Linked Life Data

11679412

Source:http://linkedlifedata.com/resource/pubmed/id/11679412

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
9
pubmed:dateCreated
2001-10-26
pubmed:abstractText
In vivo studies have suggested that norepinephrine (NE) directly contributes to normal vascular wall growth and worsening of hypertrophy, atherosclerosis, and restenosis. However, it is unknown whether these effects are secondary to hemodynamic changes caused by systemic NE or alpha-adrenoceptor (AR) antagonists. Herein, we determined if NE directly stimulates growth of medial smooth muscle cells (SMCs) and adventitial fibroblasts (AFBs) that we have shown express alpha1-ARs in similar abundance. The rat aorta was isolated before injury, 4 days after, or 12 days after balloon injury, and maintained under circumferential tension in organ culture for 48 hours with 1 micromol/L NE. Intima-media and adventitia were separated and DNA content, protein synthesis, and protein content measured. In uninjured aorta, NE increased DNA and protein content similarly in adventitia, and increased only protein content in intima-media, suggesting AFB proliferation and SMC hypertrophy. In vessels isolated 4 or 12 days after injury, NE increased all 3 endpoints in both layers by up to 20-fold greater than in uninjured vessels. These effects were dose-dependent and were unaffected by alpha2- or beta-AR blockade (except increased DNA content in adventitia that was also inhibited by alpha2-AR blockade). Intima-media growth was blocked by KMD3213 (alpha1A-AR antagonist) and adventitial growth by AH11110A (alpha1B-AR antagonist), whereas BMY7378 (alpha1D-AR antagonist) had no effect. NE decreased SMC marker proteins (eg, alpha-smooth muscle actin and desmin) and augmented the changes induced by injury. These data suggest that prolonged stimulation of alpha1A- and alpha1B-ARs induces growth of SMCs and AFBs, respectively, that is significantly augmented by injury.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Oct
pubmed:issn
1524-4571
pubmed:author
pubmed:issnType
Electronic
pubmed:day
26
pubmed:volume
89
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
815-22
pubmed:dateRevised
2010-11-18
pubmed:meshHeading
pubmed:year
2001
pubmed:articleTitle
Trophic effect of norepinephrine on arterial intima-media and adventitia is augmented by injury and mediated by different alpha1-adrenoceptor subtypes.
pubmed:affiliation
Department of Cell and Molecular Physiology, School of Medicine, University of North Carolina, Chapel Hill, NC 27599-7545, USA.
pubmed:publicationType
Journal Article, In Vitro, Research Support, U.S. Gov't, P.H.S.