title: Endothelin-1 and ET receptors impair left ventricular function by mediated coronary arteries dysfunction in chronic intermittent hypoxia rats.
abstract: Obstructive sleep apnea (OSA) results in cardiac dysfunction and vascular endothelium injury. Chronic intermittent hypoxia (CIH), the main characteristic of OSAS, is considered to be mainly responsible for cardiovascular system impairment. This study is aimed to evaluate the role of endothelin-1(ET-1) system in coronary injury and cardiac dysfunction in CIH rats. In our study, Sprague-Dawley rats were exposed to CIH (FiO29% for 1.5 min, repeated every 3 min for 8 h/d, 7 days/week for 3 weeks). After 3 weeks, the left ventricular developed pressure (LVDP) and coronary resistance (CR) were measured with the langendorff mode in isolated hearts. Meanwhile, expressions of ET-1 and ET receptors were detected by immunohistochemical and western blot, histological changes were also observed to determine effects of CIH on coronary endothelial cells. Results suggested that decreased LVDP level combined with augmented coronary resistance was exist in CIH rats. CIH could induce endothelial injury and endothelium-dependent vasodilatation dysfunction in the coronary arteries. Furthermore, ET-1 and ETAreceptor expressions in coronary vessels were increased after CIH exposure, whereas ETBreceptors expression was decreased. Coronary contractile response to ET-1 in both normoxia and CIH rats was inhibited by ETAreceptor antagonist BQ123. However, ETBreceptor antagonist BQ788 enhanced ET-1-induced contractile in normoxia group, but had no significant effects on CIH group. These results indicate that CIH-induced cardiac dysfunction may be associated with coronary injury. ET-1 plays an important role in coronary pathogenesis of CIH through ETAreceptor by mediating a potent vasoconstrictor response. Moreover, decreased ETBreceptor expression that leads to endothelium-dependent vasodilatation decline, might be also participated in coronary and cardiac dysfunction.
authors.affiliation: Department of Physiology, Hebei University of Chinese Medicine, Shijiazhuang, Hebei, China.
authors.forename: Jin-Wei
authors.initials: JW
authors.lastname: Wang
authors.affiliation: Department of Biochemistry, Hebei University of Chinese Medicine, Shijiazhuang, Hebei, China.
authors.forename: Ai-Ying
authors.initials: AY
authors.lastname: Li
authors.affiliation: Department of Pharmacology, Hebei University of Chinese Medicine, Shijiazhuang, Hebei, China.
authors.forename: Qiu-Hong
authors.initials: QH
authors.lastname: Guo
authors.affiliation: Department of Physiology, Hebei University of Chinese Medicine, Shijiazhuang, Hebei, China.
authors.forename: Ya-Jing
authors.initials: YJ
authors.lastname: Guo
authors.affiliation: Division of Pulmonary, Critical Care and Sleep Medicine, Beth Israel Deaconess Medical Center, Boston, Massachusetts.
authors.forename: James W
authors.initials: JW
authors.lastname: Weiss
authors.affiliation: Department of Physiology, Hebei University of Chinese Medicine, Shijiazhuang, Hebei, China jesphy@126.com.
authors.forename: En-Sheng
authors.initials: ES
authors.lastname: Ji
mesh_terms: D000818:Animals; D003331:Coronary Vessels / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology*; D065128:Endothelin Receptor Antagonists / Q000008:administration & dosage / Q000494:pharmacology*; D019332:Endothelin-1 / Q000008:administration & dosage / Q000378:metabolism / Q000494:pharmacology*; D004730:Endothelium, Vascular / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D006352:Heart Ventricles / Q000473:pathology / Q000503:physiopathology*; D000860:Hypoxia / Q000150:complications / Q000378:metabolism* / Q000503:physiopathology / Q000662:veterinary; D008297:Male; D009200:Myocardial Contraction / Q000187:drug effects / Q000276:immunology; D009842:Oligopeptides / Q000008:administration & dosage / Q000494:pharmacology; D010456:Peptides, Cyclic / Q000008:administration & dosage / Q000494:pharmacology; D010880:Piperidines / Q000008:administration & dosage / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D017466:Receptors, Endothelin / Q000378:metabolism*; D020181:Sleep Apnea, Obstructive / Q000150:complications / Q000378:metabolism / Q000503:physiopathology; D014664:Vasodilation / Q000187:drug effects / Q000502:physiology; D018487:Ventricular Dysfunction, Left / Q000139:chemically induced* / Q000473:pathology / Q000503:physiopathology
chemical_list: D065128:Endothelin Receptor Antagonists; D019332:Endothelin-1; D009842:Oligopeptides; D010456:Peptides, Cyclic; D010880:Piperidines; D017466:Receptors, Endothelin; C086539:BQ 788; C072247:cyclo(Trp-Asp-Pro-Val-Leu)
keywords: Cardiac function; chronic intermittent hypoxia; coronary resistance; endothelial receptors; endothelin‐1