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The effect of gender on the sympathetic nerve hyperactivity of essential hypertension

Journal of Human Hypertension volume 21, pages 239–245 (2007)Cite this article

Abstract

We planned to determine whether or not there is a difference in the level of muscle sympathetic nerve activity (MSNA) between hypertensive women and hypertensive men. Sympathetic activation of essential hypertension (EHT) has been associated with increased cardiovascular events, which are known to be less likely to occur in women than in men. Normal women have been reported to have less sympathetic nerve activity than men, but no reported data are available regarding gender differences in sympathetic activity in hypertensive subjects. We examined 36 patients with untreated and uncomplicated EHT comprising 18 women and 18 men, and 36 normal controls comprising 18 women and 18 men. MSNA was quantified as the mean frequency of single units and as multiunit bursts using the technique of microneurography. The hypertensive groups had greater sympathetic nerve activity than the control groups. Female hypertensives had lower (P<0.001) single unit hyperactivity (56±1.7 impulses/100 cardiac beats) than male hypertensives (72±1.7 impulses/100 cardiac beats). Normotensive females had lower (P<0.01) single unit activity (42±3.6 impulses/100 cardiac beats) than normotensive males (56±4.6 impulses/100 cardiac beats). Similar results were obtained for the frequency of multiunit burst activity. Hypertension in women is associated with a lower level of central sympathetic hyperactivity than in men. It is suggested that this may at least partly explain the observed lower hypertension-related cardiovascular events in women than in men. In addition, the findings may have implications for gender-specific management of hypertension.

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References

  1. Folkow B . Physiological aspect of primary hypertension. Physiol Rev 1982; 62: 347–504.

    Article  CAS  Google Scholar 

  2. Julius S, Nesbitt S . Sympathetic overactivity in hypertension. A moving target. Am J Hypertens 1996; 9: 113s–120s.

    Article  CAS  Google Scholar 

  3. Julius S . Effect of sympathetic overactivity on cardiovascular prognosis in hypertension. Eur Heart J 1998; 19 (Suppl F): F14–F18.

    PubMed  Google Scholar 

  4. Grassi G . Role of the sympathetic nervous system in human hypertension. J Hypertens 1998; 16: 1979–1987.

    Article  CAS  Google Scholar 

  5. Jennings GL . Noradrenaline spillover and microneurography measurements in patients with primary hypertension. J Hypertens 1998; 16 (Suppl): S35–S38.

    CAS  Google Scholar 

  6. Greenwood JP, Stoker JB, Mary DASG . Single unit sympathetic discharge: quantitative assessment in human hypertensive disease. Circulation 1999; 100: 1305–1310.

    Article  CAS  Google Scholar 

  7. Mancia G, Grassi G, Giannattasio C, Seravalle G . Sympathetic activation in the pathogenesis of hypertension and progression of organ damage. Hypertension 1999; 34: 724–728.

    Article  CAS  Google Scholar 

  8. Esler M . The sympathetic system and hypertension. Am J Hypertens 2000; 13: 99S–105S.

    Article  CAS  Google Scholar 

  9. Lewington S, Clarke R, Qizilbash N, Peto R, Collins R, Prospective Studies Collaboration. Age-specific relevance of usual blood pressure to vascular mortality: a meta-analysis of individual data for one million adults in 61 prospective studies. Lancet 2002; 360: 1903–1913.

    Article  Google Scholar 

  10. Robitaille NM . Hypertension in women. Can J Cardiol 1996; 12 (Suppl D): 6D–8D.

    PubMed  Google Scholar 

  11. Lloyd-Jones DM, Leip EP, Larson MG, Vasan RS, Levy D . Novel approach to examining first cardiovascular events after hypertension onset. Hypertension 2005; 45: 39–45.

    Article  CAS  Google Scholar 

  12. Isles CG, Hole DJ, Hawthorne VM, Lever AF . Relation between coronary risk and coronary mortality in women of the Renfrew and Paisley survey: comparison with men. Lancet 1992; 339: 702–706.

    Article  CAS  Google Scholar 

  13. Safar ME, Smulyan H . Hypertension in women. Am J Hypertens 2004; 17: 82–87.

    Article  Google Scholar 

  14. Mary DA, Stoker JB . The activity of single vasoconstrictor nerve units in hypertension. Acta Physiol Scand 2003; 177: 367–376.

    Article  CAS  Google Scholar 

  15. Ng AV, Callister R, Johnson DG, Seals DR . Age and gender influence muscle sympathetic nerve activity at rest in healthy humans. Hypertension 1993; 21: 498–503.

    Article  CAS  Google Scholar 

  16. Jones PP, Snitker S, Skinner JS, Ravussin E . Gender differences in muscle sympathetic nerve activity: effect of body fat distribution. Am J Physiol 1996; 270: E363–E366.

    CAS  PubMed  Google Scholar 

  17. Matsukawa T, Sugiyama Y, Watanabe T, Kobayashi F, Mano T . Gender difference in age-related changes in muscle sympathetic nerve activity in healthy subjects. Am J Physiol 1998; 275: R1600–R1604.

    CAS  Google Scholar 

  18. Shoemaker JK, Hogeman CS, Khan M, Kimmerly DS, Sinoway LI . Gender affects sympathetic and hemodynamic response to postural stress. Am J Physiol Heart Circ Physiol 2001; 281: H2028–H2035.

    Article  CAS  Google Scholar 

  19. Narkiewicz K, Phillips BG, Kato M, Hering D, Bieniaszewski L, Somers VK . Gender-selective interaction between aging, blood pressure, and sympathetic nerve activity. Hypertension 2005; 45: 522–525.

    Article  CAS  Google Scholar 

  20. Tank J, Diedrich A, Szczech E, Luft FC, Jordan J . Baroreflex regulation of heart rate and sympathetic vasomotor tone in women and men. Hypertension 2005; 45: 1159–1164.

    Article  CAS  Google Scholar 

  21. Fu Q, Witkowski S, Okazaki K, Levine BD . Effects of gender and hypovolemia on sympathetic neural responses to orthostatic stress. Am J Physiol Regul Integr Comp Physiol 2005; 289: R109–R116.

    Article  CAS  Google Scholar 

  22. Chobanian AV, Bakris GL, Black HR, Cushman WC, Green LA, Izzo Jr JL et al. National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure. National Heart, Lung, and Blood Institute; National High Blood Pressure Education Program Coordinating Committee. Seventh report of the Joint National Committee on prevention, detection, evaluation, and treatment of high blood pressure. Hypertension 2003; 42: 1206–1252.

    Article  CAS  Google Scholar 

  23. Williams B, Poulter NR, Brown MJ, Davis M, McInnes GT, Potter JF et al. British Hypertension Society. Guidelines for management of hypertension: report of the fourth working party of the British Hypertension Society, 2004-BHS IV. J Human Hypertens 2004; 18: 139–185.

    Article  CAS  Google Scholar 

  24. Macefield VG, Wallin BG, Vallbo AB . The discharge behaviour of single vasoconstrictor motoneurones in human muscle nerves. J Physiol (London) 1994; 481: 799–809.

    Article  CAS  Google Scholar 

  25. Yamada Y, Miyajima E, Tochikubo O, Matsukawa T, Ishii M . Age-related changes in muscle sympathetic nerve activity in essential hypertension. Hypertension 1989; 13: 870–877.

    Article  CAS  Google Scholar 

  26. Matsukawa T, Gotoh E, Hasegawa O, Shionoiri H, Tochikubo O, Ishii M . Reduced baroreflex changes in muscle sympathetic nerve activity during blood pressure elevation in essential hypertension. J Hypertens 1991; 9: 537–542.

    Article  CAS  Google Scholar 

  27. Floras JS, Hara K . Sympathoneural and haemodynamic characteristics of young subjects with mild essential hypertension. J Hypertens 1993; 11: 647–655.

    Article  CAS  Google Scholar 

  28. Grassi G, Cattaneo BM, Seravalle G, Lanfranchi A, Mancia G . Baroreflex control of sympathetic nerve activity in essential and secondary hypertension. Hypertension 1998; 31: 68–72.

    Article  CAS  Google Scholar 

  29. Smith PA, Graham LN, Mackintosh AF, Stoker JB, Mary DA . Relationship between central sympathetic activity and stages of human hypertension. Am J Hypertens 2004; 17: 217–222.

    Article  Google Scholar 

  30. Calhoun DA, Mutinga ML, Collins AS, Wyss JM, Oparil S . Normotensive blacks have heightened sympathetic response to cold pressor test. Hypertension 1993; 22: 801–805.

    Article  CAS  Google Scholar 

  31. Anderson EA, Sinkey CA, Lawton WJ, Mark AL . Elevated sympathetic nerve activity in borderline hypertensive humans. Evidence from direct intraneural recordings. Hypertension 1989; 14: 177–183.

    Article  CAS  Google Scholar 

  32. Scherrer U, Randin D, Tappy L, Vollenweider P, Jequier E, Nicod P . Body fat and sympathetic nerve activity in healthy subjects. Circulation 1994; 89: 2634–2640.

    Article  CAS  Google Scholar 

  33. Cox HS, Kaye DM, Thompson JM, Turner AG, Jennings GL, Itsiopoulos C et al. Regional sympathetic nervous activation after a large meal in humans. Clin Sci (Colch) 1995; 89: 145–154.

    Article  CAS  Google Scholar 

  34. Fagius H, Karhuvaara S . Sympathetic activity and blood pressure increases with bladder distension in humans. Hypertension 1989; 14: 511–517.

    Article  CAS  Google Scholar 

  35. Sundlöf G, Wallin BG . Human muscle nerve sympathetic activity at rest. Relationship to blood pressure and age. J Physiol (London) 1978; 274: 621–637.

    Article  Google Scholar 

  36. Skarphedinsson JO, Elam M, Jungersten L, Wallin BG . Sympathetic nerve traffic correlates with the release of nitric oxide in humans: implications for blood pressure control. J Physiol (London) 1997; 501: 671–675.

    Article  CAS  Google Scholar 

  37. Wallin BG, Esler M, Dorward P, Eisenhofer G, Ferrier C, Westerman R et al. Simultaneous measurements of cardiac noradrenaline spillover and sympathetic outflow to skeletal muscle in humans. J Physiol (London) 1992; 453: 45–58.

    Article  CAS  Google Scholar 

  38. Wallin BG, Thompson JM, Jennings GL, Esler MD . Renal noradrenaline spillover correlates with muscle sympathetic activity in humans. J Physiol (London) 1996; 491: 881–887.

    Article  CAS  Google Scholar 

  39. Kuo TB, Lin T, Yang CC, Li CL, Chen CF, Chou P . Effect of aging on gender differences in neural control of heart rate. Am J Physiol 1999; 277: H2233–H2239.

    CAS  PubMed  Google Scholar 

  40. Huikuri HV, Pikkujamsa SM, Airaksinen KE, Ikaheimo MJ, Rantala AO, Kauma H et al. Sex-related differences in autonomic modulation of heart rate in middle-aged subjects. Circulation 1996; 94: 122–125.

    Article  CAS  Google Scholar 

  41. Christou DD, Jones PP, Jordan J, Diedrich A, Robertson D, Seals DR . Women have lower tonic autonomic support of arterial blood pressure and less effective baroreflex buffering than men. Circulation 2005; 111: 494–498.

    Article  Google Scholar 

  42. Huggett RJ, Scott EM, Gilbey SG, Stoker JB, Mackintosh AF, Mary DASG . Impact of type 2 diabetes mellitus on sympathetic neural mechanisms in hypertension. Circulation 2003; 108: 3097–3101.

    Article  CAS  Google Scholar 

  43. Huggett RJ, Burns J, Mackintosh AF, Mary DASG . Sympathetic neural activation in nondiabetic metabolic syndrome and its further augmentation by hypertension. Hypertension 2004; 44: 847–852.

    Article  CAS  Google Scholar 

  44. Haynes WG, Sivitz WI, Morgan DA, Walsh SA, Mark AL . Sympathetic and cardiorenal actions of leptin. Hypertension 1997; 30: 619–623.

    Article  CAS  Google Scholar 

  45. Narkiewicz K, Kato M, Phillips BG, Pesek CA, Choe I, Winnicki M et al. Leptin interacts with heart rate but not sympathetic nerve traffic in healthy male subjects. J Hypertens 2001; 19: 1089–1094.

    Article  CAS  Google Scholar 

  46. Alvarez GE, Ballard TP, Beske SD, Davy KP . Subcutaneous obesity is not associated with sympathetic neural activation. Am J Physiol Heart Circ Physiol 2004; 287: H414–H418.

    Article  CAS  Google Scholar 

  47. Ettinger SM, Silber DH, Gray KS, Smith MB, Yang QX, Kunselman AR et al. Effects of the ovarian cycle on sympathetic neural outflow during static exercise. J Appl Physiol 1998; 85: 2075–2081.

    Article  CAS  Google Scholar 

  48. Minson CT, Halliwill JR, Young TM, Joyner MJ . Influence of the menstrual cycle on sympathetic activity, baroreflex sensitivity, and vascular transduction in young women. Circulation 2000; 101: 862–868.

    Article  CAS  Google Scholar 

  49. Hinojosa-Laborde C, Chapa I, Lange D, Haywood JR . Gender differences in sympathetic nervous system regulation. Clin Exp Pharmacol Physiol 1999; 26: 1440–1681.

    Google Scholar 

  50. Barnett SR, Morin RJ, Kiely DK, Gagnon M, Azhar G, Knight EL et al. Effects of age and gender on autonomic control of blood pressure dynamics. Hypertension 1999; 33: 1195–1200.

    Article  CAS  Google Scholar 

  51. Stramba-Badiale M, Fox KM, Priori SG, Collins P, Daly C, Graham I et al. Cardiovascular diseases in women: a statement from the policy conference of the European Society of Cardiology. Eur Heart J 2006; 27: 994–1005.

    Article  Google Scholar 

  52. Grassi G, Seravalle G, Turri C, Bolla G, Mancia G . Short-versus long-term effects of different dihydropyridines on sympathetic and baroreflex function in hypertension. Hypertension 2003; 41: 558–562.

    Article  CAS  Google Scholar 

  53. Binggeli C, Corti R, Sudano I, Luscher TF, Noll G . Effects of chronic calcium channel blockade on sympathetic nerve activity in hypertension. Hypertension 2002; 39: 892–896.

    Article  CAS  Google Scholar 

  54. Struck J, Muck P, Trubger D, Handrock R, Weidinger G, Dendorfer A et al. Effects of selective angiotensin II receptor blockade on sympathetic nerve activity in primary hypertensive subjects. J Hypertens 2002; 20: 1143–1149.

    Article  CAS  Google Scholar 

  55. Grassi G, Turri C, Dell'Oro R, Stella ML, Bolla GB, Mancia G . Effect of chronic angiotensin converting enzyme inhibition on sympathetic nerve traffic and baroreflex control of the circulation in essential hypertension. J Hypertens 1998; 16: 1789–1796.

    Article  CAS  Google Scholar 

  56. Burns J, Mary DASG, Mackintosh AF, Ball SG, Greenwood JP . Arterial pressure lowering effect of chronic atenolol therapy in hypertension and vasoconstrictor sympathetic drive. Hypertension 2004; 44: 454–458.

    Article  CAS  Google Scholar 

  57. Greenwood JP, Scott EM, Stoker JB, Mary DA . Chronic I(1)-imidazoline agonism: sympathetic mechanisms in hypertension. Hypertension 2000; 35: 1264–1269.

    Article  CAS  Google Scholar 

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Acknowledgements

We thank Mr Jeff Bannister and Mrs Julie Corrigan for technical assistance. This work was sponsored by the British Heart Foundation (Grant No: FS/04/085).

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  1. The Department of Cardiology, St James's University Hospital, Leeds, UK

    A J Hogarth, A F Mackintosh & D A S G Mary

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  1. A J Hogarth
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Correspondence to A J Hogarth.

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Hogarth, A., Mackintosh, A. & Mary, D. The effect of gender on the sympathetic nerve hyperactivity of essential hypertension. J Hum Hypertens 21, 239–245 (2007). https://doi.org/10.1038/sj.jhh.1002132

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