有氧运动通过抑制血管紧张素Ⅱ途径改善原发性高血压患者骨骼肌功能性抗交感研究
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摘要
目的:探讨有氧运动是否通过抑制血管紧张素Ⅱ(angiotensin Ⅱ,Ang Ⅱ)途径改善原发性高血压患者骨骼肌功能性抗交感。方法:36名未经治疗的男性I级原发性高血压患者(收缩压SBP/舒张压DBP:140～159/90～99 mmHg)随机分为运动组(E,n=20)和服药组(D,n=16),E组进行有氧运动,D组服用降压药美托洛尔(β_1-肾上腺素受体阻断剂),干预时间为12周。分别于实验前后:1)测定血压水平的变化;2)利用冷加压实验(CPT)激活交感神经,测定安静时以及握力运动时的前臂血液动力学,交感缩血管反应采用CPT诱导前臂血管电导(FVC)的变化率(%FVC)表示,功能性抗交感(即骨骼肌收缩抑制交感缩血管反应的能力)用肌肉收缩时CPT诱导FVC的变化率与安静时的差值(△%FVC)表示;3)静脉滴注Ang Ⅱ以诱导氧化应激和缩血管反应,测定前臂血管阻力(FVR)和血清8-异前列腺素F_2α(8-iso-PGF_2α)含量。结果:1)血压水平:实验后,E组和D组安静以及握力运动时的血压水平(SBP、DBP和MAP)均显著性下降(P<0.05),但下降幅度组间比较并无显著性差异(P>0.05)。2)交感缩血管反应(%FVC)和功能性抗交感(△%FVC):实验后,E组安静时%FVC升高(P<0.05)、握力运动时%FVC降低(P<0.05),△%FVC增加(P<0.05),D组均无显著性变化(P>0.05)。3)Ang Ⅱ滴注实验:实验前E组和D组FVR和血清8-iso-PGF_2α含量在滴注Ang Ⅱ时均显著性升高(P<0.05),实验后E组无显著性变化(P>0.05),D组则仍高于滴注前水平(P<0.05)。结论:长期有氧运动通过抑制Ang Ⅱ途径改善I级原发性高血压患者骨骼肌功能性抗交感,然而这一效应与血压下降并无关联。
Objective: To investigate whether aerobic exercise improves skeletal muscle functional sympatholysis via inhibition of angiotensin Ⅱ(Ang Ⅱ) pathway in essential hypertension patients. Methods: 36 untreated male stage 1 essential hypertension patients(systolic blood pressure(SBP)/diastolic blood pressure(DBP): 140～159/90～99 mmHg) randomly divided into exercise(E) group ( n = 20) and drug administration( D) group( n = 16) performed aerobic exercise or antihypertensive agent Metoprolol( β1-adrenergic receptor blocker) for 12 weeks. Before and after experiment:1) change of blood pressure level was determined; 2) forearm hemodynamic responses to reflex increases in sympathetic nerve activity evoked by cold pressor test( CPT) at rest and during handgrip exercise were determined. Sympathetic vasoconstriction was represented as forearm vascular conductance( FVC) change rate( △% FVC) and functional sympatholysis( the capacity of skeletal muscle contraction to suppress sympathetic vasoconstrictor response) as the difference of CPT induced FVC change rate between during muscular contraction and at rest( △% FVC); 3) intravenous infusion of Ang Ⅱ was conducted to induce oxidative stress and vasoconstriction and forearm vascular resistance( FVR) as well as serum 8-iso-prostaglandin( 8-iso-PGF2α) content were measured. Results:1) Blood pressure level: after test,blood pressure( SBP,DBP and MAP) at rest and and during handgrip exercise reduced in both E and D groups( P < 0. 05),but there was no significant difference of reduction extent between groups( P > 0. 05). 2) sympathetic vasoconstriction response( %FVC) and functional sympatholysis( △% FVC) : after experiment,% FVC at rest and △% FVC increased while % FVC during handgrip exercise decreased in E group( P < 0. 05),but the effects above were not observed in D group( P > 0. 05). 3) Ang Ⅱ infusion test: after infusion,FVR and serum 8-iso-PGF2α increased of both E and D groups before experiment( P < 0. 05); after experiment,there was no sighnificant change in E group( P > 0. 05) while still higher than pre-infusion in D group( P < 0. 05). Conclusion: Long-term aerobic exercise improved skeletal muscle functional sympatholysis via inhibition of Ang Ⅱ pathway but not reduction of blood pressure in stage1 essential hypertension patients.
Objective: To investigate whether aerobic exercise improves skeletal muscle functional sympatholysis via inhibition of angiotensin Ⅱ(Ang Ⅱ) pathway in essential hypertension patients. Methods: 36 untreated male stage 1 essential hypertension patients(systolic blood pressure(SBP)/diastolic blood pressure(DBP): 140～159/90～99 mmHg) randomly divided into exercise(E) group ( n = 20) and drug administration( D) group( n = 16) performed aerobic exercise or antihypertensive agent Metoprolol( β1-adrenergic receptor blocker) for 12 weeks. Before and after experiment:1) change of blood pressure level was determined; 2) forearm hemodynamic responses to reflex increases in sympathetic nerve activity evoked by cold pressor test( CPT) at rest and during handgrip exercise were determined. Sympathetic vasoconstriction was represented as forearm vascular conductance( FVC) change rate( △% FVC) and functional sympatholysis( the capacity of skeletal muscle contraction to suppress sympathetic vasoconstrictor response) as the difference of CPT induced FVC change rate between during muscular contraction and at rest( △% FVC); 3) intravenous infusion of Ang Ⅱ was conducted to induce oxidative stress and vasoconstriction and forearm vascular resistance( FVR) as well as serum 8-iso-prostaglandin( 8-iso-PGF2α) content were measured. Results:1) Blood pressure level: after test,blood pressure( SBP,DBP and MAP) at rest and and during handgrip exercise reduced in both E and D groups( P < 0. 05),but there was no significant difference of reduction extent between groups( P > 0. 05). 2) sympathetic vasoconstriction response( %FVC) and functional sympatholysis( △% FVC) : after experiment,% FVC at rest and △% FVC increased while % FVC during handgrip exercise decreased in E group( P < 0. 05),but the effects above were not observed in D group( P > 0. 05). 3) Ang Ⅱ infusion test: after infusion,FVR and serum 8-iso-PGF2α increased of both E and D groups before experiment( P < 0. 05); after experiment,there was no sighnificant change in E group( P > 0. 05) while still higher than pre-infusion in D group( P < 0. 05). Conclusion: Long-term aerobic exercise improved skeletal muscle functional sympatholysis via inhibition of Ang Ⅱ pathway but not reduction of blood pressure in stage1 essential hypertension patients.
引文
[1]Fadel PJ.Reflex control of the circulation during exercise[J].Scand J Med Sci Sports,2015(25 Suppl 4):74-82.
[2]Dodd LR,Johnson PC.Functional sympatholysis in the microcirculation of the cat sartorius muscle[J].Proc West Pharmacol Soc,1988(31):121-123.
[3]Vongpatanasin W,Wang Z,Arbique D,et al.Functional sympatholysis is impaired in hypertensive humans[J].J Physiol,2011,589(Pt 5):1209-1220.
[4]Te RL,van Esch JH,Roks AJ,et al.Hypertension:renin-angiotensin-aldosterone system alterations[J].Circ Res,2015,116(6):960-975.
[5]Zhao W,Swanson SA,Ye J,et al.Reactive oxygen species impair sympathetic vasoregulation in skeletal muscle in angiotensin II-dependent hypertension[J].Hypertension,2006,48(4):637-643.
[6]Ghadieh AS,Saab B.Evidence for exercise training in the management of hypertension in adults[J].Can Fam Physician,2015,61(3):233-239.
[7]程蕾.有氧运动和抗心衰药物联合作用对慢性心衰患者红细胞分布宽度、心功能及运动能力的影响[J].中国体育科技,2013,49(1):52-56 .
[8]程蕾,李晓霞.10周有氧训练对心力衰竭大鼠心脏重塑和运动耐力的影响[J].山东体育学院学报,2015,35(1):80-84.
[9]Silva SD,Jara ZP,Peres R,et al.Temporal changes in cardiac oxidative stress,inflammation and remodeling induced by exercise in hypertension:Role for local angiotensin II reduction[J].PLoS One,2017,12(12):e0189535.
[10]孙一,朱荣,李学恒,等.不同强度运动对骨骼肌功能性抗交感活性的影响[J].北京体育大学学报,2017,40(10):50-55.
[11]孙一,朱荣,李学恒,等.长期有氧运动改善中年原发性高血压患者功能性抗交感活性[J].西安体育学院学报,2018,35(1):1-13.
[12]Horiuchi M,Endo J,Thijssen DH.Impact of ischemic preconditioning on functional sympatholysis during handgrip exercise in humans[J].Physiol Rep,2015,3(2):1-9.
[13]Price A,Raheja P,Wang Z,et al.Differential effects of nebivolol versus metoprolol on functional sympatholysis in hypertensive humans[J].Hypertension,2013,61(6):1263-1269.
[14]Wray DW,Donato AJ,Nishiyama SK,et al.Acute sympathetic vasoconstriction at rest and during dynamic exercise in cyclists and sedentary humans[J].J Appl Physiol (1985),2007,102(2):704-712.
[15]Egan B,Panis R,Hinderliter A,et al.Mechanism of increased alpha adrenergic vasoconstriction in human essential hypertension[J].J Clin Invest,1987,80(3):812-817.
[16]Victor RG,Leimbach WN,Seals DR,et al.Effects of the cold pressor test on muscle sympathetic nerve activity in humans[J].Hypertension,1987,9(5):429-436.
[17]Horiuchi M,Fadel PJ,Ogoh S.Differential effect of sympathetic activation on tissue oxygenation in gastrocnemius and soleus muscles during exercise in humans[J].Exp Physiol,2014,99(2):348-358.
[18]Mortensen SP,M?rkeberg J,Thaning P,et al.Two weeks of muscle immobilization impairs functional sympatholysis but increases exercise hyperemia and the vasodilatory responsiveness to infused ATP[J].Am J Physiol Heart Circ Physiol,2012,302(10):H2074-2082.
[19]Donato AJ,Lesniewski LA,Delp MD.Ageing and exercise training alter adrenergic vasomotor responses of rat skeletal muscle arterioles[J].J Physiol,2007,579(Pt 1):115-125.
[20]Mortensen SP,Nyberg M,Winding K,et al.Lifelong physical activity preserves functional sympatholysis and purinergic signalling in the ageing human leg[J].J Physiol,2012,590(23):6227-6236.
[21]Wimer GS,Baldi JC.Limb-specific training affects exercise hyperemia but not sympathetic vasoconstriction[J].Eur J Appl Physiol,2012,112(11):3819-3828.
[22]Jendzjowsky NG,DeLorey DS.Short-term exercise training augments 2-adrenoreceptor-mediated sympathetic vasoconstriction in resting and contracting skeletal muscle[J].J Physiol,2013,591(20):5221-5233.
[23]Jendzjowsky NG,Delorey DS.Short-term exercise training enhances functional sympatholysis through a nitric oxide-dependent mechanism[J].J Physiol,2013,591(6):1535-1549.
[24]Jendzjowsky NG,DeLorey DS.Short-term exercise training augments sympathetic vasoconstrictor responsiveness and endothelium-dependent vasodilation in resting skeletal muscle[J].Am J Physiol Regul Integr Comp Physiol,2012,303(3):R332-339.
[25]Lash JM.Exercise training enhances adrenergic constriction and dilation in the rat spinotrapezius muscle[J].J Appl Physiol (1985),1998,85(1):168-174.
[26]McAllister RM,Laughlin MH.Short-term exercise training alters responses of porcine femoral and brachial arteries[J].J Appl Physiol (1985),1997,82(5):1438-1444.
[27]Delp MD,McAllister RM,Laughlin MH.Exercise training alters endothelium-dependent vasoreactivity of rat abdominal aorta[J].J Appl Physiol (1985),1993,75(3):1354-1363.
[28]Mortensen SP,Nyberg M,Gliemann L,et al.Exercise training modulates functional sympatholysis and α-adrenergic vasoconstrictor responsiveness in hypertensive and normotensive individuals[J].J Physiol,2014,592(14):3063-3073.
[29]Edwards JG,Tipton CM,Matthes RD.Influence of exercise training on reactivity and contractility of arterial strips from hypertensive rats[J].J Appl Physiol (1985),1985,58(5):1683-1688.
[30]Smith ML,Graitzer HM,Hudson DL,et al.Baroreflex function in endurance- and static exercise-trained men[J].J Appl Physiol (1985),1988,64(2):585-591.
[31]Thomas GD.Functional sympatholysis in hypertension[J].Auton Neurosci,2015,188:64-68.
[32]Azadpour N,Tartibian B,Ko?ar ?N.Effects of aerobic exercise training on ACE and ADRB2 gene expression,plasma angiotensin II level,and flow-mediated dilation:a study on obese postmenopausal women with prehypertension[J].Menopause,2017,24(3):269-277.
[33]Lee S,Hashimoto J,Suzuki T,et al.The effects of exercise load during development on oxidative stress levels and antioxidant potential in adulthood[J].Free Radic Res,2017,51(2):179-186.
[34]Medeiros-Lima DJ,Mendes-Ribeiro AC,Brunini TM,et al.Erythrocyte nitric oxide availability and oxidative stress following exercise[J].Clin Hemorheol Microcirc,2017,65(3):219-228.
[35]Yasue S,Ebihara K,Nakao K.Adipose tissue renin-angiotensin system in obese[J].Nihon Rinsho,2012,70(9):1550-1555.
[36]Thomas GD,Zhang W,Victor RG.Impaired modulation of sympathetic vasoconstriction in contracting skeletal muscle of rats with chronic myocardial infarctions:role of oxidative stress[J].Circ Res,2001,88(8):816-823.
[37]Fongemie J,Felix-Getzik E.A review of nebivolol pharmacology and clinical evidence[J].Drugs,2015,75(12):1349-1371.
[38]Bayar E,Ilhan G,Furat C,et al.The effect of different β-blockers on vascular graft nitric oxide levels:comparison of nebivolol versus metoprolol[J].Eur J Vasc Endovasc Surg,2014,47(2):204-208.
[39]Velasco A,Solow E,Price A,et al.Differential effects of nebivolol vs.metoprolol on microvascular function in hypertensive humans[J].Am J Physiol Heart Circ Physiol,2016,311(1):H118-124.
[2]Dodd LR,Johnson PC.Functional sympatholysis in the microcirculation of the cat sartorius muscle[J].Proc West Pharmacol Soc,1988(31):121-123.
[3]Vongpatanasin W,Wang Z,Arbique D,et al.Functional sympatholysis is impaired in hypertensive humans[J].J Physiol,2011,589(Pt 5):1209-1220.
[4]Te RL,van Esch JH,Roks AJ,et al.Hypertension:renin-angiotensin-aldosterone system alterations[J].Circ Res,2015,116(6):960-975.
[5]Zhao W,Swanson SA,Ye J,et al.Reactive oxygen species impair sympathetic vasoregulation in skeletal muscle in angiotensin II-dependent hypertension[J].Hypertension,2006,48(4):637-643.
[6]Ghadieh AS,Saab B.Evidence for exercise training in the management of hypertension in adults[J].Can Fam Physician,2015,61(3):233-239.
[7]程蕾.有氧运动和抗心衰药物联合作用对慢性心衰患者红细胞分布宽度、心功能及运动能力的影响[J].中国体育科技,2013,49(1):52-56 .
[8]程蕾,李晓霞.10周有氧训练对心力衰竭大鼠心脏重塑和运动耐力的影响[J].山东体育学院学报,2015,35(1):80-84.
[9]Silva SD,Jara ZP,Peres R,et al.Temporal changes in cardiac oxidative stress,inflammation and remodeling induced by exercise in hypertension:Role for local angiotensin II reduction[J].PLoS One,2017,12(12):e0189535.
[10]孙一,朱荣,李学恒,等.不同强度运动对骨骼肌功能性抗交感活性的影响[J].北京体育大学学报,2017,40(10):50-55.
[11]孙一,朱荣,李学恒,等.长期有氧运动改善中年原发性高血压患者功能性抗交感活性[J].西安体育学院学报,2018,35(1):1-13.
[12]Horiuchi M,Endo J,Thijssen DH.Impact of ischemic preconditioning on functional sympatholysis during handgrip exercise in humans[J].Physiol Rep,2015,3(2):1-9.
[13]Price A,Raheja P,Wang Z,et al.Differential effects of nebivolol versus metoprolol on functional sympatholysis in hypertensive humans[J].Hypertension,2013,61(6):1263-1269.
[14]Wray DW,Donato AJ,Nishiyama SK,et al.Acute sympathetic vasoconstriction at rest and during dynamic exercise in cyclists and sedentary humans[J].J Appl Physiol (1985),2007,102(2):704-712.
[15]Egan B,Panis R,Hinderliter A,et al.Mechanism of increased alpha adrenergic vasoconstriction in human essential hypertension[J].J Clin Invest,1987,80(3):812-817.
[16]Victor RG,Leimbach WN,Seals DR,et al.Effects of the cold pressor test on muscle sympathetic nerve activity in humans[J].Hypertension,1987,9(5):429-436.
[17]Horiuchi M,Fadel PJ,Ogoh S.Differential effect of sympathetic activation on tissue oxygenation in gastrocnemius and soleus muscles during exercise in humans[J].Exp Physiol,2014,99(2):348-358.
[18]Mortensen SP,M?rkeberg J,Thaning P,et al.Two weeks of muscle immobilization impairs functional sympatholysis but increases exercise hyperemia and the vasodilatory responsiveness to infused ATP[J].Am J Physiol Heart Circ Physiol,2012,302(10):H2074-2082.
[19]Donato AJ,Lesniewski LA,Delp MD.Ageing and exercise training alter adrenergic vasomotor responses of rat skeletal muscle arterioles[J].J Physiol,2007,579(Pt 1):115-125.
[20]Mortensen SP,Nyberg M,Winding K,et al.Lifelong physical activity preserves functional sympatholysis and purinergic signalling in the ageing human leg[J].J Physiol,2012,590(23):6227-6236.
[21]Wimer GS,Baldi JC.Limb-specific training affects exercise hyperemia but not sympathetic vasoconstriction[J].Eur J Appl Physiol,2012,112(11):3819-3828.
[22]Jendzjowsky NG,DeLorey DS.Short-term exercise training augments 2-adrenoreceptor-mediated sympathetic vasoconstriction in resting and contracting skeletal muscle[J].J Physiol,2013,591(20):5221-5233.
[23]Jendzjowsky NG,Delorey DS.Short-term exercise training enhances functional sympatholysis through a nitric oxide-dependent mechanism[J].J Physiol,2013,591(6):1535-1549.
[24]Jendzjowsky NG,DeLorey DS.Short-term exercise training augments sympathetic vasoconstrictor responsiveness and endothelium-dependent vasodilation in resting skeletal muscle[J].Am J Physiol Regul Integr Comp Physiol,2012,303(3):R332-339.
[25]Lash JM.Exercise training enhances adrenergic constriction and dilation in the rat spinotrapezius muscle[J].J Appl Physiol (1985),1998,85(1):168-174.
[26]McAllister RM,Laughlin MH.Short-term exercise training alters responses of porcine femoral and brachial arteries[J].J Appl Physiol (1985),1997,82(5):1438-1444.
[27]Delp MD,McAllister RM,Laughlin MH.Exercise training alters endothelium-dependent vasoreactivity of rat abdominal aorta[J].J Appl Physiol (1985),1993,75(3):1354-1363.
[28]Mortensen SP,Nyberg M,Gliemann L,et al.Exercise training modulates functional sympatholysis and α-adrenergic vasoconstrictor responsiveness in hypertensive and normotensive individuals[J].J Physiol,2014,592(14):3063-3073.
[29]Edwards JG,Tipton CM,Matthes RD.Influence of exercise training on reactivity and contractility of arterial strips from hypertensive rats[J].J Appl Physiol (1985),1985,58(5):1683-1688.
[30]Smith ML,Graitzer HM,Hudson DL,et al.Baroreflex function in endurance- and static exercise-trained men[J].J Appl Physiol (1985),1988,64(2):585-591.
[31]Thomas GD.Functional sympatholysis in hypertension[J].Auton Neurosci,2015,188:64-68.
[32]Azadpour N,Tartibian B,Ko?ar ?N.Effects of aerobic exercise training on ACE and ADRB2 gene expression,plasma angiotensin II level,and flow-mediated dilation:a study on obese postmenopausal women with prehypertension[J].Menopause,2017,24(3):269-277.
[33]Lee S,Hashimoto J,Suzuki T,et al.The effects of exercise load during development on oxidative stress levels and antioxidant potential in adulthood[J].Free Radic Res,2017,51(2):179-186.
[34]Medeiros-Lima DJ,Mendes-Ribeiro AC,Brunini TM,et al.Erythrocyte nitric oxide availability and oxidative stress following exercise[J].Clin Hemorheol Microcirc,2017,65(3):219-228.
[35]Yasue S,Ebihara K,Nakao K.Adipose tissue renin-angiotensin system in obese[J].Nihon Rinsho,2012,70(9):1550-1555.
[36]Thomas GD,Zhang W,Victor RG.Impaired modulation of sympathetic vasoconstriction in contracting skeletal muscle of rats with chronic myocardial infarctions:role of oxidative stress[J].Circ Res,2001,88(8):816-823.
[37]Fongemie J,Felix-Getzik E.A review of nebivolol pharmacology and clinical evidence[J].Drugs,2015,75(12):1349-1371.
[38]Bayar E,Ilhan G,Furat C,et al.The effect of different β-blockers on vascular graft nitric oxide levels:comparison of nebivolol versus metoprolol[J].Eur J Vasc Endovasc Surg,2014,47(2):204-208.
[39]Velasco A,Solow E,Price A,et al.Differential effects of nebivolol vs.metoprolol on microvascular function in hypertensive humans[J].Am J Physiol Heart Circ Physiol,2016,311(1):H118-124.