Short-term sympathoadrenal inhibition augments the thermogenic response to β-adrenergic receptor stimulation

Journal of Endocrinology

Volumn 206, Issue 3, 2010, Pages 307-315

  Newsom, Sean A ^a   Richards, Jennifer C ^a   Johnson, Tyler K ^a   Kuzma, Jessica N ^a   Lonac, Mark C ^a   Paxton, Roger J ^a   Rynn, Grant M ^a   Voyles, Wyatt F ^a   Bell, Christopher ^a  

^a Department of Environmental and Radiological Health Sciences   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

BETA ADRENERGIC RECEPTOR; CLONIDINE; ISOPRENALINE; NORADRENALIN; OXYGEN;

ADRENERGIC SYSTEM; ADULT; ARTICLE; BETA ADRENERGIC STIMULATION; BODY MASS; CALORIMETRY; CONTROLLED STUDY; DRUG HALF LIFE; DRUG INHIBITION; DRUG MECHANISM; ENERGY BALANCE; ENERGY EXPENDITURE; FEMALE; HEART RATE; HUMAN; LUNG GAS EXCHANGE; MALE; NORMAL HUMAN; OXYGEN CONSUMPTION; PRIORITY JOURNAL; SITTING; SKELETAL MUSCLE; SYMPATHETIC NERVE; THERMOGENESIS;

ADRENERGIC ALPHA-AGONISTS; ADRENERGIC BETA-AGONISTS; ADULT; ANALYSIS OF VARIANCE; BODY MASS INDEX; BODY TEMPERATURE REGULATION; CALORIMETRY, INDIRECT; CLONIDINE; ENERGY METABOLISM; FEMALE; HUMANS; ISOPROTERENOL; MALE; NOREPINEPHRINE; RECEPTORS, ADRENERGIC, BETA; SEDENTARY LIFESTYLE; SEX FACTORS; SYMPATHETIC NERVOUS SYSTEM;

EID: 77955630495     PISSN: 00220795     EISSN: 14796805     Source Type: Journal    
DOI: 10.1677/JOE-10-0152     Document Type: Article

References (84)

1. van Aggel-Leijssen DP, Saris WH, Homan M & van Baak MA 2001 The effect of exercise training on beta-adrenergic stimulation of fat metabolism in obese men. International Journal of Obesity and Related Metabolic Disorders 25 16-23. (doi:10.1038/sj.ijo.0801470) (Pubitemid 32142379)
2. Alvarez GE, Beske SD, Ballard TP & Davy KP 2002 Sympathetic neural activation in visceral obesity. Circulation 106 2533-2536. (doi:10.1161/01.CIR. 0000041244.79165.25)
3. van Baak MA 2001 The peripheral sympathetic nervous system in human obesity. Obesity Reviews 2 3-14. (doi:10.1046/j.1467-789x.2001.00010.x)
4. van Baak MA, Hul GB, Toubro S, Astrup A, Gottesdiener KM, DeSmet M & Saris WH 2002 Acute effect of L-796568, a novel beta 3-adrenergic receptor agonist, on energy expenditure in obese men. Clinical Pharmacology and Therapeutics 71 272-279. (doi:10.1067/mcp.2002.122527) (Pubitemid 34311456)
5. Bachman ES, Dhillon H, Zhang CY, Cinti S, Bianco AC, Kobilka BK & Lowell BB 2002 beta AR signaling required for diet-induced thermogenesis and obesity resistance. Science 297 843-845. (doi:10.1126/science.1073160) (Pubitemid 34839635)
6. Banumathi E, Sheikpranbabu S, Haribalaganesh R & Gurunathan S 2010 PEDF prevents reactive oxygen species generation and retinal endothelial cell damage at high glucose levels. Experimental Eye Research 90 89-96. (doi:10.1016/j.exer.2009.09.014)
7. Bell C, Seals DR, Monroe MB, Day DS, Shapiro LF, Johnson DG & Jones PP 2001 Tonic sympathetic support of metabolic rate is attenuated with age, sedentary lifestyle, and female sex in healthy adults. Journal of Clinical Endocrinology and Metabolism 86 4440-4444. (doi:10.1210/jc.86.9.4440) (Pubitemid 32848572)
8. Bell C, Jones PP & Seals DR 2003 Oxidative stress does not modulate metabolic rate or skeletal muscle sympathetic activity with primary aging in adult humans. Journal of Clinical Endocrinology and Metabolism 88 4950-4954. (doi:10.1210/jc.2003-030454) (Pubitemid 37357549)
9. Bell C, Day DS, Jones PP, Christou DD, Petitt DS, Osterberg K, Melby CL & Seals DR 2004 High energy flux mediates the tonically augmented beta-adrenergic support of resting metabolic rate in habitually exercising older adults. Journal of Clinical Endocrinology and Metabolism 89 3573-3578. (doi:10.1210/jc.2003-032146) (Pubitemid 38951936)
10. Bell C, Carson JM, Motte NW & Seals DR 2005 Ascorbic acid does not affect the age-associated reduction in maximal cardiac output and oxygen consumption in healthy adults. Journal of Applied Physiology 98 845-849. (doi:10.1152/japplphysiol.00790.2004) (Pubitemid 40283663)
11. Bell C, Stob NR & Seals DR 2006a Thermogenic responsiveness to β-adrenergic stimulation is augmented in exercising vs. sedentary adults: role of oxidative stress. Journal of Physiology 570 629-653. (doi:10.1113/jphysiol.2005.098756)
12. Bell C, Stob NR & Seals DR 2006b Thermogenic responsiveness to nonspecific beta-adrenergic stimulation is not related to genetic variation in codon 16 of the beta2-adrenergic receptor. American Journal of Physiology. Endocrinology and Metabolism 290 E703-E707. (doi:10.1152/ajpendo.00411.2005)
13. Blaak EE, van Baak MA, Kemerink GJ, Pakbiers MT, Heidendal GA & Saris WH1994 Beta-adrenergic stimulation of energy expenditure and forearm skeletal muscle metabolism in lean and obese men. American Journal of Physiology 267 E306-E315.
14. Blaak EE, van Baak MA, Kester AD & Saris WH 1995 Beta-adrenergically mediated thermogenic and heart rate responses: effect of obesity and weight loss. Metabolism 44 520-524. (doi:10.1016/0026-0495(95)90061-6)
15. Booth FW, Laye MJ, Lees SJ, Rector RS & Thyfault JP 2008 Reduced physical activity and risk of chronic disease: the biology behind the consequences. European Journal of Applied Physiology 102 381-390. (doi:10.1007/s00421-007-0606-5)
16. Borg GA 1982 Psychophysical bases of perceived exertion. Medicine and Science in Sports and Exercise 14 377-381.
17. Christou DD & Seals DR 2008 Decreased maximal heart rate with aging is related to reduced b-adrenergic responsiveness but is largely explained by a reduction in intrinsic heart rate. Journal of Applied Physiology 105 24-29. (doi:10.1152/japplphysiol.90401.2008)
18. Church T 2009 The low-fitness phenotype as a risk factor: more than just being sedentary? Obesity 17 S39-S42. (doi:10.1038/oby.2009.387)
19. Crowe S, Wu LE, Economou C, Turpin SM, Matzaris M, Hoehn KL, Hevener AL, James DE, Duh EJ &Watt MJ 2009 Pigment epithelium-derived factor contributes to insulin resistance in obesity. Cell Metabolism 10 40-47. (doi:10.1016/j.cmet.2009.06.001)
20. Davy KP & Orr JS 2009 Sympathetic nervous system behavior in human obesity. Neuroscience and Biobehavioral Reviews 33 116-124. (doi:10.1016/j. neubiorev.2008.05.024)
21. Delgado-Aros S & Camilleri M 2005 Visceral hypersensitivity. Journal of Clinical Gastroenterology 39 S194-S203 discussion S210. (doi:10.1097/01.mcg. 0000156114.22598.1b)
22. Dridi S & Taouis M 2009 Adiponectin and energy homeostasis: consensus and controversy. Journal of Nutritional Biochemistry 20 831-839. (doi:10.1016/j.jnutbio.2009.06.003)
23. Fasshauer M, Klein J, Neumann S, Eszlinger M & Paschke R 2001 Adiponectin gene expression is inhibited by beta-adrenergic stimulation via protein kinase A in 3T3-L1 adipocytes. FEBS Letters 507 142-146. (doi:10.1016/S0014-5793(01)02960-X) (Pubitemid 33001531)
24. Franklin BH, Whaley MH & Howley ET, eds 2000 ACSM's Guidelines For Exercise Testing and Prescription, ch. 4, pp 76-77. Philadelphia: Lippincott Williams and Wilkins.
25. Furlan R, Ardizzone S, Palazzolo L, Rimoldi A, Perego F, Barbic F, Bevilacqua M, Vago L, Bianchi Porro G & Malliani A 2006 Sympathetic overactivity in active ulcerative colitis: effects of clonidine. American Journal of Physiology. Regulatory, Integrative and Comparative Physiology 290 R224-R232. (doi:10.1152/ajpregu.00442.2005)
26. Grassi G, Seravalle G, Calhoun DA & Mancia G 1994 Physical training and baroreceptor control of sympathetic nerve activity in humans. Hypertension 23 294-301. (Pubitemid 24076710)
27. Grassi G, Seravalle G, Cattaneo BM, Bolla GB, Lanfranchi A, Colombo M, Giannattasio C, Brunani A, Cavagnini F & Mancia G 1995 Sympathetic activation in obese normotensive subjects. Hypertension 25 560-563.
28. Hoeks J, van Baak MA, Hesselink MK, Hul GB, Vidal H, Saris WH & Schrauwen P 2003 Effect of beta1- and beta2-adrenergic stimulation on energy expenditure, substrate oxidation, and UCP3 expression in humans. American Journal of Physiology. Endocrinology and Metabolism 285 E775-E782. (doi:10.1152/ajpendo.00175.2003)
29. Ishibashi J & Seale P 2010 Medicine. Beige can be slimming. Science 328 1113-1114. (doi:10.1126/science.1190816)
30. Jenkins AJ, Zhang SX, Rowley KG, Karschimkus CS, Nelson CL, Chung JS, O'Neal DN, Januszewski AS, Croft KD, Mori TA et al. 2007 Increased serum pigment epithelium-derived factor is associated with microvascular complications, vascular stiffness and inflammation in type 1 diabetes. Diabetic Medicine 24 1345-1351. (doi:10.1111/j.1464-5491.2007.02281.x)
31. Jocken JW, Blaak EE, van der Kallen CJ, van Baak MA & Saris WH 2008 Blunted beta-adrenoceptor-mediated fat oxidation in overweight subjects: a role for the hormone-sensitive lipase gene. Metabolism 57 326-332. (doi:10.1016/j.metabol.2007.10.006)
32. Jones PP, Davy KP & Seals DR 1997 Relations of total and abdominal adiposity to muscle sympathetic nerve activity in healthy older males. International Journal of Obesity and Related Metabolic Disorders 21 1053-1057. (doi:10.1038/sj.ijo.0800515)
33. Jones PP, Van Pelt RE, Johnson DG & Seals DR 2004 Role of sympathetic neural activation in age- and habitual exercise-related differences in the thermic effect of food. Journal of Clinical Endocrinology and Metabolism 89 5138-5144. (doi:10.1210/jc.2004-0101)
34. Klaus JR, Hurwitz BE, Llabre MM, Skyler JS, Goldberg RB, Marks JB, Bilsker MS & Schneiderman N 2009 Central obesity and insulin resistance in the cardiometabolic syndrome: pathways to preclinical cardiovascular structure and function. Journal of the Cardiometabolic Syndrome 4 63-71. (doi:10.1111/j.1559-4572.2008.00038.x)
35. Krukemyer JJ, Boudoulas H, Binkley PF & Lima JJ 1989 Biphasic pattern of hypersensitivity following acute propranolol withdrawal in normal subjects. Life Sciences 45 1547-1551. (doi:10.1016/0024-3205(89)90420-7) (Pubitemid 19264505)
36. Lam JC, Xu A, Tam S, Khong PI, Yao TJ, Lam DC, Lai AY, Lam B, Lam KS & Mary SM 2008 Hypoadiponectinemia is related to sympathetic activation and severity of obstructive sleep apnea. Sleep 31 1721-1727.
37. Lamont LS, Romito RA, Finkelhor RS & Kalhan SC 1997 Beta 1-adrenoreceptors regulate resting metabolic rate. Medicine and Science in Sports and Exercise 29 769-774. (Pubitemid 27290736)
38. Lashbrook BL & Steinle JJ 2005 Beta-adrenergic receptor regulation of pigment epithelial-derived factor expression in rat retina. Autonomic Neuroscience 121 33-39. (doi:10.1016/j.autneu.2005.05.006)
39. Laurent S & Safar M 1992 Rilmenidine: a novel approach to first-line treatment of hypertension. American Journal of Hypertension 5 99S-105S.
40. Leibowitz SF, Shor-Posner G, Brennan G & Alexander JT 1993 Meal pattern analysis of macronutrient intake after PVN norepinephrine and peripheral clonidine administration. Obesity Research 1 29-39.
41. Liggett SB 2001 Beta-adrenergic receptors in the failing heart: the good, the bad, and the unknown. Journal of Clinical Investigation 107 947-948. (doi:10.1172/JCI12774)
42. Lohse MJ, Engelhardt S, Danner S & Bohm M 1996 Mechanisms of beta-adrenergic receptor desensitization: from molecular biology to heart failure. Basic Research in Cardiology 91 29-34. (doi:10.1007/BF00795359) (Pubitemid 26397773)
43. Madden KM, Levy WC & Stratton JR 2006 Normal aging impairs upregulation of the beta-adrenergic but not the alpha-adrenergic response: aging and adrenergic upregulation. Journal of Cardiovascular Pharmacology 48 153-159. (doi:10.1097/01.fjc.0000246405.89380.48)
44. Mak S & Newton GE 2001 Vitamin C augments the inotropic response to dobutamine in humans with normal left ventricular function. Circulation 103 826-830. (Pubitemid 32163880)
45. Mak S & Newton GE 2004 Redox modulation of the inotropic response to dobutamine is impaired in patients with heart failure. American Journal of Physiology. Heart and Circulatory Physiology 286 H789-H795. (doi:10.1152/ ajpheart.00633.2003) (Pubitemid 38140363)
46. Mitchell A, Buhrmann S, Opazo Saez A, Rushentsova U, Schafers RF, Philipp T & Nurnberger J 2005 Clonidine lowers blood pressure by reducing vascular resistance and cardiac output in young, healthy males. Cardiovascular Drugs and Therapy 19 49-55. (doi:10.1007/s10557-005-6890-6)
47. Monroe MB, Van Pelt RE, Schiller BC, Seals DR & Jones PP 2000 Relation of leptin and insulin to adiposity-associated elevations in sympathetic activity with age in humans. International Journal of Obesity 24 1183-1187. (doi:10.1038/sj.ijo.0801364)
48. Monroe MB, Seals DR, Shapiro LF, Bell C, Johnson D & Jones PP 2001 Direct evidence for tonic sympathetic support of resting metabolic rate in healthy adult humans. American Journal of Physiology. Endocrinology and Metabolism 280 E740-E744. (Pubitemid 32466841)
49. Morrison P, Corcoran C & Vivet P 1990 Rilmenidine et vigilance. Journal of the American Medical Association (special issue, July) 27-28.
50. Muzi M, Goff DR, Kampine JP, Roerig DL & Ebert TJ 1992 Clonidine reduces sympathetic activity but maintains baroreflex responses in normotensive humans. Anesthesiology 77 864-871. (doi:10.1097/00000542-199211000-00005)
51. Nattel S, Rangno RE & Van Loon G 1979 Mechanism of propranolol withdrawal phenomena. Circulation 59 1158-1164.
52. Newsom SA, Paxton RJ, Rynn GM & Bell C 2008 Influence of ascorbic acid on the thermic effect of feeding in overweight and obese adult humans. Obesity 16 1749-1754. (doi:10.1038/oby.2008.304)
53. Ng AV, Callister R, Johnson DG & Seals DR 1994 Sympathetic neural reactivity to stress does not increase with age in healthy humans. American Journal of Physiology 267 H344-H353. (Pubitemid 2123452)
54. Nowak L, Adamczak M & Wiecek A 2005 Blockade of sympathetic nervous system activity by rilmenidine increases plasma adiponectin concentration in patients with essential hypertension. American Journal of Hypertension 18 1470-1475. (doi:10.1016/j.amjhyper.2005.05.026) (Pubitemid 41566678)
55. Prisant LM 2002 Transdermal clonidine skin reactions. Journal of Clinical Hypertension 4 136-138. (doi:10.1111/j.1524-6175.2001.00954.x)
56. Richards JC, Johnson TK, Kuzma JN, Lonac MC, Schweder MM, Voyles WF & Bell C 2010 Short-term sprint interval training increases insulin sensitivity in healthy adults but does not affect the thermogenic response to beta-adrenergic stimulation. Journal of Physiology (In Press). (doi:10.1113/jphysiol.2010.189886)
57. Rieg TS & Aravich PF 1994 Systemic clonidine increases feeding and wheel running but does not affect rate of weight loss in rats subjected to activity-based anorexia. Pharmacology, Biochemistry, and Behavior 47 215-218. (doi:10.1016/0091-3057(94)90002-7)
58. Ross EA, Pittman TB & Koo LC 2002 Strategy for the treatment of noncompliant hypertensive hemodialysis patients. International Journal of Artificial Organs 25 1061-1065. (Pubitemid 36040551)
59. Roveda F, Middlekauff HR, Rondon MU, Reis SF, Souza M, Nastari L, Barretto AC, Krieger EM & Negrao CE 2003 The effects of exercise training on sympathetic neural activation in advanced heart failure: a randomized controlled trial. Journal of the American College of Cardiology 42 854-860. (doi:10.1016/S0735-1097(03)00831-3)
60. Rychli K, Niessner A, Hohensinner PJ, Mahdy Ali K, Kaun C, Neuhold S, Zorn G, Richter B, Hulsmann M, Berger R et al. 2010 Prognostic value of pigment epithelium-derived factor in advanced heart failure patients. Chest (In Press). (doi:10.1378/chest.09-2739)
61. Scheidegger K, O'Connell M, Robbins DC & Danforth E Jr 1984 Effects of chronic beta-receptor stimulation on sympathetic nervous system activity, energy expenditure, and thyroid hormones. Journal of Clinical Endocrinology and Metabolism 58 895-903. (doi:10.1210/jcem-58-5-895) (Pubitemid 14102115)
62. Schiffelers SL, Saris WH, Boomsma F & van Baak MA 2001 Beta(1)- and beta(2)-Adrenoceptor-mediated thermogenesis and lipid utilization in obese and lean men. Journal of Clinical Endocrinology and Metabolism 86 2191-2199. (doi:10.1210/jc.86.5.2191) (Pubitemid 32472939)
63. Schwartz RS, Jaeger LF & Veith RC 1990a The thermic effect of feeding in older men: the importance of the sympathetic nervous system. Metabolism 39 733-737. (doi:10.1016/0026-0495(90)90109-P)
64. Schwartz RS, Jaeger LF, Veith RC & Lakshminarayan S 1990b The effect of diet or exercise on plasma norepinephrine kinetics in moderately obese young men. International Journal of Obesity 14 1-11. (Pubitemid 20123522)
65. Sharma AM, Pischon T, Hardt S, Kunz I & Luft FC 2001 Hypothesis: beta-adrenergic receptor blockers and weight gain: a systematic analysis. Hypertension 37 250-254. (Pubitemid 32199083)
66. Sica DA & Grubbs R 2005 Transdermal clonidine: therapeutic considerations. Journal of Clinical Hypertension 7 558-562. (doi:10.1111/j.1524- 6175.2005.04133.x)
67. Spraul M, Ravussin E, Fontvieille AM, Rising R, Larson DE & Anderson EA 1993 Reduced sympathetic nervous activity. A potential mechanism predisposing to body weight gain. Journal of Clinical Investigation 92 1730-1735. (doi:10.1172/JCI116760) (Pubitemid 23304536)
68. Steinle JJ, Cappocia FC Jr & Jiang Y 2008 Beta-adrenergic receptor regulation of growth factor protein levels in human choroidal endothelial cells. Growth Factors 26 325-330. (doi:10.1080/08977190802442070) (Pubitemid 352781845)
69. Stob NR, Bell C, van Baak MA & Seals DR 2007a Thermic effect of food and beta-adrenergic thermogenic responsiveness in habitually exercising and sedentary healthy adult humans. Journal of Applied Physiology 103 616-622. (doi:10.1152/japplphysiol.01434.2006) (Pubitemid 47204981)
70. Stob NR, Seals DR, Jorgen J, van Baak MA, Steig AJ, Lindstrom RC, Bikman BT & Bell C 2007b Increased thermogenic responsiveness to intravenous beta-adrenergic stimulation in habitually exercising humans is not related to skeletal muscle beta2-adrenergic receptor density. Experimental Physiology 92 823-830. (doi:10.1113/expphysiol.2007.038174)
71. Tanaka H, Monahan KD & Seals DR 2001 Age-predicted maximal heart rate revisited. Journal of the American College of Cardiology 37 153-156. (doi:10.1016/S0735-1097(00)01054-8) (Pubitemid 32051731)
72. Tappy L, Randin JP, Felber JP, Chiolero R, Simonson DC, Jequier E & DeFronzo RA 1986 Comparison of thermogenic effect of fructose and glucose in normal humans. American Journal of Physiology 250 E718-E724.
73. Vegiopoulos A, Muller-Decker K, Strzoda D, Schmitt I, Chichelnitskiy E, Ostertag A, Berriel Diaz M, Rozman J, Hrabe de Angelis M, Nusing RM et al. 2010 Cyclooxygenase-2 controls energy homeostasis in mice by de novo recruitment of brown adipocytes. Science 328 1158-1161. (doi:10.1126/science.1186034)
74. Wallin BG & Fagius J 1988 Peripheral sympathetic neural activity in conscious humans. Annual Reviews of Physiology 50 565-576. (doi:10.1146/annurev. ph.50.030188.003025) (Pubitemid 18088122)
75. Weir J 1949 New methods for calculating metabolic rate with special reference to protein metabolism. Journal of Physiology 109 1-9.
76. Welle S, Schwartz RG & Statt M 1991 Reduced metabolic rate during beta-adrenergic blockade in humans. Metabolism 40 619-622. (doi:10.1016/0026- 0495(91)90053-Y)
77. White M & Leenen FH 1994 Aging and cardiovascular responsiveness to beta-agonist in humans: role of changes in beta-receptor responses versus baroreflex activity. Clinical Pharmacology and Therapeutics 56 543-553. (Pubitemid 124006466)
78. White M, Roden R, Minobe W, Khan MF, Larrabee P, Wollmering M, Port JD, Anderson F, Campbell D & Feldman AM 1994 Age-related changes in beta-adrenergic neuroeffector systems in the human heart. Circulation 90 1225-1238.
79. Yamagishi S, Adachi H, Abe A, Yashiro T, Enomoto M, Furuki K, Hino A, Jinnouchi Y, Takenaka K, Matsui Tet al. 2006 Elevated serum levels of pigment epithelium-derived factor in the metabolic syndrome. Journal of Clinical Endocrinology and Metabolism 91 2447-2450. (doi:10.1210/jc.2005-2654)
80. Yamauchi T, Kamon J, Waki H, Terauchi Y, Kubota N, Hara K, Mori Y, Ide T, Murakami K, Tsuboyama-Kasaoka N et al. 2001 The fat-derived hormone adiponectin reverses insulin resistance associated with both lipoatrophy and obesity. Nature Medicine 7 941-946. (doi:10.1038/90984)
81. Zawilska JB, Zalewska-Kaszubska J, Marczak G, Gorska D & Woldan-Tambor A 2000 Characterization of beta-adrenergic receptors in duck cerebral cortex. Acta Neurobiologiae Experimentalis 60 301-307. (Pubitemid 30659906)
82. Zhang SX, Wang JJ, Dashti A, Wilson K, Zou MH, Szweda L, Ma JX & Lyons TJ 2008 Pigment epithelium-derived factor mitigates inflammation and oxidative stress in retinal pericytes exposed to oxidized low-density lipoprotein. Journal of Molecular Endocrinology 41 135-143. (doi:10.1677/JME-08- 0011)
83. Zoukos Y, Thomaides T, Pavitt DV, Cuzner ML & Mathias CJ 1993 Beta-adrenoceptor expression on circulating mononuclear cells of idiopathic Parkinson's disease and autonomic failure patients before and after reduction of central sympathetic outflow by clonidine. Neurology 43 1181-1187. (Pubitemid 23177720)
84. Zoukos Y, Thomaides T, Chaudhuri KR, Pavitt DV, Cuzner ML & Mathias CJ 1994 Expression of beta-adrenoceptors on circulating mononuclear cells in hypertensives and normotensives before and after reduction of central sympathetic outflow by clonidine. Blood Pressure 3 172-177. (doi:10.3109/ 08037059409102248) (Pubitemid 24169148)