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This Article Full Text Full Text (PDF) All Versions of this Article: 291/5/H2272    most recent 00404.2006v1 Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in ISI Web of Science Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via ISI Web of Science (1) Citing Articles via Google Scholar Google Scholar Articles by Faber, J. E. Articles by Zhang, H. Search for Related Content PubMed PubMed Citation Articles by Faber, J. E. Articles by Zhang, H.

Enhanced ₁-adrenergic trophic activity in pulmonary artery of hypoxic pulmonary hypertensive rats

Departments of ¹Cell and Molecular Physiology, School of Medicine and ²Biology, University of North Carolina, Chapel Hill, North Carolina; and ³Chest Research Foundation, Pune, India

Submitted 19 April 2006 ; accepted in final form 12 June 2006

Mechanisms that induce the excessive proliferation of vascular wall cells in hypoxic pulmonary hypertension (PH) are not fully understood. Alveolar hypoxia causes sympathoexcitation, and norepinephrine can stimulate ₁-adrenoceptor (₁-AR)-dependent hypertrophy/hyperplasia of smooth muscle cells and adventitial fibroblasts. Adrenergic trophic activity is augmented in systemic arteries by injury and altered shear stress, which are key pathogenic stimuli in hypoxic PH, and contributes to neointimal formation and flow-mediated hypertrophic remodeling. Here we examined whether norepinephrine stimulates growth of the pulmonary artery (PA) and whether this is augmented in PH. PA from normoxic and hypoxic rats [9 days of 0.1 fraction of inspired O₂ (FI_O2)] was studied in organ culture, where wall tension, PO₂, and PCO₂ were maintained at values present in normal and hypoxic PH rats. Norepinephrine treatment for 72 h increased DNA and protein content modestly in normoxic PA (+10%, P < 0.05). In hypoxic PA, these effects were augmented threefold (P < 0.05), and protein synthesis was increased 34-fold (P < 0.05). Inferior thoracic vena cava from normoxic or hypoxic rats was unaffected. Norepinephrine-induced growth in hypoxic PA was dose dependent, had efficacy greater than or equal to endothelin-1, required the presence of wall tension, and was inhibited by _1A-AR antagonist. In hypoxic pulmonary vasculature, _1A-AR was downregulated the least among ₁-AR subtypes. These data demonstrate that norepinephrine has trophic activity in the PA that is augmented by PH. If evident in vivo in the pulmonary vasculature, adrenergic-induced growth may contribute to the vascular hyperplasia that participates in hypoxic PH.

vascular smooth muscle; hypertrophy; catecholamines; adrenergic receptors; hypoxia

This article has been cited by other articles:

				J. E. Faber, C. L. Szymeczek, S. Cotecchia, S. A. Thomas, A. Tanoue, G. Tsujimoto, and H. Zhang {alpha}1-Adrenoceptor-dependent vascular hypertrophy and remodeling in murine hypoxic pulmonary hypertension Am J Physiol Heart Circ Physiol, May 1, 2007; 292(5): H2316 - H2323. [Abstract] [Full Text] [PDF]