)interventions on SHR blood pressure and their interaction effects.(2)To explore the physiological mechanisms of aerobic exercise and OP intervention in SHR blood pressure in terms of L-Arg metabolism and its L-Arg-eNOS-NO pathway.Method:Five-week-old SPF-rated male WKY rats were randomly divided as normal control(WC,n=10)and 40 spontaneously hypertensive rats(SHR)into SHR control group(SC,n=10),SHR aerobic exercise intervention group(SE,n=10),SHROP intervention group(SOP,n=10),SHR+aerobic exercise+OP intervention group(SEOP,n=10).No exercise was performed in the WC,SC and SOP groups,while the rats in the SE and SEOP groups underwent 60 min weightless swimming training every afternoon,6 times/week,and the SOP and SEOP groups received oyster peptide solution at a dose of 1.2 g/Kg body weight every morning.After 8 weeks,all the indicators were tested,including serum levels of Angiotensin Ⅱ(Ang Ⅱ),Angiotensin 1-7(Angl-7),Endothelin-1(ET-1),Nitric Oxide(NO)and Endothelial Nitric Oxide Synthase(eNOS)in the aorta,Arginine(L-Arg),Asymmetric Dimethylarginine(ADMA)and L-Citrulline(L-Cit)and Angiotensin-Converting Enzyme 2(ACE2)protein expression levels,Protein Arginine Methyltransferase-1(PRMT-1)and Dimethylarginine Dimethylamine Hydrolase(DDAH-2)mRNA and protein expression levels.Result:(1)Compared with WC group,the systolic blood pressure(SBP)and diastolic blood pressure(DBP)in SC group were significantly increased(P=0.000,P=0.000);SBP and DBP were significantly decreased in the SOP and SE groups compared with the SC group(P=0.000,P=0.000),while SBP and DBP were not significantly changed in the SEOP group compared with the SE group(P=0.660,P=0.806).(2)Compared with WC group,the contents of cardiac ACE2 protein and serum Angl-7 in SC group were significantly decreased(P=0.000,P=0.000),while the content of serum Ang Ⅱ was significantly increased(P=0.000).Compared with SC group,ACE2 protein level was not significantly increased in SE group(P=0.060),ACE2 protein level was significantly increased in both SOP and SEOP groups(P=0.022,P=0.012),serum Ang Ⅱ content was significantly decreased(P=0.000,P=0.000,P=0.000),only serum Ang1-7 content was significantly increased in SOP group(P=0.002).Compared with SE group,myocardial ACE2 protein level and serum Ang1-7 content were further increased in SEOP group,and serum Ang Ⅱ content was further decreased,but there were no significant differences(P=0.51,P=0.192,P=0.225)(3)Compared with WC group,aorta eNOS content in SC group was significantly decreased(P=0.000),serum NO content was significantly decreased(P=0.000),but serum ET-1 content was not significantly increased(P=0.0457).Compared with the SC group,the eNOS content in the aorta of the SOP group was not significantly increased(P=0.058),but the eNOS content in the aorta of the SE and SEOP groups was significantly increased(P=0.001,P=0.000).Serum NO content in SE,SOP and SEOP groups was significantly increased(P=0.002,P=0.000,P=0.000);Although there was no significant decrease in serum ET-1 content in SE group(P=0.576),there was a significant decrease in serum ET-1 content in SOP and SEOP groups(P=0.007,P=0.001).Compared with the SE group,although the aortic eNOS content was not further significantly increased(P=0.139),the serum NO content was further significantly increased(P=0.01),and the serum ET-1 content was further significantly decreased(P=0.003)(4)Compared with WC,the mRNA expression of PRMT-1 and DDAH-2 in SC group was significantly up-regulated(P=0.000,P=0.033),the protein of PRMT-1 was significantly increased(P=0.000),and the protein of DDAH-2 was significantly decreased(P=0.000).The contents of L-Arg and L-Cit in myocardium were significantly decreased(P=0.029,P=0.045),and the content of ADMA was significantly increased(P=0.019).Compared with SC group,the mRNA and protein expressions of PRMT-1 in SE,SOP and SEOP groups were significantly decreased(P=0.000),and the mRNA and protein expressions of DDAH-2 were significantly increased(P=0.000,P=0.000,P=0.000,P=0.044,P=0.041,P=0.001).The contents of L-Arg and L-Cit in myocardium in SE,SOP and SEOP groups were significantly increased(P=0.005,P=0.021,P=0.000;P=0.001,P=0.000,P=0.000),and the contents of ADMA were significantly decreased(P=0.000),except that L-Cit content in SEOP group was not significantly increased(P<0.05).Compared with SE group,PRMT-1 mRNA expression and ADMA content in myocardium of SEOP group were not significantly decreased(P=0.307,P=0.441),while PRMT-1 protein expression was significantly decreased(P=0.007),myocardial DDAH-2 mRNA expression was significantly increased(P=0.000),while DDAH-2 protein and L-Arg content were not significantly increased(P=0.144,P=0.067),but myocardial L-Cit content was significantly decreased(P=0.016).Conclusion:(1)Long-term aerobic exercise and oyster peptide supplementation can significantly reduce the SBP and DBP of SHR and have significant hypotensive effect,but aerobic exercise combined with oyster peptide does not seem to have better hypotensive effect.(2)Aerobic exercise and oyster peptide supplementation can increase the expression of ACE2 in SHR myocardium,promote the decomposition of Ang Ⅱ,and cause the decrease of serum Ang Ⅱ content.To a certain extent,aerobic exercise combined with oyster peptide supplementation has a better effect on improving the Ang Ⅱ-ACE2-Angl-7 pathway than aerobic exercise alone,which is one of the physiological mechanisms of aerobic exercise and oyster peptide lowering blood pressure.(3)Aerobic exercise and oyster peptide supplementation can improve the function of SHR endothelial cells,promote the synthesis of NO,and inhibit the secretion of ET-1,so as to effectively improve the endothelial cell-mediated vasodilation effect,which may also be an important physiological mechanism of aerobic exercise and oyster peptide supplementation to reduce SHR blood pressure.The effect of aerobic exercise combined with oyster peptide supplementation on improving endothelial cell function was significantly better than that of aerobic exercise alone.(4)Aerobic exercise and supplement the oyster peptide,on the one hand,can significantly improve the SHR myocardial L-Arg content.On the other hand,it can effectively improve the myocardial PRMT-1-ADMA-DDAH-2pathways,effectively reduce the generation of ADMA,increase the activity of the eNOS.This is the biological mechanism by which aerobic exercise and oyster peptide supplementation improve the SHR L-Arg-Enos-NO pathway To a certain extent,aerobic exercise combined suWpply oyster peptide improve myocardial PRMT-1-ADMA-DDAH-2 channel better than pure aerobic exercise.