Intermittent Hypoxia-Induced Carotid Body Chemosensory Potentiation and Hypertension Are Critically Dependent on Peroxynitrite Formation

作者: Esteban A. Moya , Paulina Arias , Carlos Varela , María P. Oyarce , Rodrigo Del Rio

DOI: 10.1155/2016/9802136

关键词: Carotid bodyPeroxynitriteBiochemistryPeroxynitrous acidBlood pressureEndocrinologyHypoxia (medical)Internal medicineEbselenIntermittent hypoxiaMedicineOxidative stress

摘要: Oxidative stress is involved in the development of carotid body (CB) chemosensory potentiation and systemic hypertension induced by chronic intermittent hypoxia (CIH), main feature obstructive sleep apnea. We tested whether peroxynitrite (ONOO−), a highly reactive nitrogen species, enhanced CB oxygen chemosensitivity during CIH. Accordingly, we studied effects Ebselen, an ONOO− scavenger, on 3-nitrotyrosine immunoreactivity (3-NT-ir) CB, discharge, arterial blood pressure (BP) rats exposed to Male Sprague-Dawley were CIH (5% O2, 12 times/h, 8 h/day) for 7 days. Ebselen (10 mg/kg/day) was administrated using osmotic minipumps BP measured with radiotelemetry. Compared sham animals, CIH-treated showed increased 3-NT-ir within responses hypoxia, response acute hypertension. Rats treated displayed significant reduction levels (60.8 ± 14.9 versus 22.9 4.2 a.u.), reduced 5% O2 (266.5 13.4 168.6 16.8 Hz), decreased mean (116.9 13.2 82.1 5.1 mmHg). Our results suggest that CIH-induced are critically dependent formation.

参考文章(46)
Joshi John, Ming-Fung Wu, Nigel T. Maidment, Hoa A. Lam, Lisa N. Boehmer, Melanie Patton, Jerome M. Siegel, Developmental changes in CSF hypocretin-1 (orexin-A) levels in normal and genetically narcoleptic Doberman pinschers. The Journal of Physiology. ,vol. 560, pp. 587- 592 ,(2004) , 10.1113/JPHYSIOL.2004.070573
Rodrigo Iturriaga, Esteban A. Moya, Rodrigo Del Rio, Inflammation and oxidative stress during intermittent hypoxia: the impact on chemoreception. Experimental Physiology. ,vol. 100, pp. 149- 155 ,(2015) , 10.1113/EXPPHYSIOL.2014.079525
J. S. Beckman, W. H. Koppenol, Nitric oxide, superoxide, and peroxynitrite: the good, the bad, and ugly. American Journal of Physiology-cell Physiology. ,vol. 271, ,(1996) , 10.1152/AJPCELL.1996.271.5.C1424
David Gozal, Leila Kheirandish-Gozal, Cardiovascular morbidity in obstructive sleep apnea: oxidative stress, inflammation, and much more. American Journal of Respiratory and Critical Care Medicine. ,vol. 177, pp. 369- 375 ,(2008) , 10.1164/RCCM.200608-1190PP
Rodrigo Iturriaga, Esteban A Moya, Rodrigo Del Rio, Carotid body potentiation induced by intermittent hypoxia: implications for cardiorespiratory changes induced by sleep apnoea. Clinical and Experimental Pharmacology and Physiology. ,vol. 36, pp. 1197- 1204 ,(2009) , 10.1111/J.1440-1681.2009.05213.X
Rodrigo Iturriaga, David C Andrade, Rodrigo Del Rio, None, Enhanced carotid body chemosensory activity and the cardiovascular alterations induced by intermittent hypoxia Frontiers in Physiology. ,vol. 5, pp. 468- 468 ,(2014) , 10.3389/FPHYS.2014.00468
Fumiyuki Yamakura, Hiroaki Kawasaki, Post-translational modifications of superoxide dismutase Biochimica et Biophysica Acta. ,vol. 1804, pp. 318- 325 ,(2010) , 10.1016/J.BBAPAP.2009.10.010
Gajendra Kumar Azad, Raghuvir S. Tomar, Ebselen, a promising antioxidant drug: mechanisms of action and targets of biological pathways Molecular Biology Reports. ,vol. 41, pp. 4865- 4879 ,(2014) , 10.1007/S11033-014-3417-X
Andreas Daiber, Ming-Hui Zou, Markus Bachschmid, Volker Ullrich, Ebselen as a peroxynitrite scavenger in vitro and ex vivo. Biochemical Pharmacology. ,vol. 59, pp. 153- 160 ,(2000) , 10.1016/S0006-2952(99)00309-3