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Medientyp:
E-Artikel
Titel:
Inhibition of EDHF by two new combinations of K+‐channel inhibitors in rat isolated mesenteric arteries
Beteiligte:
Hinton, Jane M;
Langton, Philip D
Erschienen:
Wiley, 2003
Erschienen in:
British Journal of Pharmacology, 138 (2003) 6, Seite 1031-1035
Sprache:
Englisch
DOI:
10.1038/sj.bjp.0705171
ISSN:
0007-1188;
1476-5381
Entstehung:
Anmerkungen:
Beschreibung:
It is widely established that in rat mesenteric arteries, endothelium‐derived hyperpolarizing factor (EDHF)‐mediated relaxation evoked by acetylcholine is abolished by a combination of charybdotoxin plus apamin. 4‐Aminopyridine, an inhibitor of voltage‐gated (Kv) K+‐channels, in combination with apamin had moderate effects on the EDHF‐mediated relaxation. Maurotoxin (MTX), an inhibitor of Kv and intermediate‐conductance Ca2+‐activated K+‐channels (IK), had no effect on EDHF‐mediated relaxation. However, MTX in combination with apamin completely abolished EDHF‐mediated relaxation and endothelial cell hyperpolarization. The selective IK inhibitor 2‐(2‐chlorophenyl)‐2,2‐diphenyl acetonitrile (TRAM‐39) had no significant effect on EDHF‐mediated relaxation. EDHF‐mediated vasorelaxation and hyperpolarization was abolished by a combination of TRAM‐39 and apamin. These data demonstrate two new combinations of K+‐channel inhibitors for the investigation of EDHF. Furthermore, by using TRAM‐39, a potent selective inhibitor of IK channels, we provide the first direct evidence that abolition of EDHF requires the simultaneous presence of intermediate‐ and small‐conductance Ca2+‐activated K+‐channel inhibitors.British Journal of Pharmacology (2003) 138, 1031–1035. doi:10.1038/sj.bjp.0705171