title: Dehydroepiandrosterone (DHEA) prevents and reverses chronic hypoxic pulmonary hypertension.
abstract: Pulmonary artery (PA) hypertension was studied in a chronic hypoxic-pulmonary hypertension model (7-21 days) in the rat. Increase in PA pressure (measured by catheterism), cardiac right ventricle hypertrophy (determined by echocardiography), and PA remodeling (evaluated by histology) were almost entirely prevented after oral dehydroepiandrosterone (DHEA) administration (30 mg/kg every alternate day). Furthermore, in hypertensive rats, oral administration, or intravascular injection (into the jugular vein) of DHEA rapidly decreased PA hypertension. In PA smooth muscle cells, DHEA reduced the level of intracellular calcium (measured by microspectrofluorimetry). The effect of DHEA appears to involve a large conductance Ca2+-activated potassium channel (BKCa)-dependent stimulatory mechanism, at both function and expression levels (isometric contraction and Western blot), via a redox-dependent pathway. Voltage-gated potassium (Kv) channels also may be involved because the antagonist 4-amino-pyridine blocked part of the DHEA effect. The possible pathophysiological and therapeutic significance of the results is discussed.
authors.affiliation: Institut National de la Santé et de la Recherche Médicale, EMI 0356, Physiologie Cellulaire Respiratoire, Université de Bordeaux II, 146, Rue Léo Saignat, 33076 Bordeaux Cedex, France.
authors.forename: Sébastien
authors.initials: S
authors.lastname: Bonnet
authors.forename: Eric
authors.initials: E
authors.lastname: Dumas-de-La-Roque
authors.forename: Hugues
authors.initials: H
authors.lastname: Bégueret
authors.forename: Roger
authors.initials: R
authors.lastname: Marthan
authors.forename: Michael
authors.initials: M
authors.lastname: Fayon
authors.forename: Pierre
authors.initials: P
authors.lastname: Dos Santos
authors.forename: Jean-Pierre
authors.initials: JP
authors.lastname: Savineau
authors.forename: Etienne-Emile
authors.initials: EE
authors.lastname: Baulieu
mesh_terms: D000276:Adjuvants, Immunologic / Q000494:pharmacology; D000284:Administration, Oral; D000818:Animals; D015153:Blotting, Western; D002118:Calcium / Q000378:metabolism; D015220:Calcium Channels / Q000378:metabolism; D003687:Dehydroepiandrosterone / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D004452:Echocardiography; D006439:Hemodynamics; D006976:Hypertension, Pulmonary / Q000188:drug therapy*; D000860:Hypoxia; D008168:Lung / Q000378:metabolism; D008297:Male; D009200:Myocardial Contraction; D009206:Myocardium / Q000378:metabolism; D010084:Oxidation-Reduction; D015221:Potassium Channels / Q000378:metabolism; D011312:Pressure; D051381:Rats; D017208:Rats, Wistar
chemical_list: D000276:Adjuvants, Immunologic; D015220:Calcium Channels; D015221:Potassium Channels; D003687:Dehydroepiandrosterone; D002118:Calcium