Linked Life Data

9600652

Source:http://linkedlifedata.com/resource/pubmed/id/9600652

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
2-3
pubmed:dateCreated
1998-7-9
pubmed:abstractText
It has been suggested that reactive oxygen species may be involved in the regulation of vascular tone. However, the underlying mechanisms remain to be elucidated. The present studies were designed to investigate the contractile effects of hydrogen peroxide (H2O2), one of the reactive oxygen species, on isolated ring segments of rat aorta with and without endothelium. H2O2 induced an endothelium-independent contraction in isolated rat aorta ring segments in a concentration-dependent manner at concentrations from 5 x 10(-6) to 5 x 10(-3) M. H2O2-induced contractions of denuded rat aorta rings were stronger than those on intact rat aorta segments. The contractile effects of H2O2 were inhibited completely by 1200 u/ml catalase. The presence of 1.0 microM Fe2+ or 10 microM proadifen, a cytochrome P450 monooxygenase inhibitor, potentiated the contractile effect of H2O2 on isolated rat aorta segments. 1 mM deferoxamine (a Fe2+ chelator) or 100 microM dimethyl sulfoxide (a hydroxyl radical scavenger) significantly attenuated the vessel contractions induced by hydrogen peroxide plus Fe2+ or hydrogen peroxide itself. Removal of extracellular Ca2+ ([Ca2+]0), addition of 5 microM verapamil, administration of a protein kinase C inhibitor (staurosporine), treatment with an inhibitor of protein tyrosine phosphorylation (genistein) or employment of 5.0 microM indomethacin resulted in a significant attenuation of the contractile responses of the vessels to H2O2. Pharmacological antagonists (e.g. a muscarinic acetylcholine receptor antagonist (atropine), an antagonist of histamine H1 receptors (diphenhydramine), an antagonist of histamine H2 receptors (cimetidine), an alpha-adrenoceptor antagonist (phentolamine), a beta-adrenoceptor antagonist (propranolol) and an antagonist of serotonin receptor (methysergide)) did not inhibit or attenuate the contractions induced by H2O2. Exposure of primary aortic smooth muscle cells to H2O2 (5 x 10(-6) to 5 x 10(-3) M) produced significant rises of intracellular Ca2+ ([Ca2+]i) within 20 s. Employment of 1.0 microM Fe2+ markedly enhanced the increment in [Ca2+]i in the smooth muscle cells. 10 microM proadifen treatment failed to alter the hydrogen peroxide-induced increment in [Ca2+]i of the smooth muscle cells. However, the presence of 5 microM indomethacin significantly attenuated the rise in [Ca2+]i in smooth muscle cells. The present results suggest that H2O2 can induce contractions of rat aorta segments, at pathophysiological concentrations, which are Ca2+-dependent. Hydroxyl radicals (.OH), cyclooxygenase products, protein kinase C and products of protein tyrosine phosphorylation appear to play some role in hydrogen peroxide-induced contractions. Metabolites catalyzed by cytochrome P450-dependent enzymes (upon treatment with hydrogen peroxide) appear to exert a vasodilator effect on rat aorta segments. Lastly, some unidentified mediators, produced by a cytochrome P450 inhibitor (proadifen), during hydrogen peroxide treatment, appear to play some role in contraction of vascular smooth muscle of rat aorta segments in vitro.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Mar
pubmed:issn
0014-2999
pubmed:author
pubmed:issnType
Print
pubmed:day
5
pubmed:volume
344
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
169-81
pubmed:dateRevised
2007-11-14
pubmed:meshHeading
pubmed:year
1998
pubmed:articleTitle
Mechanisms of hydrogen peroxide-induced contraction of rat aorta.
pubmed:affiliation
Department of Physiology, Health Science Center at Brooklyn, State University of New York, 11203, USA.
pubmed:publicationType
Journal Article, Comparative Study, In Vitro, Research Support, U.S. Gov't, P.H.S.