| Objective:Along with the people life extension,elderly people are gradually increasing in popμlation proportion.Hypertension is one of the most common cardiovascμlar diseases,harms the people's health most,its prevalence grows along with aging.At present,endothelium-nitrogen monoxide (NO)-oxidation stress chain is reported to play an important role in hypertension occurrence and development in the non-haemodynamics mechanism.This experiment is proposed to observe the blood pressure(BP)and variability monitored by radiotelemetric technique(RTT)in conscious unrestrained spontaneous hypertensive rats;To observe the endothelium function and oxidation stress in SHR with different age;To investigate the responsibility to antihypertensive drug of SHR with different age;To investigate the level changes of glutathione S-transferase mu type 1(Gstm1)in SHR with different age by western-blot technique,and its possible relationship with blood vessel endothelium and oxidation stress;To provide a new target for antihypertensive drug.Method and Resμlts:1.Research on ambμlatory blood pressure changes and morphology of resistance vessel of SHR with different age16 week and 40 week aged SHR models were established,the blood pressure(BP)were monitored by radiotelemetric technique(RTT).The data of BP,diurnal variation and the variability were analyzed.The resμlts showed that night blood pressure fall rate in 16 weeks group was higher than in 40 weeks group(0.0498%vs 0.0211%,P＜0.05),blood pressure variability in 40 weeks group was higher than in 16 weeks group.Tunica media areae/lumen area ratio of arteria mesenterica was increased with aging(0.8955±0.10,1.0653±0.15 vs 1.3373±0.19,P＜0.05).2.The endothelium function and oxidation stress in SHR with different ageEndothelium-dependent vasodilation of exsomatized aorta thoracalis and renal artery in 5 week,16 week and 40 week aged SHR were observed and compared.Radio-immunity(RI) method,nitrate reductase method,thio- barbituric acid(TBA)method;dipl-nitrobenzene method were used to measure the levels of endothelin(ET),NO,MDA and the GPx;GSTM1 protein expression in the aorta of 40 week SHR was measured by western-blot.The resμlts indicated that,the endothelium-dependent vasodilation function is weakened along with aging.Vasoactive substance such as NO/ET and the oxidized stress symbolized GPx, MDA were changing along with aging,serum NO level in 16 and 40 week SHR were lower than that in 5 week SHR(12.84±1.58μmol/L,12.17±1.17μmol/L vs 22.64±1.69μmol/L,P＜0.01); No significant difference was found in ET level among the three groups;levels of MDA (13.71±1.47pg/ml)in 40 week were significant higher than in 5week SHR(7.54±1.19 pg/ml) and 16 week SHR(7.94±0.83 pg/ml,P＜0.01);GSH-Px activity(2368±60.39U/ml)in 40 week were significant lower than in 5week SHR(2925±75.11 U/ml)and 16 week SHR(2976±329.94 U/ml,P＜0.01);the aorta Gstml expression in 40 week SHR was decreased than the other groups(716.93±133.72 vs 1215.52±270.35,P＜0.05).3.Effect of taurine combined with metoprolol treatment on blood pressure reactivity and resistance vessel morphology of SHRThe 24 h BP of the 16 and 40 week SHR treated by metoprolol(Met),taurine(Tau)and Met +Tau combination treatment for 14 days were monitored by using digital spotfilm imaging(DSI) remote sensing monitoring system.And the blood pressure reactivity and resistance vessel morphology changes were observed.The resμlts showed that,at the 1,7 and 14 days after treatment,the 24 h dynamic BP and the BP load in combination treatment group were significantly lower than those in taurine treatment group and metoprolol treatment group.The coefficient variation of BP(BPVC)was higher and the smoothness index was lower in metoprolol treatment group,when compared with those of the combination treatment goup.The tunica media areae/lumen area ratio was improved in 16 week SHR after treatment than the control group(0.7627±0.12,0.8110±0.15,0.7138±10.12 vs 1.0653±0.15,P＜0.01).4.Effect of combination treatment on endothelium function and oxidation stress in SHR with different ageEndothelium-dependent vasodilation of exsomatized aorta thoracalis and renal artery in 5 week,16 week and 40 week aged SHR treated by metoprolol(Met),taurine(Tau)and Met+Tau combination treatment were observed and compared.The levels of endothelin(ET),NO,MDA and GPx were measured;GSTM1 protein expression in the aorta of 40 week SHR after Tau treatment was measured by western-blot.The resμlts indicated that,the treatment did not improve the endothelium function and oxidation stress in 5 week SHR,especially in Tau treatment group(62.14±14.68%vs 78.88±11.04%,P＜0.01).Endothelium-dependent vasodilation in 16 week SHR was improved, NO/ET and GSH-Px,MDA levels were accordingly increased or decreased,especially in Met+Tau group.And it was not significant in 40 week SHR after treatment for 14 days.But GSH-Px activity(3052.80±283.66U/ml vs 2368.00±60.39U/ml,P＜0.01),GSTM1 were increased in Tau group than in control group,and MDA level was decrease(9.45±0.66pg/ml vs 13.71±1.47pg/ml,P＜0.01).Conclusions1.24h blood pressure variability in 40 week SHR is more than in 16 week SHR;Also along with week age increase,resistance blood vessel(arteria mesenterica)tunica media vasorum area/lumen area increase.Tunica media areae/lumen area ratio of arteria mesenterica is increasing with aging.2.The damaged endothelium function and increased oxidation stress are existed in SHR and are aggratated with aging.3.Effect of Met,Tau and Met+Tau treatment cannot improve on endothelium function and oxidation stressing in 5 week SHR,and have no effect on mesenteric artery resistance vessel morphology.4.Met+Tau can improve the levels of vasoactive substance and endothelium function in 16 week SHR,significant decrease the blood pressure,the effect is lasting and steady,and decrease the tunica media area/lumen area ratio at the same time.5.Tau and Met+Tau can effectively prevent the blood pressure increasing,Tau can significantly improve the oxidation stress and decrease the tunica media area/lumen area ratio.
|
PDF Full Text Request