Bluthochdruck und sympathisches Nervensystem – neue Entwicklungen in Forschung und Therapie

Zusammenfassung

Das sympathische Nervensystem ist wesentlich an der Kreislaufregulation beteiligt und bietet pharmakotherapeutische und nicht-pharmakologische Interventionsmöglichkeiten zur Behandlung der arteriellen Hypertonie. Aktuelle Forschungsergebnisse zur Organisation der Adrenorezeptoren in Multiproteinkomplexen haben unsere Kenntnisse zur Blutdruckregulation erweitert und können der pharmakologischen und genetischen Forschung auf dem Gebiet der Hypertensiologie neue Impulse verleihen. Neue Entwicklungen der biomedizinischen Technik ermöglichen nicht-pharmakologische sympathikolytische Interventionen, die insbesondere bei pharmakotherapieresistenten Hypertonieformen die Behandlungsmöglichkeiten erweitern.

Summary

The sympathetic nervous system importantly contributes to the control of the circulation and is an important therapeutic target to lower arterial pressure in hypertensive patients. Recent advances in the understanding of the organization of adrenergic receptors in multiprotein complexes have improved our understanding of arterial pressure control and may have impact on drug development and genetic research in the field of hypertension. New developments in biomedical technology allow for non-pharmacological interventions to reduce sympathetic activity and provide new options to treat hypertensive patients who are resistant to antihypertensive drug therapy.

Schlüsselwörter

arterielle Hypertonie - Antihypertonika - Sympathikusaktivierung

Keywords

arterial hypertension - antihypertensive drugs - sympathetic activation

Literatur

• 1 Augustyniak R A, Tuncel M, Zhang W, Toto R D, Victor R G. Sympathetic overactivity as a cause of hypertension in patients with chronic renal failure.  J Hypertens. 2002;  20 3-9
• 2 Bibutay A M, Lillehei C W. Surgical treatment of hypertension with reference to baropacing.  Am J Cardiol. 1966;  17 663-667
• 3 DiBona G F, Kopp U C. Neural control of renal function.  Physiol Rev. 1997;  77 75-197
• 4 Grisk O, Rettig R. Interactions between the sympathetic nervous system and the kidneys in arterial hypertension.  Cardiovasc Res. 2004;  61 238-246
• 5 Gu S, Cifelli C, Wang S, Heximer S P. RGS proteins: identifying new GAPs in the understanding of blood pressure regulation and cardiovascular function.  Clin Sci. 2009;  116 391-399
• 6 Hague C, Bernstein L S, Raminemi S, Chen R, Minneman K P, Hepler J R. Selective inhibition of α_1A-adrenergic receptor signaling by RGS2 association with the receptor third intracellular loop.  J Biol Chem. 2005;  280 27289-27295
• 7 Hausberg M, Kosch M, Harmelink P, Barenbrock M, Hohage H, Kisters K, Dietl K H, Rahn K H. Sympathetic nerve activity in end-stage renal disease.  Circulation. 2002;  106 1974-1979
• 8 Heximer S P, Knutsen R H, Sun X, Kaltenbronn K M, Rhee M -H, Peng N, Oliveira-dos-Santos A, Penninger J M, Muslin A J, Steinberg T H, Wyss J M, Mecham R P, Blumer K J. Hypertension and prolonged vasoconstrictor signaling in RGS2-deficient mice.  J Clin Invest. 2003;  111 445-452
• 9 Illing K A, Levy M, Sanchez L, Trachiotis G D, Shanley C, Irwin E, Pertile T, Kieval R, Cody R. An implantable carotid sinus stimulator for drug-resistant hypertension: surgical technique and short-term outcome from the multicenter phase II Rheos feasibility trial.  J Vasc Surg. 2006;  44 1213-1218
• 10 Kirstein S L, Insel P A. Autonomic nervous system pharmacogenomics: a progress report.  Pharmacol Rev. 2004;  56 31-52
• 11 Krum H, Schlaich M, Whitbourn R, Sobotka P A, Sadowski J, Bartus K, Kapelak B, Walton A, Sievert H, Thambar S, Abraham W T, Esler M. Catheter-based renal sympathetic denervation for resistant hypertension: a multicentre safety and proof-of-priciple cohort study.  Lancet. 2009;  373 1275-1281
• 12 Leitlinien zur Behandlung der arteriellen Hypertonie. Deutsche Hochdruckliga e. V. DHL® – Deutsche Hypertonie Gesellschaft, Heidelberg. 2008
• 13 Levy D, Ehret G B, Rice K, Verwoert G C, Launer L J, Dehghan A. et al . Genome-wide association study of blood pressure and hypertension.  Nat Genetics. 2009;  41 677-687
• 14 Lindholm L H, Carlberg B, Samuelsson O. Should β blockers remain the first choice in the treatment of primary hypertension? A meta-analysis.  Lancet. 2005;  366 1545-1553
• 15 Lohmeier T E, Irwin E D, Rossing M A, Serdar D J, Kieval R S. Prolonged activation of the baroreflex produces sustained hypotension.  Hypertension. 2004;  43 306-311
• 16 Lohmeier T E, Hidebrandt D A, Dwyer T M, Iliescu R, Irwin E D, Cates A W. Prolonged activation of the baroreflex deceases arterial pressure even during adrenergic blockade.  Hypertension. 2009;  53 833-838
• 17 Lyssand J S, DeFino M C, Tang X, Hertz A L, Feller D G, Wacker J L, Adams M, Hague C. Blood pressure is regulated by an α_1D-adrenergic receptor/dystrophin signalosome.  J Biol Chem. 2008;  283 18792-18800
• 18 Newton-Cheh C, Johnson T, Gateva V, Tobin M D, Bochud M, Coin L. et al . Genome-wide association study identifies eight loci associated with blood pressure.  Nat Genetics. 2009;  41 666-676
• 19 Scheffers I, Schmidli J, Kroon A A, Tordoir J, Mohaupt M, Allemann Y, Jordan J, Engeli S, Liebeskind U, Luft F C, Eckert S, Hansky B, Baal T, de Leeuw P W. Sustained blood pressure reduction by baroreflex hypertension therapy with a chronically implanted system: 2-year data from the Rheos Debut-HT study in patients with resistant hypertension.  J Hypertens. 2008;  26 (Suppl 1) S19
• 20 Suzuki F, Morishima S, Tanaka T, Muramatsu I. Snapin, a new regulator of receptor signaling, augments α_1A-adrenoceptor-operated calcium influx through TRPC6.  J Biol Chem. 2007;  282 29563-29573