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PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
1-3
pubmed:dateCreated
2004-10-6
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.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Oct
pubmed:issn
0014-2999
pubmed:author
pubmed:issnType
Print
pubmed:day
6
pubmed:volume
501
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
127-35
pubmed:dateRevised
2006-11-15
pubmed:meshHeading
pubmed:year
2004
pubmed:articleTitle
Arachidonic acid relaxes human pulmonary arteries through K+ channels and nitric oxide pathways.
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
pubmed:publicationType
Journal Article, Comparative Study, In Vitro