title: [Effects of valsartan and U0126 on atrial fibrosis and connexin40 remodeling in rats].
abstract: OBJECTIVE
  To explore the effects of valsartan and MEK1/2 inhibitor U0126 on atrial fibrosis and connexin40 (Cx40) remodeling in rats treated with isoproterenol (ISO).
  
  
  METHODS
  32 male SD rats were randomly divided into control group (A), ISO (5 mg · kg(-1) · d(-1) for 7 days) + DMSO group (B), ISO + U0126 (0.5 mg · kg(-1) · d(-1) for 28 days) group (C, U0126 was dissolved in DMSO), ISO + valsartan (30 mg · kg(-1) · d(-1) for 28 days) + DMSO group (D). Rats were sacrificed after 28 days. The AngIIcontent in myocardial tissue was measured by radioimmunoassay, P-MEK1/2, P-ERK1/2 and Cx40 was detected by immunohistochemistry, atrial fibrosis was determined on HE and Masson stained heart sections.
  
  
  RESULTS
  The content of AngII was significantly higher in group B, C and D compared with group A [(368.243 ± 6.283) ng/L, (357.175 ± 5.944) ng/L, (359.908 ± 2.496) ng/L vs (250.380 ± 4.261) ng/L, P < 0.01]; the degree of atrial fibrosis was significantly lower in group C and D compared with group B [CVF(10.260 ± 0.525)%, (10.238 ± 0.524)% vs (78.710 ± 1.587)%, P < 0.01] while there was no atrial fibrosis in group A [CVF(9.025 ± 0.456)%]; the expression of P-MEK1/2 and P-ERK1/2 was significantly upregulated in group B compared with group A (P-MEK1/2: 0.311 ± 0.007 vs 0.203 ± 0.009, P < 0.01; P-ERK1/2: 0.259 ± 0.003 vs 0.173 ± 0.006, P < 0.01) and significantly lower in group C and D compared with group B (P-MEK1/2: 0.212 ± 0.004, 0.213 ± 0.005 vs 0.311 ± 0.007, P < 0.01, P-ERK1/2: 0.178 ± 0.004, 0.175 ± 0.007 vs 0.259 ± 0.003, P < 0.01). The content of Cx40 was obviously reduced and the distribution of Cx40 was disordered in group B compared with A (0.199 ± 0.007 vs 0.241 ± 0.004, P < 0.01) which could be partly reversed in group C and D (0.239 ± 0.037, 0.235 ± 0.006 vs 0.199 ± 0.007, P < 0.01). All parameters in group C and D were similar (P > 0.05).
  
  
  CONCLUSIONS
  The chronically elevated AngII content in myocardium may be related to atrial fibrosis and Cx40 remodeling in this model, valsartan and U0126 were equivalent on attenuating atrial fibrosis and Cx40 remodeling by inhibiting ERK pathways at different levels.
authors.affiliation: The Cardiology Department of Lanzhou General Hospital of Lanzhou Military Area Command of Chinese PLA, Lanzhou 730050, China. zhangzwz@medmail.com.cn
authors.forename: Wei-ze
authors.initials: WZ
authors.lastname: Zhang
authors.forename: Zhi-gang
authors.initials: ZG
authors.lastname: Wang
authors.forename: Yong-qing
authors.initials: YQ
authors.lastname: Chen
authors.forename: Ling
authors.initials: L
authors.lastname: Ma
authors.forename: Tao
authors.initials: T
authors.lastname: Li
authors.forename: Hong-gang
authors.initials: HG
authors.lastname: Bao
authors.forename: Pei-hong
authors.initials: PH
authors.lastname: Li
mesh_terms: D000818:Animals; D002070:Butadienes / Q000494:pharmacology*; D017630:Connexins / Q000378:metabolism*; D005355:Fibrosis; D006325:Heart Atria / Q000378:metabolism / Q000473:pathology*; D008297:Male; D009206:Myocardium / Q000378:metabolism / Q000473:pathology*; D009570:Nitriles / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D013777:Tetrazoles / Q000494:pharmacology*; D014633:Valine / Q000031:analogs & derivatives* / Q000494:pharmacology; D000068756:Valsartan; D000097003:Gap Junction alpha-5 Protein
chemical_list: D002070:Butadienes; D017630:Connexins; D009570:Nitriles; D013777:Tetrazoles; D014633:Valine; D000068756:Valsartan; D000097003:Gap Junction alpha-5 Protein; C113580:U 0126