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A novel opener of small and intermediate calcium-activated K channels releases NO and causes EDHF type vasodilatation in rat mesenteric arteries / E. Stankevicius, C. Krøjgaard, B. Rinno, E. Boedtkjer, O. Schjørring, K. Litvin, A. Hughes, U. Simonsen
Type of publication
Konferencijų tezės nerecenzuojamame leidinyje / Conference theses in non-peer-reviewed publication (T2)
Author(s)
Department of Pharmacology,University of Aarhus, Denmark | |
Krøjgaard, Christel | Pharmacology, University of Aarhus, Denmark |
Rinno, B | Pharmacology, University of Aarhus, Denmark |
Boedtkjer, Ebbe | Pharmacology, University of Aarhus, Denmark |
Schjorring, Olav | Pharmacology, University of Aarhus, Denmark |
Litvin, Kristina | Pharmacology, University of Aarhus, Denmark |
Hughes, Alun D | Department of Clinical Pharmacology, Imperial College, UK |
Simonsen, Ulf | Department of Pharmacology, University of Aarhus, Aarhus, Denmark |
Title
A novel opener of small and intermediate calcium-activated K channels releases NO and causes EDHF type vasodilatation in rat mesenteric arteries / E. Stankevicius, C. Krøjgaard, B. Rinno, E. Boedtkjer, O. Schjørring, K. Litvin, A. Hughes, U. Simonsen
Date Issued
Date Issued |
---|
2008-05-15 |
Extent
p. 17, poster 3.
Is part of
The Annual Meeting of The Danish Society of Pharmacology and Toxicology : 15-16 May 2008 : meeting programme / Danish Society for Pharmacology and Toxicology. Aarhus : University of Aarhus, 2008.
Version
Originalus / Original
Series/Report no.
Posters
Field of Science
Abstract
The present study addressed whether NS309 (6,7-dichloro-1H-indole-2,3-dione 3-oxime) acts on calcium-activated K (KCa) channels and leads to release of NO and EDHF-type relaxation. Quantitative PCR and patch clamp studies were performed in HUVEC. Vasorelaxation and release of NO studied in rat mesenteric arteries. Quantitative PCR showed expression of small (SKCa) and intermediate (IKCa) conductance KCa, while expression of large-conductance (BKCa) KCa was below detection limit in primary human umbilical vein endothelial cells. In whole cell patch clamp studies, NS309 (1-1000 nM) induced calcium-dependent increases in current which were inhibited in the presence of blockers of SKCa, apamin, of IKCa, charybdotoxin and TRAM-34, while a blocker of BKCa, iberiotoxin, and a blocker of KATP channels, glibenclamide, did not change NS309- evoked increases in current. In the presence of indomethacin and contracted with NA, NS309 evoked endothelium and concentration-dependent relaxations which were inhibited in the presence of an inhibitor of NOS, asymmetric dimethylarginine (ADMA, 300 μM). Microsensor detection of NO revealed NS309 increased NO concentration. These increases in NO were inhibited by combination of apamin and charybdotoxin. In pressurized rat mesenteric small arteries contracted with U46619, NS309 evoked endothelium-dependent vasodilatation was enhanced in the presence of ADMA and inhibited by apamin, charybdotoxin, and TARM-34, while iberiotoxin did not alter vasodilatation. A combination of ADMA, apamin, and charybdotoxin abolished NS309 vasodilatation. The present findings support NS309 is an opener of SKCa and IKCa channels and leads to endothelium-dependent vasorelaxation associated with release of NO in rat superior mesenteric artery, while EDHF is involved in vasodilatation of mesenteric small arteries.
Type of document
type::text::conference output::conference proceedings::conference paper
Other Identifier(s)
(LSMU ALMA)990000708080107106
Coverage Spatial
Danija / Denmark (DK)
Language
Anglų / English (en)