Source:http://linkedlifedata.com/resource/pubmed/id/15464071
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rdf:type | |
lifeskim:mentions | |
pubmed:issue |
1-3
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pubmed:dateCreated |
2004-10-6
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pubmed:abstractText |
We aimed to investigate the role of K(+) channels and nitric oxide (NO) on the relaxant effects of arachidonic acid in the human intralobar pulmonary arteries. Arachidonic acid produced a concentration-dependent relaxation (E(max)=93+/-3% of maximal relaxation induced by papaverine 0.1 mM;-log EC(30)=7.03+/-0.09) that was antagonized by the cyclooxygenase inhibitor indomethacin (1 microM), by the combination of cyclooxygenase blockade and cytochrome P450 (CYP) blockade with 17-octadecynoic acid (17-ODYA, 10 microM), by the combination of cyclooxygenase inhibition and NO synthase (NOS) inhibition with N(omega)-nitro-l-arginine (l-NOARG, 100 microM), by the simultaneous inhibition of CYP and NOS and by the simultaneous blockade of cyclooxygenase, CYP and NOS. Arachidonic acid-induced relaxation was significantly inhibited by glibenclamide (1 microM, ATP-dependent K(+) channel (K(ATP)) blocker), apamin and charybdotoxin (0.3 microM small (SK(Ca)) and 0.1 microM big (BK(Ca)) conductance Ca(2+)-sensitive K(+) channel blocker, respectively), and 4-aminopyridine (1 mM, voltage-dependent K(+) channel (K(V)) blocker). Indomethacin and ketoconazole suppressed the antagonistic effects of glibenclamide and apamin and 17-ODYA those of all the K(+) channel blockers tested. l-NOARG suppressed only the antagonistic effect of glibenclamide. We suggest that K(ATP), SK(Ca), BK(Ca) and K(V) are involved in the arachidonic acid-induced relaxation of human pulmonary arteries. Cyclooxygenase metabolites are the main relaxing agents of arachidonic acid, involving K(ATP) and SK(Ca) channels. CYP-dependent metabolites modulate arachidonic acid-induced relaxation through a pathway involving K(+) channels. K(ATP) channels are involved through a NOS-dependent pathway.
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pubmed:language |
eng
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pubmed:journal | |
pubmed:citationSubset |
IM
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pubmed:chemical | |
pubmed:status |
MEDLINE
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pubmed:month |
Oct
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pubmed:issn |
0014-2999
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pubmed:author | |
pubmed:issnType |
Print
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pubmed:day |
6
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pubmed:volume |
501
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
127-35
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pubmed:dateRevised |
2006-11-15
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pubmed:meshHeading |
pubmed-meshheading:15464071-Arachidonic Acid,
pubmed-meshheading:15464071-Dose-Response Relationship, Drug,
pubmed-meshheading:15464071-Humans,
pubmed-meshheading:15464071-Nitric Oxide,
pubmed-meshheading:15464071-Potassium Channels,
pubmed-meshheading:15464071-Pulmonary Artery,
pubmed-meshheading:15464071-Signal Transduction,
pubmed-meshheading:15464071-Vasodilation
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pubmed:year |
2004
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pubmed:articleTitle |
Arachidonic acid relaxes human pulmonary arteries through K+ channels and nitric oxide pathways.
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pubmed:affiliation |
Laboratory of Cardiovascular Physiopathology and Pharmacology, Faculty of Medicine, 7 bd. Jeanne d'Arc, BP 87900, 21079 Dijon cedex, France. Pascal.Guerard@u-bourgogne.fr
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pubmed:publicationType |
Journal Article,
Comparative Study,
In Vitro
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