| 204 | 3 | 33 |
| 下载次数 | 被引频次 | 阅读次数 |
目的:研究不同运动强度对自发性高血压大鼠(SHR)的肠系膜动脉的大电导钙激活钾通道(MaxiK)功能重塑的影响。方法:54只3月龄雄性SHR随机分为3组:低强度有氧运动组(SHR-L,n=18),中强度有氧运动组(SHR-M,n=18)和安静组(SHR,n=18)。18只同龄雄性WKY作为空白对照组(WKY,n=18),运动组完成8周的运动训练。运动方案:坡度0°,60 min/d,5 d/w,SHR-L,14 m/min,40%~49%VO2max;SHR-M,20 m/min,55%~65% VO2max。8周运动结束后急性酶分离肠系膜动脉平滑肌细胞(VSMCs)。记录不同运动强度对肠系膜动脉MaxiK通道电流及通道蛋白亚基表达的影响。结果:1.运动训练前,与WKY组相比,SHR安静组体重(BW)无显著性差异(P>0.05),但心率(HR)和平均动脉压(MAP)均显著升高(P<0.05),经过8周的运动训练后,SHR-L组和SHR-M组的BW、HR和MAP都较SHR安静组明显降低(P<0.05),且与SHR-L组相比,SHRM组MAP降低程度更为显著(P<0.05);2.与WKY组相比,SHR安静组MaxiK通道NPo值显著升高(P<0.05);与SHR安静组相比,经过8周运动训练后,SHR-L和SHR-M组MaxiK通道NPo值明显降低(P<0.05),且SHR-M组比SHR-L组的降低作用更为显著(P<0.05);3.与WKY组相比,SHR安静组β1亚基和α亚基蛋白表达水平均升高,但β1亚基升高程度较α亚基更明显,即β1/α比值显著升高(P<0.05),与SHR安静组相比,8周运动训练可显著降低β1/α比值(P<0.05),而且SHR-M组比SHR-L组的改善作用更为显著(P<0.05)。结论:有氧运动可以纠正高血压相关的肠系膜血管平滑肌MaxiK通道病理性重塑,并由此改善由高血压引起的该通道的病理改变,延缓并改善高血压症状,在低强度有氧运动到中强度有氧运动范围内,运动对高血压症状的改善作用具有运动强度的依赖性。
Abstract：Objective:The purpose of this study is to determine the effects of exercise intensity on hypertension-associated changes in large-conductance Ca2+-activated K+(MaxiK) channels in mesenteric arteries from spontaneously hypertensive rats(SHR).Methods:Male SHR(n=54) were randomly assigned to three groups:a low-intensity aerobic exercise group(SHR-L),a moderate-intensity aerobic exercise group(SHR-M),and a sedentary group(SHR).Age-matched male WKY(n=18)were used as normotensive controls.Aerobic exercise groups completed an 8-week exercise training.After 8 weeks of aerobic exercise,the segment of mesenteric arteries was carefully dissected free,and separated into smooth muscle cells by one step digestion.Results:SHR mesenteric arteries MaxiK channel subunit protein expression,β1/α ratio,whole cell current density and single-channel open probability was also increased compared with WKY(P<0.05).Aerobic exercise reduced systemic blood pressure and normalized hypertension-associated mesenteric arteries(P<0.05).MaxiK alterations to normotensive control levels in the SHR(P<0.05).These effects were more pronounced in the moderate-intensity group than in the low-intensity group.Conclusions:Aerobic exercise training can effectively correct the pathological adaptation of mesenteric arteries MaxiK channels in spontaneously hypertensive rats by downregulation of β1/α to restore the vascular function in mesenteric arteries,which are intensity/volume dependent.
[1]SCHMIEDER R E.End organ damage in hypertension[J].Dtsch Arztebl Int,2010,107(49):866-873.
[2]JOSEPH B K,THAKALI K M,MOORE C L,et al.Ion channel remodeling in vascular smooth muscle during hypertension:Implications for novel therapeutic approaches[J].Pharmacol Res,2013,70(1):126-138.
[3]HEISTAD D D,MAYHAN W G,COYLE P,et al.Impaired dilatation of cerebral arterioles in chronic hypertension[J].Blood Vessels,1990,27(2-5):258-262.
[4]HARDER D R,BRANN L,HALPERN W.Altered membrane electrical properties of smooth muscle cells from small cerebral arteries of hypertensive rats[J].Blood Vessels,1983,20(3):154-160.
[5]BRAYDEN J E,NELSON M T.Regulation of arterial tone by activation of calcium-dependent potassium channels[J].Science,1992,256(5056):532-535.
[6]AGARWAL D,WELSCH M A,KELLER J N,et al.Chronic exercise modulates RAS components and improves balance between pro-and anti-inflammatory cytokines in the brain of SHR[J].Basic Res Cardiol,2011,106(6):1069-1085.
[7]ROQUE F R,BRIONES A M,GARCíA-REDONDO A B,et al.Aerobic exercise reduces oxidative stress and improves vascular changes of small mesenteric and coronary arteries in hypertension[J].Br J Pharmacol,2013,168(3):686-703.
[8]SHI L,LIU B,XUE Z,et al.Aerobic exercise increases BKCachannel contribution to regulation of mesenteric arterial tone by up regulatingβ1-Subunit[J].Exp Physiol,2013,98(1):326-336.
[9]FOULDS H J,BREDIN S S,CHARLESWORTH S A,et al.Exercise volume and intensity:a dose–response relationship with health benefits[J].Eur J Appl Physiol,2014,114(8):1563-1571.
[10]WARBURTON D E,NICOL C W,BREDIN S S.Health benefits of physical activity:the evidence[J].Can Med Assoc J,2006,174(6):801-809.
[11]WEN C P,WAI J P,TSAI M K,et al.Minimum amount of physical activity for reduced mortality and extended life expectancy:a prospective cohort study[J].Lancet,2011,378(9798):1244-1253.
[12]KESANIEMI Y K,DANFORTH E J R,JENSEN M D,et al.Dose-response issues concerning physical activity and health:an evidencebased symposium[J].Med Sci Sports Exerc,2001,33(6):S351-S358.
[13]KOHL H W.Physical activity and cardiovascular disease:evidence for a dose response[J].Med Sci Sports Exerc,2001,33(6):S472-S483.
[14]HILL M A,YANG Y,ELLA S R,et al.Large conductance,Ca2+activated K+channels(BKCa)and arteriolar myogenic signaling[J].FEBS Lett,2010,584(10):2033-2042.
[15]KIM N,CHUNG J,KIM E,et al.Changes in the Ca2+activated K+channels of the coronary artery during lef tventricular hypertrophy[J].Circ Res,2003,93(6):541-547.
[16]ASANO M,MASUZAWA-ITO K,MATSUDA T.Charybdotoxin-sensitive K+channels regulate the myogenic tone in the resting state of arteries from spontaneously hypertensive rats[J].Br J Pharmacol,1993,108(1):214-222.
[17]LIU Y,HUDETZ A G,KNAUS H G,et al.Increased expression of Ca2+sensitive K+channels in aorta of hypertensive rats[J].Hypertension,1997,30(6):1403-1409.
[18]LIU Y,HUDETZ A G,KNAUS H G,et al.Increased expression of Ca2+sensitive K+channels in the cerebral microcirculation of genetically hypertensive rats:evidence for their protection against cerebral vasospasm[J].Circ Res,1998,82(6):729-737.
[19]MARTENS J R,GELBAND C H.Alterations in rat interlobar artery membrane potential and K+channels in genetic and nongenetic hypertension[J].Circ Res,1996,79(2):295-301.
[20]RUSCH N J,RUNNELLS A M.Remission of high blood pressure reverses arterial potassium channel alterations[J].Hypertension,1994,23(2-6):941-945.
[21]LIU Y,PLEYTE K,KNAUS H G,et al.Increased expression of Ca2+sensitive K+channels in aorta of hypertensive rats[J].Hypertension,1997,30(6):1403-1409.
[22]XU H,BIAN X,WATTS S W,et al.Activation of vascular BK channel by tempol in DOCA salt hypertensive rats[J].Hypertension,2005,46(5):1154-1162.
[23]LI N,SHI Y,SHI L,et al.The effect of aerobic exercise training on the biophysical properties of BKCachannels in rat cerebral artery smooth muscle cells[J].Eur J Appl Physiol,2013,113(10):2553-2563.
[24]ZHAO H C,WANG F.Exercise training changes the gating properties of large conductance Ca2+activated K+channels in rat thoracic aorta smooth muscle cells[J].J Biomech,2010,43(2):263-267.
[25]JOSEPH B K,THAKALI K M,MOORE C L,et al.Ion channel remodeling in vascular smooth muscle during hypertension:Implications for novel therapeutic approaches[J].Pharmacol Res,2013,70(1):126-138.
[26]ZHANG Y,GAO Y J,ZUO J,et al.Alteration of arterial smooth muscle potassium channel composition and BKCacurrent modulation in hypertension[J].Eur J Pharmacol,2005,514(2-3):111-119.
[27]BRENNER R,PERéZ G J,BONEV A D,et al.Vasoregulation by the beta1 subunit of the calcium-activated potassium channel[J].Nature,2000,407(6806):870-876.
[28]PLüGER S,FAULHABER J,FüRSTENAU M,et al.Mice with disrupted BK channel beta1 subunit gene feature abnormal Ca2+spark/STOC coupling and elevated blood pressure[J].Circ Res,2000,87(11):E53-E60.
[29]AMBERG G C,SANTANA L F.Downregulation of the BK channel beta1 subunit in genetic hypertension[J].Circ Res,2003,93(10):965-971.
[30]ZHAO G,ZHAO Y,PAN B,et al.Hypersensitivity of BKCato Ca2+sparks underlies hyporeactivity of arterial smooth muscle in shock[J].Circ Res,2007,101(5):493-502.
[31]COX R H,RUSCH N J.New expression profiles of voltage-gated ion channels in arteries exposed to high blood pressure[J].Microcirculation,2002,9(4):243-257.
基本信息:
DOI：10.13297/j.cnki.issn1005-0000.2016.06.004
中图分类号:G804.2
引用信息:
[1]徐召霞,赵腾腾,柏平,等.不同强度有氧运动对SHR动脉平滑肌MaxiK通道功能重构的影响[J].天津体育学院学报,2016,31(06):479-484.DOI:10.13297/j.cnki.issn1005-0000.2016.06.004.
基金信息:
国家自然科学基金项目(项目编号:31371201);; 体育总局科研课题资助项目(项目编号:2015B035)