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Die Wirkungen von Dehydroepiandrosteron auf die glatte Muskulatur von Aorta und Trachea der Ratte

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  • Dehydroepiandrosterone (3-hydroxy-5-androsten-17-one) and its sulfate ester are major secretory products of the adrenal cortex. The exact physiological role of DHEA is unknown. Dehydroepiandrosterone opens calcium activated potassium channels (KCa), and diminishes hypoxia induced pulmonary vascular resistance in ferret lungs presumably by relaxing arterial smooth muscle. However, there are few data about direct effects of DHEA on smooth muscle contractility and particularly bronchial smooth muscle. The aim of the study was to determine functional significance of potential potassium channel activator DHEA as smooth muscle relaxant in rat aorta and trachea. Working hypothesis was that DHEA is potent broncho- and vasodilatatorand and that its relaxing effects could be linked to its potassium channel activating property. In preliminary experiments we already examined the in vitro contractility of rat aortic and tracheal rings. The potassium channel blocking agents tetraethylamonium, glibenclamide, 4-aminopyridine, and charybdotoxin could neither reverse nor prevent relaxation induced by DHEA. Further examination of the DHEA effects involved different experimental protocols. We examined the effects of DHEA on smooth muscle rings of rat trachea or aorta in vitro, pre-contracted with carbachol or phenylephrine. The observed effects were investigated in preparations with or without epithelium or endothelium; also we examined the effect of DHEA on 40 or 80 mM potassium chloride (KCI) pre-contracted preparations. Reversal or prevention of DHEA relaxant effect was attemted by blocking cyclic nucleotides synthesis with 1H-[1,2,4]oxadiazolo[4,3a]quinoxalin-1-one (ODQ) or 9-(tetrahydro-2-furanyl)-9H-purin-6-amine (SQ 22536), or by preventing calcium removal with thapsigargin. We found that DHEA induces relaxation of rat tracheal and arterial smooth muscle and that the potassium channels are at least partially involved. For future investigations it would be important to examine preventive effects of DHEA on allergic bronchoconstriction in animals or in human bronchus. Potentially DHEA could be considered as relevant therapeutics for well determined conditions. In respect to the mechanisms of action of DHEA further effects on the level of the cell membrane (ion channels, potential receptors) and the intracellular messenger system (IP3, G-proteins, proteinkinase C, myosin light chain kinase, protein phosphorylation) could be examined.

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Author: Juliane Maskow
Title Additional (English):Effects of Dehydroepiandrosterone on smooth muscle of rat aorta and trachea
Advisor:Prof. Dr. Michael Wendt
Document Type:Doctoral Thesis
Date of Publication (online):2006/07/04
Granting Institution:Ernst-Moritz-Arndt-Universität, Medizinische Fakultät (bis 2010)
Date of final exam:2005/10/04
Release Date:2006/07/04
GND Keyword:Dehydroepiandrosteron, Aorta, Luftröhre, Ratte
Faculties:Universitätsmedizin / Klinik für Anästhesiologie und Intensivmedizin
DDC class:600 Technik, Medizin, angewandte Wissenschaften / 610 Medizin und Gesundheit