Research Article Endothelinergic Contractile Hyperreactivity in Rat Contralateral Carotid to Balloon Injury: Integrated Role for ET B Receptors and Superoxide Anion Larissa Pernomian, 1 Lilian R. Gimenes, 2 Mayara S. Gomes, 3 Bruno N. do Vale, 4 Cristina R. B. Cardoso, 1 Ana M. de Oliveira, 3 and Josimar D. Moreira 5 1 Department of Biosciences Applied to Pharmacy, Faculty of Pharmaceutical Sciences of Ribeir˜ ao Preto, University of S˜ ao Paulo, Ribeir˜ ao Preto, SP, Brazil 2 Department of Pharmacology, Faculty of Medicine of Ribeir˜ ao Preto, University of S˜ ao Paulo, SP, Brazil 3 Department of Physics and Chemistry, Faculty of Pharmaceutical Sciences of Ribeir˜ ao Preto, University of S˜ ao Paulo, Ribeir˜ ao Preto, SP, Brazil 4 Department of Pharmacy, University Center UnirG, Gurupi, TO, Brazil 5 Department of Clinical and Toxicological Analysis, Faculty of Pharmacy, Federal University of Minas Gerais, Belo Horizonte, MG, Brazil Correspondence should be addressed to Larissa Pernomian; l.pernomian@usp.br Received 3 April 2017; Revised 8 June 2017; Accepted 2 July 2017; Published 14 September 2017 Academic Editor: Fabrizio Montecucco Copyright © 2017 Larissa Pernomian et al. Tis is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. Temporal consequences of neurocompensation to balloon injury on endothelinergic functionality in rat contralateral carotid were evaluated. Rats underwent balloon injury in lef carotid and were treated with CP-96345 (NK 1 antagonist). Concentration-response curves for endothelin-1 were obtained in contralateral (right) carotid at 2, 8, 16, 30, or 45 days afer surgery in the absence or presence of BQ-123 (ET A antagonist), BQ-788 (ET B antagonist), or Tempol (superoxide-dismutase mimic). Endothelin-1-induced calcium mobilization was evaluated in functional assays carried out with BQ-123, BQ-788, or Tempol. Endothelin-1-induced NADPH oxidase-driven superoxide generation was measured by lucigenin chemiluminescence assays performed with BQ-123 or BQ-788. Endothelin-1-induced contraction was increased in contralateral carotid from the sixteenth day afer surgery. Tis response was restored in CP-96345-treated rats. Endothelium removal or BQ-123 did not change endothelin-1-induced contraction in contralateral carotid. Tis response was restored by BQ-788 or Tempol. Contralateral carotid exhibited an increased endothelin- 1-induced calcium mobilization, which was restored by BQ-788 or Tempol. Contralateral carotid exhibited an increased endothelin- 1-induced lucigenin chemiluminescence, which was restored by BQ-788. We conclude that the NK 1 -mediated neurocompensatory response to balloon injury elicits a contractile hyperreactivity to endothelin-1 in rat contralateral carotid by enhancing the muscular ET B -mediated NADPH oxidase-driven generation of superoxide, which activates calcium channels. 1. Introduction Vascular remodeling is a hallmark of many vascular disorders including atherosclerosis [1, 2]. Carotid occlusive disease is a specifc kind of atherosclerosis that signifcantly contributes to cerebrovascular accidents [3]. In turn, stroke represents one of the main leading causes of the mortality assigned to cardiovascular diseases, which account for 7.6 million of deaths annually [4]. Balloon angioplasty is the most common intervention to restore blood fow upon arterial obstruction by atheroscle- rotic plaques [5–7]. However, therapeutic efcacy of balloon angioplasty is limited by postoperative complications mainly resultant from restenosis, which markedly narrows ipsilateral (injured) artery lumen and reduces local blood fow [8, 9]. Pathophysiological mechanisms underlying restenosis have been efectively studied by the rat carotid balloon injury model, which triggers neointimal formation in close Hindawi BioMed Research International Volume 2017, Article ID 3137580, 13 pages https://doi.org/10.1155/2017/3137580