Linked Life Data

16798826

Source:http://linkedlifedata.com/resource/pubmed/id/16798826

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
5
pubmed:dateCreated
2006-10-10
pubmed:abstractText
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 alpha(1)-adrenoceptor (alpha(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 O(2) (Fi(O(2)))] was studied in organ culture, where wall tension, Po(2), and Pco(2) 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 alpha(1A)-AR antagonist. In hypoxic pulmonary vasculature, alpha(1A)-AR was downregulated the least among alpha(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.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Nov
pubmed:issn
0363-6135
pubmed:author
pubmed:issnType
Print
pubmed:volume
291
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
H2272-81
pubmed:dateRevised
2010-11-18
pubmed:meshHeading
pubmed-meshheading:16798826-Adrenergic alpha-1 Receptor Agonists, pubmed-meshheading:16798826-Adrenergic alpha-1 Receptor Antagonists, pubmed-meshheading:16798826-Animals, pubmed-meshheading:16798826-Anoxia, pubmed-meshheading:16798826-DNA, pubmed-meshheading:16798826-Dose-Response Relationship, Drug, pubmed-meshheading:16798826-Endothelin-1, pubmed-meshheading:16798826-Fibroblasts, pubmed-meshheading:16798826-Hypertension, Pulmonary, pubmed-meshheading:16798826-Male, pubmed-meshheading:16798826-Muscle, Smooth, Vascular, pubmed-meshheading:16798826-Norepinephrine, pubmed-meshheading:16798826-Organ Culture Techniques, pubmed-meshheading:16798826-Proteins, pubmed-meshheading:16798826-Pulmonary Artery, pubmed-meshheading:16798826-Rats, pubmed-meshheading:16798826-Rats, Sprague-Dawley, pubmed-meshheading:16798826-Receptors, Adrenergic, alpha-1, pubmed-meshheading:16798826-Time Factors
pubmed:year
2006
pubmed:articleTitle
Enhanced alpha1-adrenergic trophic activity in pulmonary artery of hypoxic pulmonary hypertensive rats.
pubmed:affiliation
Dept. of Cell and Molecular Physiology, 6309 MBRB, Univ. of North Carolina, Chapel Hill, NC 27599-7545, USA. jefaber@med.unc.edu
pubmed:publicationType
Journal Article, Comparative Study, Research Support, N.I.H., Extramural