title: Rho-kinase inhibitor Y-27632 attenuates pulmonary hypertension in hyperoxia-exposed newborn rats.
abstract: OBJECTIVE
  To test the hypothesis that neonatal hyperoxia induced pulmonary hypertension accompanied by increased Rho-kinase expression in rat lungs and that Rho-kinase inhibitor could attenuate right ventricular hypertrophy and pulmonary arterial remodeling.
  
  
  METHODS
  Newborn rats were exposed to >95% O2 in the first week after birth, then to 60% O2 in the following 2 weeks. Control pups were exposed to room air over the same periods. The pups were injected with either Rho-kinase inhibitor Y-27632 (10 mg·kg(-1)·d(-1), ip) or vehicle from postnatal d 14 to 20. Lung and heart tissues were collected on postnatal d 7 and 21. Rho-kinase activity in lungs was measured using Western blotting and immunohistochemistry. The right ventricular hypertrophy and arterial medial wall thickness (MWT) were assessed morphologically.
  
  
  RESULTS
  Rho-kinase activity in lungs was comparable between the hyperoxic and control pups on postnatal d 7, but it had a more than 2-fold increase in the hyperoxic pups on postnatal d 21. Moreover, the hyperoxic exposure induced structural features of pulmonary hypertension, as shown by the right ventricular hypertrophy and significantly increased arterial MWT. Administration with Y-27632 effectively blocked the hyperoxia-induced increase of Rho-kinase activity in lungs, and attenuated the right ventricular hypertrophy.
  
  
  CONCLUSIONS
  Rho-kinase inhibitor may be a novel therapy for attenuating the hyperoxia-induced structural changes in pulmonary hypertension.
authors: Department of Anatomy, School of Medicine, College of Medicine, Taipei Medical University, Taipei, Taiwan, China.
authors: Hsiu-Chu
authors: HC
authors: Chou
authors: Liang-Ti
authors: LT
authors: Huang
authors: Tsu-Fu
authors: TF
authors: Yeh
authors: Chung-Ming
authors: CM
authors: Chen
mesh_terms: D000577:Amides / Q000494:pharmacology*; D000818:Animals; D000831:Animals, Newborn; D000959:Antihypertensive Agents / Q000494:pharmacology*; D015153:Blotting, Western; D004195:Disease Models, Animal; D005260:Female; D018496:Hyperoxia / Q000150:complications; D006976:Hypertension, Pulmonary / Q000188:drug therapy* / Q000503:physiopathology; D017380:Hypertrophy, Right Ventricular / Q000188:drug therapy / Q000503:physiopathology; D008297:Male; D011725:Pyridines / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D013997:Time Factors; D054460:rho-Associated Kinases / Q000037:antagonists & inhibitors* / Q000235:genetics / Q000378:metabolism
chemical_list: D000577:Amides; D000959:Antihypertensive Agents; D011725:Pyridines; C108830:Y 27632; D054460:rho-Associated Kinases
references: Am J Physiol Heart Circ Physiol. 2010 Dec;299(6):H1854-64
references: 20889845
references: J Cardiovasc Pharmacol. 2007 Feb;49(2):85-9
references: 17312448
references: Pediatr Res. 2012 Nov;72(5):468-78
references: 22926548
references: Respir Res. 2009 Apr 29;10:30
references: 19402887
references: Br J Pharmacol. 2009 Nov;158(5):1285-94
references: 19814724
references: Am J Physiol Heart Circ Physiol. 2004 Oct;287(4):H1495-500
references: 15371261
references: Pediatr Res. 2010 Dec;68(6):519-25
references: 20805789
references: Trends Pharmacol Sci. 2006 Feb;27(2):97-104
references: 16376997
references: Dev Biol. 2004 Jan 1;265(1):23-32
references: 14697350
references: Anat Rec. 1974 Sep;180(1):77-98
references: 4416419
references: Am J Physiol Lung Cell Mol Physiol. 2009 Nov;297(5):L920-30
references: 19749000
references: Drug News Perspect. 2006 Nov;19(9):517-22
references: 17220956
references: Am J Physiol Lung Cell Mol Physiol. 2004 Oct;287(4):L665-72
references: 12959926
references: Neonatology. 2012;101(1):47-54
references: 21791939
references: Am J Respir Crit Care Med. 2005 Sep 15;172(6):750-6
references: 15947285
references: Acta Pharmacol Sin. 2011 Feb;32(2):217-22
references: 21217769
references: Circ Res. 2007 Mar 30;100(6):923-9
references: 17332430
references: Expert Rev Cardiovasc Ther. 2005 May;3(3):441-51
references: 15889972
references: J Ethnopharmacol. 2012 Dec 18;144(3):761-7
references: 23123267
references: J Appl Physiol (1985). 2003 Jun;94(6):2303-12
references: 12562676
references: Eur J Pharmacol. 2003 Jan 26;460(1):51-7
references: 12535859
references: Am J Physiol Lung Cell Mol Physiol. 2008 Jul;295(1):L71-8
references: 18469113
references: Pediatr Res. 2010 Feb;67(2):177-82
references: 19858775
references: Neonatology. 2009;95(4):299-305
references: 19052476
references: J Appl Physiol (1985). 2001 Jul;91(1):497-503
references: 11408468
references: EMBO J. 1996 May 1;15(9):2208-16
references: 8641286
references: Antioxid Redox Signal. 2003 Dec;5(6):759-69
references: 14588149
references: Exp Cell Res. 2000 Nov 25;261(1):44-51
references: 11082274
references: Pediatr Res. 1996 Jun;39(6):921-9
references: 8725250