Effect of endothelin receptor antagonists on gap junction channels in post-infarcted rats

Tsung-Ming Lee, Chien-Chang Chen, Nen-Chung Chang

Research output: Contribution to journalArticle

Abstract

Myocardial infarction leads to derangements in cellular electrical stability and the generation of lethal arrhythmias. Endothelin (ET) receptor blockers (ERAs) have been shown to contribute to the antiarrhythmic effect. We investigated whether ERAs exert antiarrhythmic effects through increased expression of connexin43 (Cx43) after infarction. Twenty-four hours after ligation of the left anterior descending artery, male Wistar rats received either vehicle, ABT-627 (selective ETA receptor antagonist), bosentan (nonselective ETA/ETB receptor antagonist), or hydralazine for 4 weeks. Measurement of myocardial ET-1 levels at the border zone revealed a significant increase in vehicle-treated rats compared with sham-operated rats, consistent with increased ET-1 levels after infarction. Immunoblotting revealed that at the border zone the vehicle group showed a marked reduction in the amount of phosphorylated Cx43, whereas either ABT-627- or bosentan-treated groups showed only a slight reduction compared with sham. Immunohistochemistry and real-time RT-PCR confirmed that the Cx43 attenuation was prevented by ERA administration. Arrhythmic scores during programmed stimulation in ERA-treated rats were significantly lower than those treated with vehicle. The effects of ERAs on Cx43 and arrhythmais were dissociated from their blood pressure-lowering effect because ERAs and hydralazine reduced arterial pressure similarly. Our data indicate that the ET system plays an important role in the attenuated expression of Cx43 after infarction. Chronic inhibition of either ETA or ETA/ETB receptors restores the decreased expression of phosphorylated Cx43 and improves electrical instability.
Original languageEnglish
Pages (from-to)1130.16
JournalFASEB Journal
Volume22
Publication statusPublished - Apr 1 2008

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Connexin 43
Gap Junctions
Rats
Infarction
Hydralazine
Endothelin-1
Endothelin Receptors
Pressure effects
Endothelins
Blood pressure
Immunoblotting
Ligation
Endothelin Receptor Antagonists
Wistar Rats
Cardiac Arrhythmias
Real-Time Polymerase Chain Reaction
Arterial Pressure
Arteries
Immunohistochemistry
Myocardial Infarction

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Effect of endothelin receptor antagonists on gap junction channels in post-infarcted rats. / Lee, Tsung-Ming; Chen, Chien-Chang; Chang, Nen-Chung.

In: FASEB Journal, Vol. 22, 01.04.2008, p. 1130.16.

Research output: Contribution to journalArticle

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