title: Effects of cyclic intermittent hypoxia on ET-1 responsiveness and endothelial dysfunction of pulmonary arteries in rats.
abstract: Obstructive sleep apnoea (OSA) is a risk factor for cardiovascular disorders and in some cases is complication of pulmonary hypertension. We simulated OSA by exposing rats to cyclic intermittent hypoxia (CIH) to investigate its effect on pulmonary vascular endothelial dysfunction. Sprague-Dawley Rats were exposed to CIH (FiO2 9% for 1 min, repeated every 2 min for 8 h/day, 7 days/wk for 3 wk), and the pulmonary arteries of normoxia and CIH treated rats were analyzed for expression of endothelin-1 (ET-1) and ET receptors by histological, immunohistochemical, RT-PCR and Western Blot analyses, as well as for contractility in response to ET-1. In the pulmonary arteries, ET-1 expression was increased, and ET-1 more potently elicited constriction of the pulmonary artery in CIH rats than in normoxic rats. Exposure to CIH induced marked endothelial cell damage associated with a functional decrease of endothelium-dependent vasodilatation in the pulmonary artery. Compared with normoxic rats, ETA receptor expression was increased in smooth muscle cells of the CIH rats, while the expression of ETB receptors was decreased in endothelial cells. These results demonstrated endothelium-dependent vasodilation was impaired and the vasoconstrictor responsiveness increased by CIH. The increased responsiveness to ET-1 induced by intermittent hypoxia in pulmonary arteries of rats was due to increased expression of ETA receptors predominantly, meanwhile, decreased expression of ETB receptors in the endothelium may also participate in it.
authors.affiliation: Department of Physiology, Hebei Medical University, Shijiazhuang, Hebei, People's Republic of China.
authors.forename: Zhuo
authors.initials: Z
authors.lastname: Wang
authors.forename: Ai-Ying
authors.initials: AY
authors.lastname: Li
authors.forename: Qiu-Hong
authors.initials: QH
authors.lastname: Guo
authors.forename: Jian-Ping
authors.initials: JP
authors.lastname: Zhang
authors.forename: Qi
authors.initials: Q
authors.lastname: An
authors.forename: Ya-jing
authors.initials: YJ
authors.lastname: Guo
authors.forename: Li
authors.initials: L
authors.lastname: Chu
authors.forename: J Woodrow
authors.initials: JW
authors.lastname: Weiss
authors.forename: En-Sheng
authors.initials: ES
authors.lastname: Ji
mesh_terms: D000818:Animals; D019332:Endothelin-1 / Q000096:biosynthesis*; D004730:Endothelium, Vascular / Q000378:metabolism* / Q000473:pathology / Q000503:physiopathology; D005786:Gene Expression Regulation; D006976:Hypertension, Pulmonary / Q000209:etiology / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology; D000860:Hypoxia / Q000150:complications / Q000378:metabolism* / Q000473:pathology / Q000503:physiopathology; D008297:Male; D011651:Pulmonary Artery / Q000378:metabolism* / Q000473:pathology / Q000503:physiopathology; D051381:Rats; D017207:Rats, Sprague-Dawley; D017466:Receptors, Endothelin / Q000096:biosynthesis; D020181:Sleep Apnea, Obstructive / Q000150:complications / Q000378:metabolism* / Q000473:pathology / Q000503:physiopathology; D014661:Vasoconstriction; D014664:Vasodilation
chemical_list: D019332:Endothelin-1; D017466:Receptors, Endothelin
references.citation: Exp Physiol. 2007 Jan;92(1):21-6
references.pmid: 17124275
references.citation: Br J Pharmacol. 1994 Dec;113(4):1257-62
references.pmid: 7889281
references.citation: Circulation. 2003 Jul 8;108(1):9-12
references.pmid: 12847053
references.citation: Pharmacol Rev. 1994 Sep;46(3):325-415
references.pmid: 7831383
references.citation: Circulation. 2000 Nov 21;102(21):2607-10
references.pmid: 11085964
references.citation: Am J Physiol Heart Circ Physiol. 2003 Dec;285(6):H2797-803
references.pmid: 12907424
references.citation: Annu Rev Physiol. 1999;61:391-415
references.pmid: 10099694
references.citation: Life Sci. 1992;50(10):677-82
references.pmid: 1738296
references.citation: J Clin Invest. 1993 Apr;91(4):1367-73
references.pmid: 7682570
references.citation: Prog Cardiovasc Dis. 2009 Mar-Apr;51(5):363-70
references.pmid: 19249442
references.citation: Biochem Biophys Res Commun. 1994 Mar 30;199(3):1461-5
references.pmid: 8147891
references.citation: JAMA. 2003 Oct 8;290(14):1906-14
references.pmid: 14532320
references.citation: J Hypertens. 1999 Jan;17(1):61-6
references.pmid: 10100095
references.citation: N Engl J Med. 1993 Apr 29;328(17):1230-5
references.pmid: 8464434
references.citation: Am J Physiol. 1995 Dec;269(6 Pt 2):H1988-97
references.pmid: 8594908
references.citation: J Appl Physiol (1985). 2000 Aug;89(2):493-8
references.pmid: 10926630
references.citation: Biochem Biophys Res Commun. 1992 Apr 15;184(1):518-24
references.pmid: 1567454
references.citation: Mol Cell Biochem. 2000 May;208(1-2):53-62
references.pmid: 10939628
references.citation: Proc Natl Acad Sci U S A. 1988 Dec;85(24):9797-800
references.pmid: 3059352
references.citation: Circulation. 1991 Feb;83(2):701-3
references.pmid: 1750863
references.citation: Br J Pharmacol. 1999 Oct;128(3):809-15
references.pmid: 10516666
references.citation: Vascul Pharmacol. 2011 Nov-Dec;55(5-6):163-8
references.pmid: 21864717
references.citation: Pharmacology. 1997 Dec;55(6):299-308
references.pmid: 9413859
references.citation: Circulation. 2004 Jan 20;109(2):159-65
references.pmid: 14734504
references.citation: Cardiovasc Res. 2007 Oct 1;76(1):8-18
references.pmid: 17617392
references.citation: Hypertension. 1999 Oct;34(4 Pt 2):876-81
references.pmid: 10523377
references.citation: Hypertension. 2001 Feb;37(2 Pt 2):511-5
references.pmid: 11230327
references.citation: Circulation. 1995 Feb 15;91(4):1229-35
references.pmid: 7850963
references.citation: Am J Physiol Heart Circ Physiol. 2008 Feb;294(2):H920-7
references.pmid: 18083893
references.citation: Am Heart J. 1998 Apr;135(4):614-20
references.pmid: 9539476
references.citation: Heart Dis. 2002 Sep-Oct;4(5):296-305
references.pmid: 12350242
references.citation: J Clin Invest. 1990 Feb;85(2):587-90
references.pmid: 2153712
references.citation: Clin Invest Med. 1991 Dec;14(6):600-6
references.pmid: 1665404
references.citation: Hypertension. 2005 Apr;45(4):705-9
references.pmid: 15738350
references.citation: Am J Respir Cell Mol Biol. 1999 Apr;20(4):620-30
references.pmid: 10100993
references.citation: J Appl Physiol (1985). 2009 Jan;106(1):259-67
references.pmid: 18927268
references.citation: Curr Med Chem. 2010;17(11):1059-66
references.pmid: 20156159
references.citation: Br J Pharmacol. 1999 Jan;126(1):219-26
references.pmid: 10051139
references.citation: Cardiovasc Res. 1997 Jan;33(1):196-200
references.pmid: 9059544
references.citation: J Cardiovasc Pharmacol. 1994 May;23(5):838-45
references.pmid: 7521470
references.citation: Am J Physiol. 1997 Feb;272(2 Pt 1):L287-93
references.pmid: 9124380
references.citation: Pharmacol Rev. 2002 Jun;54(2):219-26
references.pmid: 12037137
references.citation: Int J Biochem Cell Biol. 2002 Dec;34(12):1508-12
references.pmid: 12379270