Semin Reprod Med 2009; 27(4): 338-345
DOI: 10.1055/s-0029-1225262
© Thieme Medical Publishers

Autonomic Regulation of Blood Pressure in Menopause

Wanpen Vongpatanasin1
  • 1Department of Internal Medicine, Hypertension Division, University of Texas Southwestern Medical Center, Dallas, Texas
Weitere Informationen

Publikationsverlauf

Publikationsdatum:
15. Juni 2009 (online)

ABSTRACT

A large body of evidence indicates a major influence of sex hormones, particularly estrogen, on autonomic regulation of blood pressure (BP). The sympathetic nervous system is now widely recognized as a major regulator of BP homeostasis and contributor to pathogenesis of hypertension in humans. Menopause is accompanied by an accelerated age-related rise in sympathetic nerve activity (SNA). Mechanisms underlying sympathetic activation in menopause are unknown but may be related to impaired central modulation of baroreflex function or direct inhibitory influence of estrogen on SNA. Menopause is also accompanied by enhanced α-adrenergic peripheral vasoconstriction both at rest and during exercise. In ovariectomized rats, reduced nitric oxide release from the skeletal muscle caused by estrogen deficiency contributes to augmented sympathetic vasoconstriction during muscle contraction. The alteration in central autonomic regulation coupled with enhanced vascular adrenergic sensitivity may be responsible for elevation in resting BP and exaggerated pressor responses to exercise and mental stress in postmenopausal women.

REFERENCES

  • 1 Cutler J A, Sorlie P D, Wolz M, Thom T, Fields L E, Roccella E J. Trends in hypertension prevalence, awareness, treatment, and control rates in United States adults between 1988-1994 and 1999-2004.  Hypertension. 2008;  52 818-827
  • 2 Zanchetti A, Facchetti R, Cesana G C, Modena M G, Pirrelli A, Sega R. SIMONA participants . Menopause-related blood pressure increase and its relationship to age and body mass index: the SIMONA epidemiological study.  J Hypertens. 2005;  23 2269-2276
  • 3 Staessen J, Bulpitt C J, Fagard R, Lijnen P, Amery A. The influence of menopause on blood pressure.  J Hum Hypertens. 1989;  3 427-433
  • 4 Owens J F, Stoney C M, Matthews K A. Menopausal status influences ambulatory blood pressure levels and blood pressure changes during mental stress.  Circulation. 1993;  88 2794-2802
  • 5 Staessen J A, Ginocchio G, Thijs L, Fagard R. Conventional and ambulatory blood pressure and menopause in a prospective population study.  J Hum Hypertens. 1997;  11 507-514
  • 6 Bunker C H, Wing R R, Mallinger A G, Becker D J, Matthews K A, Kuller L H. Cross-sectional and longitudinal relationship of sodium-lithium countertransport to insulin, obesity and blood pressure in healthy perimenopausal women.  J Hum Hypertens. 1991;  5 381-392
  • 7 Mercuro G, Zoncu S, Saiu F, Mascia M, Melis G B, Rosano G M. Menopause induced by oophorectomy reveals a role of ovarian estrogen on the maintenance of pressure homeostasis.  Maturitas. 2004;  47 131-138
  • 8 Sherwood A, Thurston R, Steffen P, Blumenthal J A, Waugh R A, Hinderliter A L. Blunted nighttime blood pressure dipping in postmenopausal women.  Am J Hypertens. 2001;  14(8 Pt 1) 749-754
  • 9 Schillaci G, Verdecchia P, Borgioni C, Ciucci A, Porcellati C. Early cardiac changes after menopause.  Hypertension. 1998;  32 764-769
  • 10 Staessen J A, Thijs L, Fagard R Systolic Hypertension in Europe Trial Investigators et al. Predicting cardiovascular risk using conventional vs ambulatory blood pressure in older patients with systolic hypertension.  JAMA. 1999;  282 539-546
  • 11 Gravholt C H, Naeraa R W, Nyholm B et al.. Glucose metabolism, lipid metabolism, and cardiovascular risk factors in adult Turner's syndrome. The impact of sex hormone replacement.  Diabetes Care. 1998;  21 1062-1070
  • 12 Gravholt C H, Hansen K W, Erlandsen M, Ebbehøj E, Christiansen J S. Nocturnal hypertension and impaired sympathovagal tone in Turner syndrome.  J Hypertens. 2006;  24 353-360
  • 13 Simonian S X, Delaleu B, Caraty A, Herbison A E. Estrogen receptor expression in brainstem noradrenergic neurons of the sheep.  Neuroendocrinology. 1998;  67 392-402
  • 14 Wang G, Drake C T, Rozenblit M et al.. Evidence that estrogen directly and indirectly modulates C1 adrenergic bulbospinal neurons in the rostral ventrolateral medulla.  Brain Res. 2006;  1094 163-178
  • 15 Saleh M C, Connell B J, Saleh T M. Autonomic and cardiovascular reflex responses to central estrogen injection in ovariectomized female rats.  Brain Res. 2000;  879 105-114
  • 16 He X R, Wang W, Crofton J T, Share L. Effects of 17beta-estradiol on sympathetic activity and pressor response to phenylephrine in ovariectomized rats.  Am J Physiol. 1998;  275(4 Pt 2) R1202-R1208
  • 17 Pamidimukkala J, Taylor J A, Welshons W V, Lubahn D B, Hay M. Estrogen modulation of baroreflex function in conscious mice.  Am J Physiol Regul Integr Comp Physiol. 2003;  284 R983-R989
  • 18 Saleh T M, Connell B J. 17β-estradiol modulates baroreflex sensitivity and autonomic tone of female rats.  J Auton Nerv Syst. 2000;  80 148-161
  • 19 Mohamed M K, El-Mas M M, Abdel-Rahman A A. Estrogen enhancement of baroreflex sensitivity is centrally mediated.  Am J Physiol. 1999;  276(4 Pt 2) R1030-R1037
  • 20 Pamidimukkala J, Xue B, Newton L G, Lubahn D B, Hay M. Estrogen receptor-alpha mediates estrogen facilitation of baroreflex heart rate responses in conscious mice.  Am J Physiol Heart Circ Physiol. 2005;  288 H1063-H1070
  • 21 Narkiewicz K, Phillips B G, Kato M, Hering D, Bieniaszewski L, Somers V K. Gender-selective interaction between aging, blood pressure, and sympathetic nerve activity.  Hypertension. 2005;  45 522-525
  • 22 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(5 Pt 2) R1600-R1604
  • 23 Jones P P, Snitker S, Skinner J S, Ravussin E. Gender differences in muscle sympathetic nerve activity: effect of body fat distribution.  Am J Physiol. 1996;  270(2 Pt 1) E363-E366
  • 24 Ng A V, Callister R, Johnson D G, Seals D R. Age and gender influence muscle sympathetic nerve activity at rest in healthy humans.  Hypertension. 1993;  21 498-503
  • 25 Hogarth A J, Mackintosh A F, Mary D A. Gender-related differences in the sympathetic vasoconstrictor drive of normal subjects.  Clin Sci (Lond). 2007;  112 353-361
  • 26 Ettinger S M, Silber D H, Collins B G et al.. Influences of gender on sympathetic nerve responses to static exercise.  J Appl Physiol. 1996;  80 245-251
  • 27 Sverrisdóttir Y B, Mogren T, Kataoka J, Janson P O, Stener-Victorin E. Is polycystic ovary syndrome associated with high sympathetic nerve activity and size at birth?.  Am J Physiol Endocrinol Metab. 2008;  294 E576-E581
  • 28 Chen M J, Yang W S, Yang J H, Chen C L, Ho H N, Yang Y S. Relationship between androgen levels and blood pressure in young women with polycystic ovary syndrome.  Hypertension. 2007;  49 1442-1447
  • 29 Davison S L, Bell R, Donath S, Montalto J G, Davis S R. Androgen levels in adult females: changes with age, menopause, and oophorectomy.  J Clin Endocrinol Metab. 2005;  90 3847-3853
  • 30 Spencer J B, Klein M, Kumar A, Azziz R. The age-associated decline of androgens in reproductive age and menopausal black and white women.  J Clin Endocrinol Metab. 2007;  92 4730-4733
  • 31 Tanaka M, Sato M, Umehara S, Nishikawa T. Influence of menstrual cycle on baroreflex control of heart rate: comparison with male volunteers.  Am J Physiol Regul Integr Comp Physiol. 2003;  285 R1091-R1097
  • 32 Ward G R, Abdel-Rahman A A. Effect of testosterone replacement or duration of castration on baroreflex bradycardia in conscious rats.  BMC Pharmacol. 2005;  5 9
  • 33 El-Mas M M, Afify E A, Mohy El-Din M M, Omar A G, Sharabi F M. Testosterone facilitates the baroreceptor control of reflex bradycardia: role of cardiac sympathetic and parasympathetic components.  J Cardiovasc Pharmacol. 2001;  38 754-763
  • 34 Sudhir K, Elser M D, Jennings G L, Komesaroff P A. Estrogen supplementation decreases norepinephrine-induced vasoconstriction and total body norepinephrine spillover in perimenopausal women.  Hypertension. 1997;  30 1538-1543
  • 35 Vongpatanasin W, Tuncel M, Mansour Y, Arbique D, Victor R G. Transdermal estrogen replacement therapy decreases sympathetic activity in postmenopausal women.  Circulation. 2001;  103 2903-2908
  • 36 Weitz G, Elam M, Born J, Fehm H L, Dodt C. Postmenopausal estrogen administration suppresses muscle sympathetic nerve activity.  J Clin Endocrinol Metab. 2001;  86 344-348
  • 37 Hunt B E, Taylor J A, Hamner J W, Gagnon M, Lipsitz L A. Estrogen replacement therapy improves baroreflex regulation of vascular sympathetic outflow in postmenopausal women.  Circulation. 2001;  103 2909-2914
  • 38 O'Sullivan A J, Crampton L J, Freund J, Ho K KY. The route of estrogen replacement therapy confers divergent effects on substrate oxidation and body composition in postmenopausal women.  J Clin Invest. 1998;  102 1035-1040
  • 39 Duanmu Z, Lapanowski K, Dunbar J C. Insulin-like growth factor-I decreases sympathetic nerve activity: the effect is modulated by glycemic status.  Proc Soc Exp Biol Med. 1997;  216 93-97
  • 40 Sverrisdóttir Y B, Johannsson G, Jungersten L, Wallin B G, Elam M. Is the somatotropic axis related to sympathetic nerve activity in healthy ageing men?.  J Hypertens. 2001;  19 2019-2024
  • 41 Sverrisdóttir Y B, Elam M, Caidahl K, Söderling A S, Herlitz H, Johannsson G. The effect of growth hormone (GH) replacement therapy on sympathetic nerve hyperactivity in hypopituitary adults: a double-blind, placebo-controlled, crossover, short-term trial followed by long-term open GH replacement in hypopituitary adults.  J Hypertens. 2003;  21 1905-1914
  • 42 Scherrer U, Randin D, Tappy L, Vollenweider P, Jéquier E, Nicod P. Body fat and sympathetic nerve activity in healthy subjects.  Circulation. 1994;  89 2634-2640
  • 43 Nair G V, Chaput L A, Vittinghoff E, Herrington D M. Heart and Estrogen/Progestin Replacement Study Investigators . Pulse pressure and cardiovascular events in postmenopausal women with coronary heart disease.  Chest. 2005;  127 1498-1506
  • 44 Rossouw J E, Anderson G L, Prentice R L Writing Group for the Women's Health Initiative Investigators et al. Risks and benefits of estrogen plus progestin in healthy postmenopausal women: principal results from the Women's Health Initiative randomized controlled trial.  JAMA. 2002;  288 321-333
  • 45 Anderson G L, Limacher M, Assaf A R Women's Health Initiative Steering Committee et al. Effects of conjugated equine estrogen in postmenopausal women with hysterectomy: the Women's Health Initiative randomized controlled trial.  JAMA. 2004;  291 1701-1712
  • 46 Ashraf M S, Vongpatanasin W. Estrogen and hypertension.  Curr Hypertens Rep. 2006;  8 368-376
  • 47 Cherney A, Edgell H, Krukoff T L. NO mediates effects of estrogen on central regulation of blood pressure in restrained, ovariectomized rats.  Am J Physiol Regul Integr Comp Physiol. 2003;  285 R842-R849
  • 48 Morimoto K, Kurahashi Y, Shintani-Ishida K et al.. Estrogen replacement suppresses stress-induced cardiovascular responses in ovariectomized rats.  Am J Physiol Heart Circ Physiol. 2004;  287 H1950-H1956
  • 49 Ueyama T, Tanioku T, Nuta J et al.. Estrogen alters c-Fos response to immobilization stress in the brain of ovariectomized rats.  Brain Res. 2006;  1084 67-79
  • 50 Gerrits M, Grootkarijn A, Bekkering B F, Bruinsma M, Den Boer J A, Ter Horst G J. Cyclic estradiol replacement attenuates stress-induced c-Fos expression in the PVN of ovariectomized rats.  Brain Res Bull. 2005;  67 147-155
  • 51 Thomas G D, Zhang W, Victor R G. Nitric oxide deficiency as a cause of clinical hypertension: promising new drug targets for refractory hypertension.  JAMA. 2001;  285 2055-2057
  • 52 Zhang K, Patel K P. Effect of nitric oxide within the paraventricular nucleus on renal sympathetic nerve discharge: role of GABA.  Am J Physiol. 1998;  275(3 Pt 2) R728-R734
  • 53 Gingerich S, Krukoff T L. Estrogen in the paraventricular nucleus attenuates L-glutamate-induced increases in mean arterial pressure through estrogen receptor beta and NO.  Hypertension. 2006;  48 1130-1136
  • 54 Gingerich S, Krukoff T L. Estrogen modulates endothelial and neuronal nitric oxide synthase expression via an estrogen receptor beta-dependent mechanism in hypothalamic slice cultures.  Endocrinology. 2005;  146 2933-2941
  • 55 Lindheim S R, Legro R S, Bernstein L et al.. Behavioral stress responses in premenopausal and postmenopausal women and the effects of estrogen.  Am J Obstet Gynecol. 1992;  167 1831-1836
  • 56 Green J S, Stanforth P R, Gagnon J et al.. Menopause, estrogen, and training effects on exercise hemodynamics: the HERITAGE study.  Med Sci Sports Exerc. 2002;  34 74-82
  • 57 Sung B H, Ching M, Izzo Jr J L, Dandona P, Wilson M F. Estrogen improves abnormal norepinephrine-induced vasoconstriction in postmenopausal women.  J Hypertens. 1999;  17 523-528
  • 58 Kajantie E, Phillips D I. The effects of sex and hormonal status on the physiological response to acute psychosocial stress.  Psychoneuroendocrinology. 2006;  31 151-178
  • 59 Komesaroff P A, Esler M D, Sudhir K. Estrogen supplementation attenuates glucocorticoid and catecholamine responses to mental stress in perimenopausal women.  J Clin Endocrinol Metab. 1999;  84 606-610
  • 60 Menozzi R, Cagnacci A, Zanni A L, Bondi M, Volpe A, Del Rio G. Sympathoadrenal response of postmenopausal women prior and during prolonged administration of estradiol.  Maturitas. 2000;  34 275-281
  • 61 Du X J, Dart A M, Riemersma R A, Oliver M F. Sex difference in presynaptic adrenergic inhibition of norepinephrine release during normoxia and ischemia in the rat heart.  Circ Res. 1991;  68 827-835
  • 62 Del Rio G, Verlardo A, Zizzo G, Marrama P, Della Casa L. Sex differences in catecholamine response to clonidine.  Int J Obes Relat Metab Disord. 1993;  17 465-469
  • 63 Del Rio G, Menozzi R, Della Casa L et al.. Alpha-2 adrenergic activity in perimenopausal women.  J Endocrinol Invest. 1997;  20 603-610
  • 64 Piletz J E, Halbreich U. Imidazoline and alpha(2a)-adrenoceptor binding sites in postmenopausal women before and after estrogen replacement therapy.  Biol Psychiatry. 2000;  48 932-939
  • 65 Zhu Y, Bian Z, Lu P et al.. Abnormal vascular function and hypertension in mice deficient in estrogen receptor beta.  Science. 2002;  295 505-508
  • 66 Freedman R R, Sabharwal S C, Desai N. Sex differences in peripheral vascular adrenergic receptors.  Circ Res. 1987;  61 581-585
  • 67 Moreau K L, Donato A J, Tanaka H, Jones P P, Gates P E, Seals D R. Basal leg blood flow in healthy women is related to age and hormone replacement therapy status.  J Physiol. 2003;  547(Pt 1) 309-316
  • 68 Smith E G, Voyles W F, Kirby B S, Markwald R R, Dinenno F A. Ageing and leg postjunctional alpha-adrenergic vasoconstrictor responsiveness in healthy men.  J Physiol. 2007;  582(Pt 1) 63-71
  • 69 Passmore J C, Joshua I G, Rowell P P, Tyagi S C, Falcone J C. Reduced alpha adrenergic mediated contraction of renal preglomerular blood vessels as a function of gender and aging.  J Cell Biochem. 2005;  96 672-681
  • 70 Parker B A, Smithmyer S L, Pelberg J A, Mishkin A D, Proctor D N. Sex-specific influence of aging on exercising leg blood flow.  J Appl Physiol. 2008;  104 655-664
  • 71 Hansen J, Thomas G D, Jacobsen T N, Victor R G. Muscle metaboreflex triggers parallel sympathetic activation in exercising and resting human skeletal muscle.  Am J Physiol. 1994;  266(6 Pt 2) H2508-H2514
  • 72 Remensnyder J P, Mitchell J H, Sarnoff S J. Functional sympatholysis during muscular activity. Observations on influence of carotid sinus on oxygen uptake.  Circ Res. 1962;  11 370-380
  • 73 Rosenmeier J B, Dinenno F A, Fritzlar S J, Joyner M J. alpha1- and alpha2-adrenergic vasoconstriction is blunted in contracting human muscle.  J Physiol. 2003;  547(Pt 3) 971-976
  • 74 Wray D W, Fadel P J, Smith M L, Raven P, Sander M. Inhibition of alpha-adrenergic vasoconstriction in exercising human thigh muscles.  J Physiol. 2004;  555(Pt 2) 545-563
  • 75 Fadel P J, Zhao W, Thomas G D. Impaired vasomodulation is associated with reduced neuronal nitric oxide synthase in skeletal muscle of ovariectomized rats.  J Physiol. 2003;  549(Pt 1) 243-253
  • 76 Fadel P J, Wang Z, Watanabe H, Arbique D, Vongpatanasin W, Thomas G D. Augmented sympathetic vasoconstriction in exercising forearms of postmenopausal women is reversed by oestrogen therapy.  J Physiol. 2004;  561(Pt 3) 893-901
  • 77 Lloyd-Jones D M, Evans J C, Levy D. Hypertension in adults across the age spectrum: current outcomes and control in the community.  JAMA. 2005;  294 466-472

Wanpen VongpatanasinM.D. 

University of Texas Southwestern Medical Center

5323 Harry Hines Blvd., U9.400, Dallas, TX 75390-8586

eMail: wanpen.vongpatanasin@utsouthwestern.edu

    >