Long-term aerobic exercise enhances the production of endogenous hydrogen sulfide in the kidney of spontaneously hypertensive rats

doi:10.3969/j.issn.2095-4344.2016.27.020

Abstract

Abstract:

BACKGROUND: It is well known that long-term aerobic exercise alleviates renal dysfunction in spontaneously hypertensive rats. However, the underlying molecular mechanism remains unclear.
OBJECTIVE: To investigate the effect of long-term aerobic exercise on endogenous formation of hydrogen sulfide in the kidney of spontaneously hypertensive rats.
METHODS: Rat models of long-term aerobic exercise were established and randomly assigned to four groups: Wistar-Kyoto (WKY) rat static group, WKY rat exercise group, spontaneously hypertensive rat static group and spontaneously hypertensive rat exercise group. Moderate-intensity exercise on treadmill was given for 12 weeks. At 24 hours after model establishment, weight was weighted. Blood pressure was detected in the caudal artery. Blood and urine were collected for measuring biochemical indicators related to kidney functions. The degree of glomerular sclerosis was observed. Hydrogen sulfide production activity was detected in the kidney. RT-PCR was used to detect mRNA expression levels of hydrogen sulfide production-related enzymes. Simultaneously, oxidative stress of the kidney was observed.
RESULTS AND CONCLUSION: (1) Long-term aerobic exercise obviously reduced body mass, systolic blood pressure and diastolic blood pressure, increased glomerular filtration rate and renal blood flow, decreased serum creatinine and urea nitrogen levels, urinary albumin levels, significantly reduced glomerular sclerosis score, increased hydrogen sulfide content in plasma and the rate of hydrogen sulfide formation in renal tissue, up-regulated cystathionine γ-lyase expression, obviously diminished malondialdehyde content in serum and kidney, and remarkably increased the reduced glutathione and oxidized glutathione ratio in spontaneously hypertensive rats. (2) Results indicated that long-term aerobic exercise could increase the generation of endogenous hydrogen sulfide in kidney, lessen oxidative stress in the kidney, and ameliorate renal dysfunction in spontaneously hypertensive rats.

中国组织工程研究杂志出版内容重点：肾移植；肝移植；移植；心脏移植；组织移植；皮肤移植；皮瓣移植；血管移植；器官移植；组织工程

Key words: Models, Animal, Hydrogen Sulfide, Glutathione, Tissue Engineering

CLC Number:

R318

Wang Bing, Hou Jun, Gu Qi . Long-term aerobic exercise enhances the production of endogenous hydrogen sulfide in the kidney of spontaneously hypertensive rats[J]. Chinese Journal of Tissue Engineering Research, 2016, 20(27): 4090-4097.

Figures/Tables 2

2.1 实验动物数量分析实验分为4组，即WKY大鼠静止组、WKY大鼠运动组、自发性高血压大鼠静止组及自发性高血压大鼠运动组，每组12只。全部进入结果分析，无脱失。 2.2 长期有氧运动对自发性高血压大鼠血压和体质量的影响如表1所示，与WKY大鼠静止组相比，自发性高血压大鼠的收缩压、舒张压、心率明显增高，体质量变化不大；而经过长期的有氧运动之后，自发性高血压大鼠的体质量、收缩压、舒张压明显降低，心率变化不明显。 WKY大鼠经过长期有氧运动后，体质量明显下降，但是收缩压、舒张压、心率变化不明显。 2.3 长期有氧运动改善自发性高血压大鼠的肾脏功能与WKY大鼠静止组相比，自发性高血压大鼠肾小球滤过率(图1A)和肾血流量(图1B)降低，血肌酐(图1C)和尿素氮(图1D)水平增加，尿白蛋白(图1E)水平增加，肾小球硬化评分(图1F)明显增加；而经过长期的有氧运动之后，自发性高血压大鼠肾小球滤过率和肾血流量增加，血肌酐和尿素氮水平降低，尿白蛋白水平降低，肾小球硬化评分明显降低。 WKY大鼠经过长期有氧运动后，肾脏的各项指标没有明显变化。 2.4 长期有氧运动增加自发性高血压大鼠肾脏内源性H2S的生成与WKY大鼠静止组相比，自发性高血压大鼠血浆中H2S含量明显减少(图2A)；肾脏组织中H2S生成速率明显降低(图2B)；肾脏中H2S合成相关酶(图2C)：胱硫醚β合酶和3-巯基丙酮酸硫基转移酶的表达没有明显变化，而胱硫醚γ分解酶表达明显降低。而经过长期的有氧运动之后，自发性高血压大鼠血浆中H2S含量和肾脏组织中H2S生成速率明显增加；胱硫醚γ分解酶表达明显上调。 WKY大鼠经过长期有氧运动后，H2S生成的各项指标没有明显变化。 2.5 长期有氧运动减轻肾脏内氧化应激的状态与WKY大鼠静止组相比，自发性高血压大鼠血清中(图3A)和肾脏(图3B)中丙二醛(脂质过氧化产物，氧化应激的标志之一)含量明显增加；还原型谷胱甘肽和氧化型谷胱甘肽比值明显降低(图3C)。而经过长期的有氧运动之后，自发性高血压大鼠血清中和肾脏中丙二醛含量明显降低；还原型谷胱甘肽和氧化型谷胱甘肽比值明显增加，提示长期有氧运动可以减轻自发性高血压大鼠肾脏内氧化应激的状态。 WKY大鼠经过长期有氧运动后，氧化应激的各项指标没有明显变化。"

References

[1] Navaneethan SD, Schold JD, Arrigain S, et al. Body mass index and causes of death in chronic kidney disease. Kidney Int.2016;89:675-682.
[2] Hall ME, do Carmo JM, da Silva AA, et al. Obesity, hypertension, and chronic kidney disease. Int J Nephrol Renovasc Dis.2014;7:75-88.
[3] Townsend RR, Taler SJ. Management of hypertension in chronic kidney disease. Nat Rev Nephrol. 2015;11: 555-563.
[4] Sabino JP, Traslaviña GA, Branco LG. Role of central hydrogen sulfide on ventilatory and cardiovascular responses to hypoxia in spontaneous hypertensive rats. Respir Physiol Neurobiol. 2016. pii: S1569-9048(16)30093-3.
[5] Bidani AK, Polichnowski AJ, Loutzenhiser R, et al. Renal microvascular dysfunction, hypertension and CKD progression. Curr Opin Nephrol Hypertens. 2013; 22:1-9.
[6] Hashimoto J, Ito S. Aortic Blood Flow Reversal Determines Renal Function: Potential Explanation for Renal Dysfunction Caused by Aortic Stiffening in Hypertension. Hypertension. 2015;66:61-67.
[7] Lamina S, Okoye CG, Hanif SM. Randomised controlled trial: effects of aerobic exercise training programme on indices of adiposity and metabolic markers in hypertension. J Pak Med Assoc.2013;63:680-687.
[8] Lee LL, Watson MC, Mulvaney CA, et al. The effect of walking intervention on blood pressure control: A systematic review. Int J Nurs Stud.2010;47:1545-1561.
[9] Ghadieh AS, Saab B. Evidence for exercise training in the management of hypertension in adults. Can Fam Physician. 2015;61:233-239.
[10] Sharman JE, La Gerche A, Coombes JS. Exercise and cardiovascular risk in patients with hypertension. Am J Hypertens. 2015;28:147-158.
[11] Buys R, Avila A, Cornelissen VA. Exercise training improves physical fitness in patients with pulmonary arterial hypertension: a systematic review and meta-analysis of controlled trials. BMC Pulm Med. 2015; 15:40.
[12] Ribeiro F, Costa R, Mesquita-Bastos J. Exercise training in the management of patients with resistant hypertension. World J Cardiol. 2015;7:47-51.
[13] Chang Y, Cheng SY, Lin M, et al.The effectiveness of intradialytic leg ergometry exercise for improving sedentary life style and fatigue among patients with chronic kidney disease: a randomized clinical trial. Int J Nurs Stud.2010;47:1383-1388.
[14] Henrique DM, Reboredo Mde M, Chaoubah A, et al. Aerobic exercise improves physical capacity in patients under chronic hemodialysis. Arq Bras Cardiol. 2010;94: 823-828.
[15] Barcellos FC, Santos IS, Mielke GI, et al. Effects of exercise on kidney function among non-diabetic patients with hypertension and renal disease: randomized controlled trial. BMC Nephrol. 2012;13:90.
[16] Maia RC, Sousa LE, Santos RA, et al. Time-course effects of aerobic exercise training on cardiovascular and renal parameters in 2K1C renovascular hypertensive rats. Braz J Med Biol Res. 2015;48:1010-1022.
[17] MacKinnon HJ, Feehally J, Smith AC. A review of the role of exercise and factors affecting its uptake for people with chronic kidney disease (CKD) not requiring renal replacement therapy. Prilozi. 2015;36:37-46.
[18] Aucella F, Valente GL, Catizone L. The role of physical activity in the CKD setting. Kidney Blood Press Res. 2014;39:97-106.
[19] Gu Q, Zhao L, Ma YP, et al. Contribution of mitochondrial function to exercise-induced attenuation of renal dysfunction in spontaneously hypertensive rats. Mol Cell Biochem. 2015;406:217-225.
[20] Be?towski J. Hydrogen sulfide in pharmacology and medicine--An update. Pharmacol Rep. 2015;67: 647-658.
[21] Snijder PM, Frenay AR, Koning AM, et al. Sodium thiosulfate attenuates angiotensin II-induced hypertension, proteinuria and renal damage. Nitric Oxide. 2014;42:87-98.
[22] Huang P, Chen S, Wang Y, et al. Down-regulated CBS/H2S pathway is involved in high-salt-induced hypertension in Dahl rats. Nitric Oxide. 2015;46: 192-203.
[23] Holwerda KM, Burke SD, Faas MM, et al. Hydrogen sulfide attenuates sFlt1-induced hypertension and renal damage by upregulating vascular endothelial growth factor. J Am Soc Nephrol. 2014;25:717-725.
[24] Ahmad FU, Sattar MA, Rathore HA, et al. Hydrogen sulphide and tempol treatments improve the blood pressure and renal excretory responses in spontaneously hypertensive rats. Ren Fail. 2014; 36:598-605.
[25] Xin HG, Zhang BB, Wu ZQ, et al. Consumption of hydrogen-rich water alleviates renal injury in spontaneous hypertensive rats. Mol Cell Biochem. 2014;392:117-124.
[26] Xia M, Chen L, Muh RW, et al. Production and actions of hydrogen sulfide, a novel gaseous bioactive substance, in the kidneys. J Pharmacol Exp Ther. 2009;329:1056-1062.
[27] Yang G, Wu L, Jiang B, et al. H2S as a physiologic vasorelaxant: hypertension in mice with deletion of cystathionine gamma-lyase. Science. 2008;322 (5901):587-590.
[28] Heyman SN, Brezis M, Greenfeld Z, et al. Protective role of furosemide and saline in radiocontrast-induced acute renal failure in the rat. Am J Kidney Dis .1989;14: 377-385.
[29] Tanaka T, Nangaku M. The role of hypoxia, increased oxygen consumption, and hypoxia-inducible factor-1 alpha in progression of chronic kidney disease. Curr Opin Nephrol Hypertens. 2010;19:43-50.
[30] Muzaffar S, Shukla N, Bond M, et al. Exogenous hydrogen sulfide inhibits superoxide formation, NOX-1 expression and Rac1 activity in human vascular smooth muscle cells. J Vasc Res .2008;45:521-528.
[31] Xie ZZ, Liu Y, Bian JS. Hydrogen Sulfide and Cellular Redox Homeostasis.Oxid Med Cell Longev. 2016: 6043038.
[32] Sen U, Munjal C, Qipshidze N, et al. Hydrogen sulfide regulates homocysteine-mediated glomerulosclerosis. Am J Nephrol. 2010;31:442-455.
[33] Lo Faro ML, Fox B, Whatmore JL, et al. Hydrogen sulfide and nitric oxide interactions in inflammation. Nitric Oxide. 2014;41:38-47.
[34] Manning RD Jr, Tian N, Meng S. Oxidative stress and antioxidant treatment in hypertension and the associated renal damage. Am J Nephrol. 2005;25: 311-317.
[35] Yoon JW, Pahl MV, Vaziri ND. Spontaneous leukocyte activation and oxygen-free radical generation in end-stage renal disease. Kidney Int. 2007;71:167-172.
[36] Pan X, Zhang Y, Tao S. Effects of Tai Chi exercise on blood pressure and plasma levels of nitric oxide, carbon monoxide and hydrogen sulfide in real-world patients with essential hypertension. Clin Exp Hypertens. 2015;37:8-14.
[37] Gu Q, Wang B, Zhang XF, et al. Contribution of hydrogen sulfide and nitric oxide to exercise-induced attenuation of aortic remodeling and improvement of endothelial function in spontaneously hypertensive rats. Mol Cell Biochem. 2013;375:199-206.
[38] 姚璐,张缨,张连峰.跑台运动在动物实验研究中的应用[J].中国比较医学杂志,2010,20(6):75-81.
[39] Gu Q, Wang B, Zhang XF, et al. Contribution of renin-angiotensin system to exercise-induced attenuation of aortic remodeling and improvement of endothelial function in spontaneously hypertensive rats. Cardiovasc Pathol. 2014;23:298-305.
[40] Gu Q, Wang B, Zhang XF, et al. Chronic aerobic exercise training attenuates aortic stiffening and endothelial dysfunction through preserving aortic mitochondrial function in aged rats. Exp Gerontol. 2014;56:37-44.
[41] Yu H, Xu H, Liu X, et al. Superoxide Mediates Depressive Effects Induced by Hydrogen Sulfide in Rostral Ventrolateral Medulla of Spontaneously Hypertensive Rats. Oxid Med Cell Longev. 2015; 2015:927686.
[42] Sun Y, Huang Y, Zhang R, et al. Hydrogen sulfide upregulates KATP channel expression in vascular smooth muscle cells ofspontaneously hypertensive rats. J Mol Med (Berl). 2015;93(4):439-455.
[43] Sun L, Jin H, Sun L, et al. Hydrogen sulfide alleviates myocardial collagen remodeling in association with inhibition of TGF-β/Smad signaling pathway in spontaneously hypertensive rats. Mol Med. 2015;20: 503-515.
[44] Sikora M, Drapala A, Ufnal M. Exogenous hydrogen sulfide causes different hemodynamic effects in normotensive andhypertensive rats via neurogenic mechanisms. Pharmacol Rep. 2014;66(5):751-758.