Linked Life Data

15288583

Source:http://linkedlifedata.com/resource/pubmed/id/15288583

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
1-3
pubmed:dateCreated
2004-8-3
pubmed:abstractText
Amiodarone, a powerful antiarrhythmic compound, possesses coronary and peripheral vasodilator properties. The mechanisms responsible for these effects remain incompletely understood. In the present study, the coronary effects of amiodarone and dronedarone, a non-iodinated amiodarone-like compound, were investigated in isolated guinea pig hearts perfused at constant flow with high K+ solution (40 mM). Amiodarone (0.01-10 microM), dronedarone (0.01-1 microM) and verapamil (0.01-10 microM) induced concentration-dependent decreases in coronary perfusion pressure. Amiodarone- and dronedarone-mediated reductions in coronary perfusion pressure were not modified by a cyclooxygenase inhibitor, indomethacin (3 microM). L-Nitro-L-arginine (L-NOARG; 3-100 microM) caused a rightward shift of concentration-response curves to amiodarone and dronedarone in a dose-dependent way; L-arginine, a nitric oxide (NO) precursor, reversed this effect. Furthermore, when guinea pigs were treated with NG-nitro-L-arginine methyl ester (L-NAME; 20 mg/kg), amiodarone could not reduce coronary perfusion pressure. NO synthase inhibition did not affect the coronary perfusion pressure response to verapamil. 1H-[1,2,4]Oxadiazole (4,3-a) quinoxalin-1-one (ODQ), a specific inhibitor of the guanylyl cyclase, inhibited the effects of amiodarone but not those of verapamil. In the presence of L-NOARG and ODQ, and in hearts from animals treated with L-NAME, a decrease in coronary perfusion pressure was still observed at the highest concentration of dronedarone. These results show that, in guinea pig hearts, the coronary vasodilation induced by amiodarone highly depends on nitric oxide. Dronedarone differs from amiodarone by a remaining relaxant effect, refractory to inhibition of NO synthase pathway, probably due to its Ca+ antagonist properties.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Aug
pubmed:issn
0014-2999
pubmed:author
pubmed:issnType
Print
pubmed:day
2
pubmed:volume
496
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
119-27
pubmed:dateRevised
2006-11-15
pubmed:meshHeading
pubmed:year
2004
pubmed:articleTitle
Involvement of nitric oxide in amiodarone- and dronedarone-induced coronary vasodilation in guinea pig heart.
pubmed:affiliation
Cardiovascular Thrombosis Department, Sanofi-Synthelabo Recherche, 371, rue du Pr. J. Blayac, 34184, Montpellier cedex 04, France. pierre.guiraudou@sanofi-synthelabo.com
pubmed:publicationType
Journal Article, Comparative Study, In Vitro