交感神经系统亢进在高血压疾病发生发展中的作用

doi:10.3969/j.issn.1674-490X.2019.06.004

摘要/Abstract

摘要： 高血压的交感神经源性机制是高血压发生机制的重要学说,通过对大量临床研究数据的收集,探讨交感神经系统活性增强在临床高血压发生、发展以及治疗过程中所发挥的作用,概述交感神经对心血管功能调节的前沿知识,阐述干预交感神经系统及治疗高血压的新疗法。

关键词: 高血压, 交感神经功能亢进, 动脉压力感受器, 肾素-血管紧张素系统, 新疗法

Abstract: The sympathetic neurogenic mechanism of hypertension is an important theory of the mechanism of hypertension. Through the collection of a large number of clinical research data, the role of sympathetic nervous system activity enhancement in the occurrence, development and treatment of hypertension are discussed. It also outlines the frontier knowledge of sympathetic nerve regulation of cardiovascular function, and describes new therapies for intervention in the sympathetic nervous system and treatment of hypertension.

Key words: hypertension, sympathetic hyperfunction, arterial baroreceptor, renin-angiotensin system, new therapy

中图分类号:

问慧娟,贾静,赵宇菲,李娜. 交感神经系统亢进在高血压疾病发生发展中的作用[J]. 医学研究与教育, 2019, 36(6): 21-27.

参考文献

[1] 娄荷清, 董宗美, 张盼, 等. 我国高血压患病现状及可改变危险因素研究新进展[J]. 中国慢性病预防与控制, 2017, 25(4): 319-322. DOI: 10.16386/j.cjpccd.issn.1004-6194.2017.04.024.
[2] DIBONA G F. Sympathetic nervous system and hypertension[J]. Hypertension, 2013, 61(3): 556-560. DOI: 10.1161/hypertensionaha.111.00633.
[3] GUYENET P G. The sympathetic control of blood pressure[J]. Nat Rev Neurosci, 2006, 7(5): 335-346. DOI: 10.1038/nrn1902.
[4] GRASSI G, MARK A, ESLER M. The sympathetic nervous system alterations in human hypertension[J]. Circ Res, 2015, 116(6): 976-990. DOI: 10.1161/circresaha.116.303604.
[5] WESTFALL D P, TODOROV L D, MIHAYLOVA-TODOROVA S T. ATP as a cotransmitter in sympathetic nerves and its inactivation by releasable enzymes[J]. J Pharmacol Exp Ther, 2002, 303(2): 439-444. DOI: 10.1124/jpet.102.035113.
[6] CHEN Y Y, LV J, XUE X Y, et al. Effects of sympathetic histamine on vasomotor responses of blood vessels in rabbit ear to electrical stimulation[J]. Neurosci Bull, 2010, 26(3): 219-224. DOI: 10.1007/s12264-010-1126-6.
[7] LOHMEIER T E, DWYER T M, IRWIN E D, et al. Prolonged activation of the baroreflex abolishes obesity-induced hypertension[J]. Hypertension, 2007, 49(6): 1307-1314. DOI: 10.1161/hypertensionaha.107.087874.
[8] ROKOSH D G, SIMPSON P C. Knockout of the 1A/C-adrenergic receptor subtype: The 1A/C is expressed in resistance arteries and is required to maintain arterial blood pressure[J]. Proc Natl Acad Sci U S A, 2002, 99(14): 9474-9479. DOI: 10.1073/pnas.132552699.
[9] CHRUSCINSKI A J, ROHRER D K, SCHAUBLE E, et al. Targeted disruption of the β2 adrenergic receptor gene[J]. J Biol Chem, 1999, 274(24): 16694-16700. DOI: 10.1074/jbc.274.24.16694.
[10] JOHNS E J, KOPP U C, DIBONA G F. Neural control of renal function[J]. Compr hysiol, 2011, 1(2): 731-767. DOI: 10. 1002/cphy. c100043.
[11] ILIESCU R, IRWIN E D, GEORGAKOPOULOS D, et al. Renal responses to chronic suppression of central sympathetic outflow[J]. Hypertension, 2012, 60(3): 749-756. DOI: 10.1161/hypertensionaha.112.193607.
[12] KOPP U C, DIBONA G F. Neural regulation of renin secretion[J]. Semin Nephrol, 1993, 13(6): 543-551.
[13] DAMPNEY R, COLEMAN M J, FONTES M, et al. Central mechanisms underlying short- and long-term regulation of the cardiovascular system[J]. Clin Exp Pharmacol Physiol, 2002, 29(4): 261-268. DOI: 10.1046/j.1440-1681.2002.03640.x.
[14] OSBORN J W. Hypothesis: set-points and long-term control of arterial pressure. A theoretical argument for a long-term arterial pressure control system in the brain rather than the kidney[J]. Clin Exp Pharmacol Physiol, 2005, 32(5/6): 384-393. DOI: 10. 1111/j.1440-1681.2005.04200.x.
[15] THRASHER T N. Baroreceptors and the long-term control of blood pressure[J]. Exp Physiol, 2004, 89(4): 331-335. DOI: 10.1113/expphysiol.2004.027441.
[16] THRASHER T N. Arterial baroreceptor input contributes to long-term control of blood pressure[J]. Current Science Inc, 2006, 8(3): 249-254. DOI: 10.1007/s11906-006-0058-z.
[17] LOHMEIER T E, ILIESCU R. The baroreflex as a long-term controller of arterial pressure[J]. Physiology, 2015, 30(2): 148-158. DOI: 10.1152/physiol.00035.2014.
[18] GOLDSTEIN D S. Plasma catecholamines and essential hypertension. An analytical review[J]. Hypertension, 1983, 5(1): 86-99. DOI: 10.1161/01.hyp.5.1.86.
[19] ESLER M, LAMBERT G, JENNINGS G. Regional norepinephrine turnover in human hypertension[J]. Clin Exp Hypertens A, 1989, 11(suppl 1): 75-89. DOI: 10.3109/10641968909045414.
[20] ANDERSON E A, SINKEY C A, LAWTON W J, et al. Elevated sympathetic nerve activity in borderline hypertensive humans. Evidence from direct intraneural recordings[J]. Hypertension, 1989, 14(2): 177-183. DOI: 10.1161/01.hyp.14.2.177.
[21] HUGGETT R J, BURNS J, MACKINTOSH A F, et al. Sympathetic neural activation in nondiabetic metabolic syndrome and its further augmentation by hypertension[J]. Hypertension, 2004, 44(6): 847-852. DOI: 10.1161/01.hyp.0000147893.08533.d8.
[22] GRASSI G, DELL'ORO R, QUARTI-TREVANO F, et al. Neuroadrenergic and reflex abnormalities in patients with metabolic syndrome[J]. Diabetologia, 2005, 48(7): 1359-1365. DOI: 10.1007/s00125-005-1798-z.
[23] GRASSI G, CATTANEO B M, SERAVALLE G, et al. Baroreflex control of sympathetic nerve activity in essential and secondary hypertension[J]. Hypertension, 1998, 31(1): 68-72. DOI: 10.1161/01.hyp.31.1.68.
[24] GRASSI G, SERAVALLE G, BERTINIERI G, et al. Sympathetic and reflex alterations in systo-diastolic and systolic hypertension of the elderly[J]. J Hypertens, 2000, 18(5): 587-593. DOI: 10.1097/00004872-200018050-00012.
[25] SMITH P A, GRAHAM L N, MACKINTOSH A F, et al. Sympathetic neural mechanisms in white-coat hypertension[J]. J Am Coll Cardiol, 2002, 40(1): 126-132. DOI: 10.1016/s0735-1097(02)01931-9.
[26] NEUMANN S, JENNINGS J, MULDOON M, et al. White-coat hypertension and autonomic nervous system dysregulation[J]. Am J Hypertens, 2005, 18(5): 584-588. DOI: 10.1016/j.amjhyper.2004.11.034.
[27] GRASSI G, SERAVALLE G, TREVANO F Q, et al. Neurogenic abnormalities in masked hypertension[J]. Hypertension, 2007, 50(3): 537-542. DOI: 10.1161/hypertensionaha.107.092528.
[28] GRASSI G, SERAVALLE G, QUARTI-TREVANO F, et al. Adrenergic, metabolic, and reflex abnormalities in reverse and extreme dipper hypertensives[J]. Hypertension, 2008, 52(5): 925-931. DOI: 10.1161/hypertensionaha.108.116368.
[29] 孙刚. 高血压左心室肥厚临床危害及治疗对策[J]. 中国实用内科杂志, 2011, 31(8): 598-599.
[30] GREENWOOD J P, SCOTT E M, STOKER J B, et al. Hypertensive left ventricular hypertrophy: relation to peripheral sympathetic drive[J]. J Am Coll Cardiol, 2001, 38(6): 1711-1717. DOI:10.1016/s0735-1097(01)01600-x.
[31] SCHLAICH M P, KAYE D M, LAMBERT E, et al. Relation between cardiac sympathetic activity and hypertensive left ventricular hypertrophy[J]. Circulation, 2003, 108(5): 560-565. DOI: 10.1161/01.cir.0000081775.72651.b6.
[32] GRASSI G, SERAVALLE G, QUARTI-TREVANO F, et al. Sympathetic and baroreflex cardiovascular control in hypertension-related left ventricular dysfunction[J]. Hypertension, 2009, 53(2): 205-209. DOI: 10.1161/hypertensionaha.108.121467.
[33] CONVERSE R L Jr, JACOBSEN T N, TOTO R D, et al. Sympathetic overactivity in patients with chronic renal failure[J]. N Engl J Med, 1992, 327(27): 1912-1918. DOI: 10.1056/nejm199212313272704.
[34] GRASSI G, QUARTI-TREVANO F, SERAVALLE G, et al. Early sympathetic activation in the initial clinical stages of chronic renal failure[J]. Hypertension, 2011, 57(4): 846-851. DOI: 10.1161/hypertensionaha.110.164780.
[35] KIELSTEIN J T, FLISER D. The past, presence and future of ADMA in nephrology[J]. Néphrologie Thérapeutique, 2007, 3(2): 47-54. DOI: 10.1016/j.nephro.2007.02.002.
[36] GRASSI G, SERAVALLE G, GHIADONI L, et al. Sympathetic nerve traffic and asymmetric dimethylarginine in chronic kidney disease[J]. Clin J Am Soc Nephrol, 2011, 6(11): 2620-2627. DOI: 10.2215/cjn.06970711.
[37] HERING D, KARA T, KUCHARSKA W, et al. High-normal blood pressure is associated with increased resting sympathetic activity but normal responses to stress tests[J]. Blood Press, 2013, 22(3): 183-187. DOI: 10.3109/08037051.2012.759689.
[38] SERAVALLE G, LONATI L, BUZZI S, et al. Sympathetic nerve traffic and baroreflex function in optimal, normal, and high-normal blood pressure states[J]. J Hypertens, 2015, 33(7): 1411-1417. DOI: 10.1097/hjh.0000000000000567.
[39] EGAN B M, STEVENS-FABRY S. Prehypertension: prevalence, health risks, and management strategies[J]. Nat Rev Cardiol, 2015, 12(5): 289-300. DOI: 10.1038/nrcardio.2015.17.
[40] PAL G K, ADITHAN C, AMUDHARAJ D, et al. Assessment of sympathovagal imbalance by spectral analysis of heart rate variability in prehypertensive and hypertensive patients in Indian population[J]. Clin Exp Hypertens, 2011, 33(7): 478-483. DOI: 10.3109/10641963.2010.549275.
[41] GRASSI G, SERAVALLE G, BRAMBILLA G, et al. Marked sympathetic activation and baroreflex dysfunction in true resistant hypertension[J]. Int J Cardiol, 2014, 177(3): 1020-1025. DOI: 10.1016/j.ijcard.2014.09.138.
[42] VLACHOPOULOS C, AZNAOURIDIS K, O'ROURKE M F, et al. Prediction of cardiovascular events and all-cause mortality with central haemodynamics: a systematic review and meta-analysis[J]. Eur Heart J, 2010, 31(15): 1865-1871. DOI: 10.1093/eurheartj/ehq024.
[43] MAHFOUD F, BÖHM M, AZIZI M, et al. Proceedings from the European clinical consensus conference for renal denervation: considerations on future clinical trial design: Figure 1[J]. Eur Heart J, 2015, 36(33): 2219-2227. DOI: 10.1093/eurheartj/ehv192.
[44] GRASSI G, SERAVALLE G, QUARTI-TREVANO F. The ‘neuroadrenergic hypothesis’ in hypertension: current evidence[J]. Exp Physiol, 2010, 95(5): 581-586. DOI: 10.1113/expphysiol.2009.047381.
[45] GRASSI G, PADMANABHAN S, MENNI C, et al. Association between ADRA1A gene and the metabolic syndrome: candidate genes and functional counterpart in the PAMELA population[J]. J Hypertens, 2011, 29(6): 1121-1127. DOI: 10.1097/hjh.0b013e328346d72c.
[46] NIELSEN S J, JEPPESEN J, TORP-PEDERSEN C, et al. Tyrosine hydroxylase polymorphism(C-824T)and hypertension: A population-based study[J]. Am J Hypertens, 2010, 23(12): 1306-1311. DOI: 10.1038/ajh.2010.165.
[47] MASUO K, KATSUYA T, FU Y, et al. Β-adrenoceptor polymorphisms relate to insulin resistance and sympathetic overactivity as early markers of metabolic disease in nonobese, normotensive individuals[J]. Am J Hypertens, 2005, 18(7): 1009-1014. DOI: 10.1016/j.amjhyper.2005.01.006.
[48] SERAVALLE G, PIPERNO A, MARIANI R, et al. Alterations in sympathetic nerve traffic in genetic haemochromatosis before and after iron depletion therapy: a microneurographic study[J]. Eur Heart J, 2016, 37(12): 988-995. DOI: 10.1093/eurheartj/ehv696.
[49] PONGRATZ G, STRAUB R H. The sympathetic nervous response in inflammation[J]. Arthritis Res Ther, 2014, 16(6): 504. DOI: 10.1186/s13075-014-0504-2.
[50] MANKIN L A. Update in hypertension therapy[J]. Med Clin N Am, 2016, 100(4): 665-693. DOI: 10.1016/j.mcna.2016.03.005.
[51] BISOGNANO J D, BAKRIS G, NADIM M K, et al. Baroreflex activation therapy lowers blood pressure in patients with resistant hypertension[J]. J Am Coll Cardiol, 2011, 58(7): 765-773. DOI: 10.1016/j.jacc.2011.06.008.
[52] 丁蕊, 刘德敏, 崔炜. 去肾交感神经术治疗顽固性高血压的研究进展[J]. 医学综述, 2016, 22(10): 1920-1923. DOI: 10.3969/j.issn. 1006-2084.2016.10.014.
[53] BHATT D L, KANDZARI D E, O'NEILL W W, et al. A controlled trial of renal denervation for resistant hypertension[J]. N Engl J Med, 2014, 370(15): 1393-1401. DOI: 10.1056/nejmoa1402670.
[54] GRASSI G, SERAVALLE G, BRAMBILLA G, et al. Blood pressure responses to renal denervation precede and are independent of the sympathetic and baroreflex effects[J]. Hypertension, 2015, 65(6): 1209-1216. DOI: 10.1161/hypertensionaha.114.04823.
[55] GRASSI G, TURRI C, DELL'ORO R, et al. Effect of chronic angiotensin converting enzyme inhibition on sympathetic nerve traffic and baroreflex control of the circulation in essential hypertension[J]. J Hypertens, 1998, 16(12): 1789-1796. DOI: 10. 1097/00004872-199816120-00012.
[56] GRASSI G, SERAVALLE G, DELL'ORO R, et al. Comparative effects of candesartan and hydrochlorothiazide on blood pressure, insulin sensitivity, and sympathetic drive in obese hypertensive individuals[J]. J Hypertens, 2003, 21(9): 1761-1769. DOI: 10.1097/00004872-200309000-00027.
[57] SERAVALLE G, BRAMBILLA G, PIZZALLA D P, et al. Differential effects of enalapril-felodipine versus enalapril-lercanidipine combination drug treatment on sympathetic nerve traffic and metabolic profile in obesity-related hypertension[J]. J Am Soc Hypertens, 2016, 10(3): 244-251. DOI: 10.1016/j.jash.2016.01.006.
[58] ZANCHETTI A, GRASSI G, MANCIA G. When should antihypertensive drug treatment be initiated and to what levels should systolic blood pressure be lowered? A critical reappraisal[J]. J Hypertens, 2009, 27(5): 923-934. DOI: 10.1097/hjh.0b013e32832aa6b5.