Switch to
| Predicate | Object |
|---|---|
| rdf:type | |
| lifeskim:mentions | |
| pubmed:issue |
3
|
| pubmed:dateCreated |
1993-10-14
|
| pubmed:abstractText |
A series of compounds have been reported which open the large conductance calcium activated potassium channel (maxi-K). By utilizing the most potent compound, NS-004 [1-(5-chloro-2-hydroxyphenyl)-5-trifluromethyl-1,3-dihydro-2-be nzimidazol-2- one], we studied the role of maxi-K channels in ischemic myocardium. Isolated rat hearts were pretreated with vehicle or NS-004 (6-36 microM). NS-004 caused a concentration-dependent reduction in left ventricular developed pressure and an increase in coronary flow. In global ischemia (25 min), a concentration-dependent increase in time to contracture was found in NS-004 (6-20 microM)-treated hearts (EC25 = 8.6 microM). Neither iberiotoxin (50 nM), a maxi-K blocker, nor glyburide (1 microM), an adenosine triphosphate-sensitive potassium channel blocker, reversed the preischemic or ischemic effects of 20 microM NS-004. NS-004 relaxed phenylephrine- and KCl- contracted rat aortic smooth muscle (IC50 = 9.2 microM). This relaxation was unaffected by 50 and 200 nM iberiotoxin. Whole cell potassium currents in ventricular myocytes demonstrated no significant increases in outward potassium current after treatment with NS-004 (1-20 microM). A small, but significant, increase in outward potassium current was observed with 50 microM NS-004. When peak inward L-type calcium currents were measured in ventricular myocytes, a concentration-dependent inhibition was observed in the presence of NS-004 (1-50 microM). Iberiotoxin (50 nM) did not alter the inhibition of inward calcium current observed in the presence of NS-004.(ABSTRACT TRUNCATED AT 250 WORDS)
|
| pubmed:language |
eng
|
| pubmed:journal | |
| pubmed:citationSubset |
IM
|
| pubmed:chemical | |
| pubmed:status |
MEDLINE
|
| pubmed:month |
Sep
|
| pubmed:issn |
0022-3565
|
| pubmed:author | |
| pubmed:issnType |
Print
|
| pubmed:volume |
266
|
| pubmed:owner |
NLM
|
| pubmed:authorsComplete |
Y
|
| pubmed:pagination |
1422-9
|
| pubmed:dateRevised |
2008-11-21
|
| pubmed:meshHeading |
pubmed-meshheading:8371147-Animals,
pubmed-meshheading:8371147-Aorta, Thoracic,
pubmed-meshheading:8371147-Benzimidazoles,
pubmed-meshheading:8371147-Calcium,
pubmed-meshheading:8371147-Chlorophenols,
pubmed-meshheading:8371147-Dogs,
pubmed-meshheading:8371147-Electrophysiology,
pubmed-meshheading:8371147-Guinea Pigs,
pubmed-meshheading:8371147-Heart,
pubmed-meshheading:8371147-Heart Conduction System,
pubmed-meshheading:8371147-Heart Ventricles,
pubmed-meshheading:8371147-Male,
pubmed-meshheading:8371147-Models, Biological,
pubmed-meshheading:8371147-Muscle, Smooth, Vascular,
pubmed-meshheading:8371147-Myocardial Contraction,
pubmed-meshheading:8371147-Myocardial Ischemia,
pubmed-meshheading:8371147-Neural Conduction,
pubmed-meshheading:8371147-Potassium Channels,
pubmed-meshheading:8371147-Rats,
pubmed-meshheading:8371147-Rats, Inbred WKY,
pubmed-meshheading:8371147-Rats, Sprague-Dawley,
pubmed-meshheading:8371147-Ventricular Function
|
| pubmed:year |
1993
|
| pubmed:articleTitle |
The cardioprotective, vasorelaxant and electrophysiological profile of the large conductance calcium-activated potassium channel opener NS-004.
|
| pubmed:affiliation |
Bristol-Myers Squibb Pharmaceutical Research Institute, Department of Cardiovascular Pharmacology, Princeton, New Jersey.
|
| pubmed:publicationType |
Journal Article,
In Vitro
|