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PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
5
pubmed:dateCreated
2007-7-16
pubmed:abstractText
The radial artery (RA) is used as a spastic coronary bypass graft. This study was designed to investigate the mechanism of vasorelaxant effects of YC-1 (3-(5'-hydroxymethyl-2'-furyl)-1-benzyl indazole), a nitric oxide (NO)-independent soluble guanylate cyclase (sGC) activator, and DEA/NO (diethylamine/nitric oxide), a NO-nucleophile adduct, on the human RA. RA segments (n = 25) were obtained from coronary artery bypass grafting patients and were divided into 3-4 mm vascular rings. Using the isolated tissue bath technique, the endothelium-independent vasodilatation function was tested in vitro by the addition of cumulative concentrations of YC-1 (10-10 to 3 x 10-7 mol/L) and DEA/NO (10-8 to 3 x 10-5 mol/L) following vasocontraction by phenylephrine in the presence or absence of 10-5 mol/L ODQ (1H-(1,2,4)oxadiazole(4,3-a)quinoxalin-1-one), the selective sGC inhibitor, 10-7 mol/L iberiotoxin, a blocker of Ca2+-activated K+ channels, or 10-5 mol/L ODQ plus 10-7 mol/L iberiotoxin. We also evaluated the effect of YC-1 and DEA/NO on the cGMP levels in vascular rings obtained from human radial artery (n = 6 for each drug). YC-1 (10-10 to 3 x 10-7 mol/L) and DEA/NO (10-8 to 3 x 10-5 mol/L) caused the concentration-dependent vasorelaxation in RA rings precontracted with phenylephrine (10-5 mol/L) (n = 20 for each drug). Pre-incubation of RA rings with ODQ, iberiotoxin, or ODQ plus iberiotoxin significantly inhibited the vasorelaxant effect of YC-1, but the inhibitor effect of ODQ plus iberiotoxin was significantly more than that of ODQ and iberiotoxin alone (p < 0.05). The vasorelaxant effect of DEA/NO almost completely abolished in the presence of ODQ and iberiotoxin plus ODQ, but did not significantly change in the presence of iberiotoxin alone (p > 0.05). The pEC50 value of DEA/NO was significantly lower than those for YC-1 (p < 0.01), with no change Emax values in RA rings. In addition, YC-1-stimulated RA rings showed more elevation in cGMP than that of DEA/NO (p < 0.05). These findings indicate that YC-1 is a more potent relaxant than DEA/NO in the human RA. The relaxant effects of YC-1 could be due to the stimulation of the sGC and Ca2+-sensitive K+channels, whereas the relaxant effects of DEA/NO could be completely due to the stimulation of the sGC. YC-1 and DEA/NO may be effective as vasodilator for the short-term treatment of perioperative spasm of coronary bypass grafts.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
http://linkedlifedata.com/resource/pubmed/chemical/1,1-diethyl-2-hydroxy-2-nitrosohydra..., http://linkedlifedata.com/resource/pubmed/chemical/1H-(1,2,4)oxadiazolo(4,3-a)quinoxali..., http://linkedlifedata.com/resource/pubmed/chemical/3-(5'-hydroxymethyl-2'-furyl)-1-benz..., http://linkedlifedata.com/resource/pubmed/chemical/Cyclic GMP, http://linkedlifedata.com/resource/pubmed/chemical/Enzyme Activators, http://linkedlifedata.com/resource/pubmed/chemical/Enzyme Inhibitors, http://linkedlifedata.com/resource/pubmed/chemical/Hydrazines, http://linkedlifedata.com/resource/pubmed/chemical/Indazoles, http://linkedlifedata.com/resource/pubmed/chemical/Nitric Oxide Donors, http://linkedlifedata.com/resource/pubmed/chemical/Oxadiazoles, http://linkedlifedata.com/resource/pubmed/chemical/Peptides, http://linkedlifedata.com/resource/pubmed/chemical/Phenylephrine, http://linkedlifedata.com/resource/pubmed/chemical/Potassium Channels..., http://linkedlifedata.com/resource/pubmed/chemical/Quinoxalines, http://linkedlifedata.com/resource/pubmed/chemical/Vasoconstrictor Agents, http://linkedlifedata.com/resource/pubmed/chemical/iberiotoxin
pubmed:status
MEDLINE
pubmed:month
May
pubmed:issn
0008-4212
pubmed:author
pubmed:issnType
Print
pubmed:volume
85
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
521-6
pubmed:dateRevised
2009-11-3
pubmed:meshHeading
pubmed-meshheading:17632587-Aged, pubmed-meshheading:17632587-Analysis of Variance, pubmed-meshheading:17632587-Coronary Artery Bypass, pubmed-meshheading:17632587-Cyclic GMP, pubmed-meshheading:17632587-Dose-Response Relationship, Drug, pubmed-meshheading:17632587-Enzyme Activators, pubmed-meshheading:17632587-Enzyme Inhibitors, pubmed-meshheading:17632587-Female, pubmed-meshheading:17632587-Humans, pubmed-meshheading:17632587-Hydrazines, pubmed-meshheading:17632587-Indazoles, pubmed-meshheading:17632587-Male, pubmed-meshheading:17632587-Middle Aged, pubmed-meshheading:17632587-Nitric Oxide Donors, pubmed-meshheading:17632587-Oxadiazoles, pubmed-meshheading:17632587-Peptides, pubmed-meshheading:17632587-Phenylephrine, pubmed-meshheading:17632587-Potassium Channels, Calcium-Activated, pubmed-meshheading:17632587-Quinoxalines, pubmed-meshheading:17632587-Radial Artery, pubmed-meshheading:17632587-Vasoconstrictor Agents, pubmed-meshheading:17632587-Vasodilation
pubmed:year
2007
pubmed:articleTitle
Investigation of the vasorelaxant effects of 3-(5'-hydroxymethyl-2'-furyl)-1-benzyl indazole (YC-1) and diethylamine/nitric oxide (DEA/NO) on the human radial artery used as coronary bypass graft.
pubmed:affiliation
Department of Cardiovascular Surgery, Cumhuriyet University School of Medicine, 58140 Sivas, Turkey. oberkan@cumhuriyet.edu.tr
pubmed:publicationType
Journal Article, In Vitro