Universität zu Köln

Behmenburg, Friederike, Pickert, Eileen, Mathes, Alexander, Heinen, Andre, Hollmann, Markus W., Huhn, Ragnar and Berger, Marc M. (2017). The Cardioprotective Effect of Dexmedetomidine in Rats Is Dose-Dependent and Mediated by BKCa Channels. J. Cardiovasc. Pharmacol., 69 (4). S. 228 - 236. PHILADELPHIA: LIPPINCOTT WILLIAMS & WILKINS. ISSN 1533-4023

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Abstract

The alpha-2 receptor agonist Dexmedetomidine (Dex) protects the heart against ischemia-reperfusion injury. We investigated the signaling cascade underlying Dex-induced acute cardio-protection, with special emphasis on large-conductance Ca2 +-sensitive potassium (BKCa) channels. Rats were anesthetized with pentobarbital. Hearts were isolated, mounted on a Langendorff system and perfused with Krebs-Henseleit buffer. Hearts underwent 33 minutes of ischemia followed by 60 minutes of reperfusion. Before the beginning of ischemia, Dex was administered at different doses (0.1-30 nM) for characterization of a dose-effect relationship. In another set of experiments, Dex (3 nM) was administered together with the BKCa channel inhibitor paxilline and the connexin-43 inhibitor peptide Gap27. Also, the BKCa channel opener NS1619 was administered. In control animals, infarct size was 49% +/- 5%. Dex at 3-30 nM reduced infarct size to similar to 22%, whereas lower (0.1-1 nM) doses reduced infarct size to similar to 38%. Paxilline (1 mu M)and GAP27 (6 mu M) blocked the Dex-induced cardioprotection. NS1619 (10 mu M) reduced infarct size to about the same magnitude as did the higher doses of Dex. Functional heart parameters and coronary flow were not different between the study groups. In male rats, the Dex-induced protection against ischemia-reperfusion injury involves connexin-43 and activation of BKCa channels.

Item Type:	Journal Article
Creators:	Creators Email ORCID ORCID Put Code Behmenburg, Friederike UNSPECIFIED UNSPECIFIED UNSPECIFIED Pickert, Eileen UNSPECIFIED UNSPECIFIED UNSPECIFIED Mathes, Alexander UNSPECIFIED UNSPECIFIED UNSPECIFIED Heinen, Andre UNSPECIFIED UNSPECIFIED UNSPECIFIED Hollmann, Markus W. UNSPECIFIED UNSPECIFIED UNSPECIFIED Huhn, Ragnar UNSPECIFIED UNSPECIFIED UNSPECIFIED Berger, Marc M. UNSPECIFIED UNSPECIFIED UNSPECIFIED
URN:	urn:nbn:de:hbz:38-234987
DOI:	10.1097/FJC.0000000000000466
Journal or Publication Title:	J. Cardiovasc. Pharmacol.
Volume:	69
Number:	4
Page Range:	S. 228 - 236
Date:	2017
Publisher:	LIPPINCOTT WILLIAMS & WILKINS
Place of Publication:	PHILADELPHIA
ISSN:	1533-4023
Language:	English
Faculty:	Unspecified
Divisions:	Unspecified
Subjects:	no entry
Uncontrolled Keywords:	Keywords Language CA2+-ACTIVATED K+ CHANNELS; ISCHEMIA-REPERFUSION INJURY; ISCHEMIA/REPERFUSION INJURY; MYOCARDIAL-ISCHEMIA; ACTIVATION; PROTECTS; MECHANISM; INHIBITION; HEART; PHOSPHORYLATION Multiple languages Cardiac & Cardiovascular Systems; Pharmacology & Pharmacy Multiple languages
Refereed:	Yes
URI:	http://kups.ub.uni-koeln.de/id/eprint/23498