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Impact of Mitochondrial Ca2+-Sensitive Potassium (mBKCa) Channels in Sildenafil-Induced Cardioprotection in Rats.

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Title: Impact of Mitochondrial Ca2+-Sensitive Potassium (mBKCa) Channels in Sildenafil-Induced Cardioprotection in Rats.
Authors: Friederike Behmenburg, Marianne Dorsch, Ragnar Huhn, David Mally, André Heinen, Markus W Hollmann, Marc M Berger
Source: PLoS ONE, Vol 10, Iss 12, p e0144737 (2015)
Publisher Information: Public Library of Science (PLoS), 2015.
Publication Year: 2015
Collection: LCC:Medicine
LCC:Science
Subject Terms: Medicine, Science
More Details: BackgroundMitochondrial large-conductance Ca2+-sensitive potassium (mBKCa) channels are involved in myocardial ischemic preconditioning. Their role in sildenafil-induced cardioprotection is unknown. We investigated whether sildenafil-induced acute cardioprotection is mediated by activation of mBKCa channels in the rat heart in vitro.MethodsMale Wistar rats (n = 8 per group) were randomized and anesthetized with pentobarbital (90 mg/kg). Hearts were isolated, mounted on a Langendorff system and perfused with Krebs-Henseleit buffer at a constant pressure of 80 mmHg. Hearts underwent 30 min of global ischemia followed by 60 min of reperfusion. At the end of the experiments infarct size was determined by TTC staining. In the control group rats were not further treated. Sildenafil (3 μM) was administered over 10 min before the beginning of ischemia. The mBKCa channel inhibitor paxilline (1 μM) was administered with and without sildenafil before the onset of ischemia. The pathway underlying sildenafil-induced cardioprotection was further investigated with the protein kinase G blocker KT5823 (1 μM). Myocardial cGMP concentration was measured by ELISA. Data (mean±SD) were analysed with a one and two-way analysis of variance as appropriate.ResultsIn control animals infarct size was 52±8%. Sildenafil increased cGMP concentration and reduced infarct size to 35±6% (PConclusionThis study shows that in male rats protein kinase G-dependent opening of mBKCa channels plays a pivotal role in sildenafil-induced cardioprotection.
Document Type: article
File Description: electronic resource
Language: English
ISSN: 1932-6203
Relation: https://journals.plos.org/plosone/article/file?id=10.1371/journal.pone.0144737&type=printable; https://doaj.org/toc/1932-6203
DOI: 10.1371/journal.pone.0144737&type=printable
DOI: 10.1371/journal.pone.0144737
Access URL: https://doaj.org/article/bb44a6350e8b49e38e5ba66df8ed6029
Accession Number: edsdoj.bb44a6350e8b49e38e5ba66df8ed6029
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  Data: Impact of Mitochondrial Ca2+-Sensitive Potassium (mBKCa) Channels in Sildenafil-Induced Cardioprotection in Rats.
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  Data: PLoS ONE, Vol 10, Iss 12, p e0144737 (2015)
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  Data: BackgroundMitochondrial large-conductance Ca2+-sensitive potassium (mBKCa) channels are involved in myocardial ischemic preconditioning. Their role in sildenafil-induced cardioprotection is unknown. We investigated whether sildenafil-induced acute cardioprotection is mediated by activation of mBKCa channels in the rat heart in vitro.MethodsMale Wistar rats (n = 8 per group) were randomized and anesthetized with pentobarbital (90 mg/kg). Hearts were isolated, mounted on a Langendorff system and perfused with Krebs-Henseleit buffer at a constant pressure of 80 mmHg. Hearts underwent 30 min of global ischemia followed by 60 min of reperfusion. At the end of the experiments infarct size was determined by TTC staining. In the control group rats were not further treated. Sildenafil (3 μM) was administered over 10 min before the beginning of ischemia. The mBKCa channel inhibitor paxilline (1 μM) was administered with and without sildenafil before the onset of ischemia. The pathway underlying sildenafil-induced cardioprotection was further investigated with the protein kinase G blocker KT5823 (1 μM). Myocardial cGMP concentration was measured by ELISA. Data (mean±SD) were analysed with a one and two-way analysis of variance as appropriate.ResultsIn control animals infarct size was 52±8%. Sildenafil increased cGMP concentration and reduced infarct size to 35±6% (PConclusionThis study shows that in male rats protein kinase G-dependent opening of mBKCa channels plays a pivotal role in sildenafil-induced cardioprotection.
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