Alpha1-adrenoceptor-dependent vascular hypertrophy and remodeling in murine hypoxic pulmonary hypertension.

Détails

ID Serval
serval:BIB_2DCF676DA1DE
Type
Article: article d'un périodique ou d'un magazine.
Collection
Publications
Titre
Alpha1-adrenoceptor-dependent vascular hypertrophy and remodeling in murine hypoxic pulmonary hypertension.
Périodique
American Journal of Physiology. Heart and Circulatory Physiology
Auteur(s)
Faber J.E., Szymeczek C.L., Cotecchia S., Thomas S.A., Tanoue A., Tsujimoto G., Zhang H.
ISSN
0363-6135 (Print)
ISSN-L
0363-6135
Statut éditorial
Publié
Date de publication
2007
Peer-reviewed
Oui
Volume
292
Numéro
5
Pages
H2316-H2323
Langue
anglais
Résumé
Excessive proliferation of vascular wall cells underlies the development of elevated vascular resistance in hypoxic pulmonary hypertension (PH), but the responsible mechanisms remain unclear. Growth-promoting effects of catecholamines may contribute. Hypoxemia causes sympathoexcitation, and prolonged stimulation of alpha(1)-adrenoceptors (alpha(1)-ARs) induces hypertrophy and hyperplasia of arterial smooth muscle cells and adventitial fibroblasts. Catecholamine trophic actions in arteries are enhanced when other conditions favoring growth or remodeling are present, e.g., injury or altered shear stress, in isolated pulmonary arteries from rats with hypoxic PH. The present study examined the hypothesis that catecholamines contribute to pulmonary vascular remodeling in vivo in hypoxic PH. Mice genetically deficient in norepinephrine and epinephrine production [dopamine beta-hydroxylase(-/-) (DBH(-/-))] or alpha(1)-ARs were examined for alterations in PH, cardiac hypertrophy, and vascular remodeling after 21 days exposure to normobaric 0.1 inspired oxygen fraction (Fi(O(2))). A decrease in the lumen area and an increase in the wall thickness of arteries were strongly inhibited in knockout mice (order of extent of inhibition: DBH(-/-) = alpha(1D)-AR(-/-) > alpha(1B)-AR(-/-)). Distal muscularization of small arterioles was also reduced (DBH(-/-) > alpha(1D)-AR(-/-) > alpha(1B)-AR(-/-) mice). Despite these reductions, increases in right ventricular pressure and hypertrophy were not attenuated in DBH(-/-) and alpha(1B)-AR(-/-) mice. However, hematocrit increased more in these mice, possibly as a consequence of impaired cardiovascular activation that occurs during reduction of Fi(O(2)). In contrast, in alpha(1D)-AR(-/-) mice, where hematocrit increased the same as in wild-type mice, right ventricular pressure was reduced. These data suggest that catecholamine stimulation of alpha(1B)- and alpha(1D)-ARs contributes significantly to vascular remodeling in hypoxic PH.
Mots-clé
Animals, Anoxia/complications, Anoxia/metabolism, Hypertension, Pulmonary/etiology, Hypertension, Pulmonary/metabolism, Hypertrophy/metabolism, Hypertrophy/pathology, Male, Mice, Mice, Inbred C57BL, Norepinephrine/metabolism, Pulmonary Artery/metabolism, Pulmonary Artery/pathology, Receptors, Adrenergic, alpha-1
Pubmed
Web of science
Création de la notice
24/01/2008 11:05
Dernière modification de la notice
20/08/2019 13:12
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