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This Article Full Text Full Text (PDF) All Versions of this Article: 294/4/H1871    most recent 01129.2007v1 Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in Web of Science Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Web of Science (3) Citing Articles via Google Scholar Google Scholar Articles by Lee, T.-M. Articles by Chang, N.-C. Search for Related Content PubMed PubMed Citation Articles by Lee, T.-M. Articles by Chang, N.-C.

Effect of endothelin receptor antagonists on ventricular susceptibility in postinfarcted rats

¹Cardiology Section, Department of Medicine, Taipei Medical University and Chi-Mei Medical Center; ²Cardiology Section, Department of Surgery, Chi-Mei Medical Center; ³Department of Pharmacy, National Taiwan University and Hospital; ⁴Cardiology Section, Department of Medicine, Taipei Medical University and Hospital, Taipei, Taiwan

Submitted 29 September 2007 ; accepted in final form 11 February 2008

This study investigated whether selective endothelin (ET) type A (ET_A) or nonselective ET_A/ET_B receptor blockade exerted antiarrhythmic effects through attenuated sympathetic reinnervation after infarction. Twenty-four hours after ligation of the left anterior descending artery, male Wistar rats received either vehicle, ABT-627 (selective ET_A receptor antagonist), bosentan (nonselective ET_A/ET_B receptor antagonist), or hydralazine for 4 wk. The measurement of myocardial ET-1 levels at the remote zone revealed a significant increase in vehicle-treated infarcted rats compared with sham-operated rats, consistent with increased activities of ET-1 after infarction. Sympathetic nerve function changes assessed by the norepinephrine content of myocardium and the dialysate and plasma dihydroxyphenylglycol levels were parallel to ET-1 levels. Immunohistochemical analysis for tyrosine hydroxylase, growth-associated protein 43, and neurofilament also confirmed the change of nerve function. This was accompanied with a significant upregulation of nerve growth factor protein expression and mRNA in the vehicle-treated infarcted rats, which reduced after the administration of either ET_A or ET_A/ET_B blockade to a similar extent. The beneficial effects of ET receptor antagonists on sympathetic nerve function and structures were dissociated from their blood pressure-lowering effect because ET receptor antagonists and hydralazine reduced arterial pressure similarly. Arrhythmic severity during programmed stimulation in ET receptor antagonists-treated rats was significantly lower than that in vehicle-treated infarcted rats. Our data indicate that the ET system, especially via ET_A receptors, plays an important role in attenuating sympathetic reinnervation after infarction. Independent of their hemodynamic effects, a chronic use of either ET_A or ET_A/ET_B antagonists may modify the arrhythmogenic response to programmed electrical stimulation.

myocardial infarction; nerve growth factor; rats; sympathetic reinnervation

This article has been cited by other articles:

				T.-M. Lee, C.-C. Chen, and N.-C. Chang Granulocyte colony-stimulating factor increases sympathetic reinnervation and the arrhythmogenic response to programmed electrical stimulation after myocardial infarction in rats Am J Physiol Heart Circ Physiol, August 1, 2009; 297(2): H512 - H522. [Abstract] [Full Text] [PDF]

				C.-S. Kang, C.-C. Chen, C.-C. Lin, N.-C. Chang, and T.-M. Lee Effect of ATP-sensitive potassium channel agonists on sympathetic hyperinnervation in postinfarcted rat hearts Am J Physiol Heart Circ Physiol, June 1, 2009; 296(6): H1949 - H1959. [Abstract] [Full Text] [PDF]