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Adipositas - Ursachen, Folgeerkrankungen, Therapie 2007; 01(02): 70-73
DOI: 10.1055/s-0037-1618560
Hypertonie bei Adipositas
Schattauer GmbH

Pathophysiologie der Adipositas-assoziierten Hypertonie

Pathophysiology of obesity-associated hypertension
U. Kintscher
1   Center for Cardiovascular Research (CCR), Institut für Pharmakologie, Charité – Universitätsmedizin Berlin
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Publication History

Publication Date:
21 December 2017 (online)

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Zusammenfassung

Die Pathophysiologie der Adipositas-assoziierten Hypertonie ist ein multifaktorielles Geschehen. Im Zentrum dieser Vorgänge steht ein erhöhtes Herzminutenvolumen (HMV) mit begleitendem Anstieg des peripheren vaskulären Widerstands. Die Zunahme des HMV ist Folge einer Vermehrung des intravasalen Volumens, hervorgerufen durch eine Stimulation der renalen Natriumretention. Diese Prozesse werden maßgeblich durch eine verstärkte Aktivität des sympathischen Nervensystems (SNS), die Aktivierung des Renin-Angiotensin-Aldosteron-Systems (RAAS) und strukturelle Nierenveränderungen verursacht. Wichtige Mediatoren der SNS-Aktivierung bei Adipositas sind Hyperinsulinämie, erhöhte Plasmaleptinspiegel und obstruktive Schlafapnoe. Die Aktivierung des RAAS ist wesentlich durch die verstärkte Aktivität eines lokalen RAAS in der zunehmenden Fettmasse verursacht. Zusätzlich rückt die Bedeutung des perivaskulären Fetts als vasoaktives Gewebe zunehmend in den Mittelpunkt der heutigen Untersuchungen. Eine Dysregulation der sekretorischen Funktion des perivaskulären Fetts könnte ein wichtiger pathophysiologischer Faktor bei der Entstehung der Adipositas-assoziierten Hypertonie sein. Eine pharmakologische Intervention zur Behandlung der Adipositas-assoziierten Hypertonie sollte sich an den genannten Prinzipien orientieren.

Summary

The pathophysiology of obesity-associated hypertension is a multifactorial process. An increased cardiac output has been identified as an important pathophysiological mediator accompanied by augmented peripheral vascular resistance. The enhanced cardiac output likely results from plasma volume expansion due to enhanced renal sodium retention. These processes are mainly mediated by activation of the sympathetic nervous system (SNS) and the renin-angiotensin-aldosterone-system (RAAS) during obesity as well as by structural kidney changes. Important stimulators of SNS-activity have been described in obesity including hyperinsulinemia, increased plasma leptin levels, and obstructive sleep apnea. Exaggerated RAAS activation might be attributed to an enhanced activity of a local RAAS in the incremental adipose tissue mass. In addition, perivascular fat is gaining increased attention as a vasoactive tissue. A dysregulated secretory function of perivascular fat might be an important pathophysiological initiator during the development of obesity-associated hypertension. A pharmacological treatment strategy for obesity-associated hypertension absolutely requires the integration of these pathophysiological principles.

Schlüsselwörter

Adipositas-assoziierte Hypertonie - sympathisches Nervensystem - Renin-Angiotensin-Aldosteron-System

Keywords

Obesity-associated hypertension - sympathetic nervous system - renin-angiotensin-aldosterone-system
 

  • Literatur

  • 1 Alvarez GE, Beske SD, Ballard TP, Davy KP. Sympathetic neural activation in visceral obesity. Circulation 2002; 106 (20) 2533-2536.
    CrossrefPubMedGoogle Scholar
  • 2 Davy KP, Hall JE. Obesity and hypertension: two epidemics or one?. Am J Physiol Regul Integr Comp Physiol 2004; 286 (05) R803-813.
    CrossrefPubMedGoogle Scholar
  • 3 Engeli S, Negrel R, Sharma AM. Physiology and pathophysiology of the adipose tissue renin-angiotensin system. Hypertension 2000; 35 (06) 1270-1277.
    CrossrefPubMedGoogle Scholar
  • 4 Engeli S, Bohnke J, Gorzelniak K, Janke J, Schling P, Bader M, Luft FC, Sharma AM. Weight loss and the renin-angiotensin-aldosterone system. Hypertension 2005; 45 (03) 356-362.
    CrossrefPubMedGoogle Scholar
  • 5 Esler M, Straznicky N, Eikelis N, Masuo K, Lambert G, Lambert E. Mechanisms of sympathetic activation in obesity-related hypertension. Hypertension 2006; 48 (05) 787-796.
    CrossrefPubMedGoogle Scholar
  • 6 Fox CS. et al. Abdominal visceral and subcutaneous adipose tissue compartments: association with metabolic risk factors in the Framingham Heart Study. Circulation 2007; 116 (01) 39-48.
    CrossrefPubMedGoogle Scholar
  • 7 Galvez B. et al. Perivascular adipose tissue and mesenteric vascular function in spontaneously hypertensive rats. Arterioscler Thromb Vasc Biol 2006; 26 (06) 1297-1302.
    CrossrefPubMedGoogle Scholar
  • 8 Garrison RJ, Kannel WB, Stokes 3rd J, Castelli WP. Incidence and precursors of hypertension in young adults: the Framingham Offspring Study. Prev Med 1987; 16 (02) 235-251.
    CrossrefPubMedGoogle Scholar
  • 9 Grossman E, Eshkol A, Rosenthal T. Diet and weight loss: their effect on norepinephrine renin and aldosterone levels. Int J Obes 1985; 09 (02) 107-114.
    PubMedGoogle Scholar
  • 10 Hall JE, Hildebrandt DA, Kuo J. Obesity hypertension: role of leptin and sympathetic nervous system. Am J Hypertens 2001; 14 (6 Pt 2): 103S-115S.
    CrossrefPubMedGoogle Scholar
  • 11 Haynes WG, Sivitz WI, Morgan DA, Walsh SA, Mark AL. Sympathetic and cardiorenal actions of leptin. Hypertension 1997; 30 (3 Pt 2): 619-623.
    CrossrefPubMedGoogle Scholar
  • 12 Iacobellis G, Corradi D, Sharma AM. Epicardial adipose tissue: anatomic, biomolecular and clinical relationships with the heart. Nat Clin Pract Cardiovasc Med 2005; 02 (10) 536-543.
    CrossrefPubMedGoogle Scholar
  • 13 Landsberg L, Young JB. Fasting, feeding and regulation of the sympathetic nervous system. N Engl J Med 1978; 298 (23) 1295-1301.
    CrossrefPubMedGoogle Scholar
  • 14 Lohn M, Dubrovska G, Lauterbach B, Luft FC, Gollasch M, Sharma AM. Periadventitial fat releases a vascular relaxing factor. Faseb J 2002; 16 (09) 1057-1063.
    CrossrefPubMedGoogle Scholar
  • 15 Mackintosh RM, Hirsch J. The effects of leptin administration in non-obese human subjects. Obes Res 2001; 09 (08) 462-469.
    CrossrefPubMedGoogle Scholar
  • 16 Massiera F. et al. Adipose angiotensinogen is involved in adipose tissue growth and blood pressure regulation. Faseb J 2001; 15 (14) 2727-2729.
    CrossrefPubMedGoogle Scholar
  • 17 Masuo K, Mikami H, Ogihara T, Tuck ML. Sympathetic nerve hyperactivity precedes hyperinsulinemia and blood pressure elevation in a young, nonobese Japanese population. Am J Hypertens 1997; 10 (01) 77-83.
    CrossrefPubMedGoogle Scholar
  • 18 Messerli FH, Christie B, DeCarvalho JG, Aristimuno GG, Suarez DH, Dreslinski GR, Frohlich ED. Obesity and essential hypertension. Hemodynamics, intravascular volume, sodium excretion, and plasma renin activity. Arch Intern Med 1981; 141 (01) 81-85.
    CrossrefPubMedGoogle Scholar
  • 19 Must A, Spadano J, Coakley EH, Field AE, Colditz G, Dietz WH. The disease burden associated with overweight and obesity. JAMA 1999; 282 (16) 1523-1529.
    CrossrefPubMedGoogle Scholar
  • 20 Narkiewicz K, van de Borne PJ, Cooley RL, Dyken ME, Somers VK. Sympathetic activity in obese subjects with and without obstructive sleep apnea. Circulation 1998; 98 (08) 772-776.
    CrossrefPubMedGoogle Scholar
  • 21 Scaglione R, Ganguzza A, Corrao S, Parrinello G, Merlino G, Dichiara MA, Arnone S, D’Aubert MD, Licata G. Central obesity and hypertension: pathophysiologic role of renal haemodynamics and function. Int J Obes Relat Metab Disord 1995; 19 (06) 403-409.
    PubMedGoogle Scholar
  • 22 Scherrer U, Randin D, Tappy L, Vollenweider P, Jequier E, Nicod P. Body fat and sympathetic nerve activity in healthy subjects. Circulation 1994; 89 (06) 2634-2640.
    CrossrefPubMedGoogle Scholar
  • 23 Scholze J, Grimm E, Herrmann D, Unger T, Kintscher U. Optimal treatment of obesity-related hypertension: the Hypertension-Obesity-Sibutramine (HOS) study. Circulation 2007; 115 (15) 1991-1998.
    CrossrefPubMedGoogle Scholar
  • 24 Sharma AM, Pischon T, Engeli S, Scholze J. Choice of drug treatment for obesity-related hypertension: where is the evidence?. J Hypertens 2001; 19 (04) 667-674.
    CrossrefPubMedGoogle Scholar
  • 25 Soltis EE, Cassis LA. Influence of perivascular adipose tissue on rat aortic smooth muscle responsiveness. Clin Exp Hypertens 1991; 13 (02) 277-296.
    PubMedGoogle Scholar
  • 26 Somers VK, Dyken ME, Clary MP, Abboud FM. Sympathetic neural mechanisms in obstructive sleep apnea. J Clin Invest 1995; 96 (04) 1897-1904.
    CrossrefPubMedGoogle Scholar
  • 27 Stelfox HT, Ahmed SB, Ribeiro RA, Gettings EM, Pomerantsev E, Schmidt U. Hemodynamic monitoring in obese patients: the impact of body mass index on cardiac output and stroke volume. Crit Care Med 2006; 34 (04) 1243-1246.
    CrossrefPubMedGoogle Scholar
  • 28 Tuck ML, Sowers J, Dornfeld L, Kledzik G, Maxwell M. The effect of weight reduction on blood pressure, plasma renin activity, and plasma aldosterone levels in obese patients. N Engl J Med 1981; 304 (16) 930-933.
    CrossrefPubMedGoogle Scholar
  • 29 Umemura S, Nyui N, Tamura K, Hibi K, Yamaguchi S, Nakamaru M, Ishigami T, Yabana M, Kihara M, Inoue S, Ishii M. Plasma angiotensinogen concentrations in obese patients. Am J Hypertens 1997; 10 (06) 629-633.
    CrossrefPubMedGoogle Scholar
  • 30 Verlohren S, Dubrovska G, Tsang SY, Essin K, Luft FC, Huang Y, Gollasch M. Visceral periadventitial adipose tissue regulates arterial tone of mesenteric arteries. Hypertension 2004; 44 (03) 271-276.
    CrossrefPubMedGoogle Scholar
  • 31 Vollenweider P, Tappy L, Randin D, Schneiter P, Jequier E, Nicod P, Scherrer U. Differential effects of hyperinsulinemia and carbohydrate metabolism on sympathetic nerve activity and muscle blood flow in humans. J Clin Invest 1993; 92 (01) 147-154.
    CrossrefPubMedGoogle Scholar
  • 32 Yudkin JS, Eringa E, Stehouwer CD. “Vasocrine” signalling from perivascular fat: a mechanism linking insulin resistance to vascular disease. Lancet 2005; 365 (9473): 1817-1820.
    CrossrefPubMedGoogle Scholar