title: Effects of candesartan, an angiotensin II receptor type I blocker, on atrial remodeling in spontaneously hypertensive rats.
abstract: Hypertension-induced structural remodeling of the left atrium (LA) has been suggested to involve the renin-angiotensin system. This study investigated whether treatment with an angiotensin receptor blocker, candesartan, regresses atrial remodeling in spontaneously hypertensive rats (SHR). Effects of treatment with candesartan were compared to treatment with a nonspecific vasodilatator, hydralazine. Thirty to 32-week-old adult male SHR were either untreated (n = 15) or received one of either candesartan cilexetil (n = 9; 3 mg/kg/day) or hydralazine (n = 10; 14 mg/kg/day) via their drinking water for 14 weeks prior to experiments. Untreated age- and sex-matched Wistar-Kyoto rats (WKY; n = 13) represented a normotensive control group. Untreated SHR were hypertensive, with left ventricular hypertrophy (LVH) compared to WKY, but there were no differences in systolic pressures in excised, perfused hearts. LA from SHR were hypertrophied and showed increased fibrosis compared to those from WKY, but there was no change in connexin-43 expression or phosphorylation. Treatment with candesartan reduced systolic tail artery pressures of conscious SHR below those of normotensive WKY and caused regression of both LVH and LA hypertrophy. Although hydralazine reduced SHR arterial pressures to those of WKY and led to regression of LA hypertrophy, it had no significant effect on LVH. Notably, LA fibrosis was unaffected by treatment with either agent. These data show that candesartan, at a dose sufficient to reduce blood pressure and LVH, did not cause regression of LA fibrosis in hypertensive rats. On the other hand, the data also suggest that normalization of arterial pressure can lead to the regression of LA hypertrophy.
authors: Cardiovascular Research Laboratories, School of Physiology & Pharmacology, School of Medical Sciences, University of Bristol, Bristol, U.K.
authors: Stéphanie C
authors: SC
authors: Choisy
authors: Department of Pharmacology and Toxicology, College of Veterinary Medicine, Chonbuk National University, Jeonju-City, South Korea.
authors: Shang-Jin
authors: SJ
authors: Kim
authors: Cardiovascular Research Laboratories, School of Physiology & Pharmacology, School of Medical Sciences, University of Bristol, Bristol, U.K.
authors: Jules C
authors: JC
authors: Hancox
authors: School of Biological, Biomedical and Environmental Sciences, University of Hull, Hull, U.K.
authors: Sandra A
authors: SA
authors: Jones
authors: Cardiovascular Research Laboratories, School of Physiology & Pharmacology, School of Medical Sciences, University of Bristol, Bristol, U.K.
authors: Andrew F
authors: AF
authors: James
keywords: Angiotensin receptor blocker; connexin‐43; fibrosis; gap junction
references: PLoS One. 2013 Aug 27;8(8):e72416
references: 24013508
references: J Cell Biol. 2000 Jun 26;149(7):1503-12
references: 10871288
references: Circ Res. 2009 Dec 4;105(12):1213-22
references: 19875729
references: Hypertension. 2010 Apr;55(4):918-23
references: 20194307
references: Circulation. 2009 Feb 3;119(4):606-18
references: 19188521
references: Cardiovasc Res. 2008 Oct 1;80(1):9-19
references: 18519446
references: Circ Res. 1993 Sep;73(3):413-23
references: 8348686
references: Circulation. 1995 Oct 1;92(7):1954-68
references: 7671380
references: Brain Res. 2004 Nov 26;1028(1):9-18
references: 15518636
references: Lancet. 2008 Sep 27;372(9644):1174-83
references: 18757085
references: Nature. 2002 Jan 10;415(6868):219-26
references: 11805846
references: Circulation. 1994 Feb;89(2):724-30
references: 8313561
references: Circ Arrhythm Electrophysiol. 2012 Dec;5(6):1184-92
references: 23159416
references: Hypertension. 1995 Jun;25(6):1155-60
references: 7768556
references: Lancet. 2006 Jan 21;367(9506):262-72
references: 16427496
references: J Am Coll Cardiol. 2010 Feb 2;55(5):469-80
references: 20117462
references: J Hypertens. 2008 Mar;26(3):403-11
references: 18300848
references: J Am Coll Cardiol. 2002 Nov 6;40(9):1636-44
references: 12427417
references: Prog Biophys Mol Biol. 2003 May-Jul;82(1-3):151-62
references: 12732275
references: J Physiol. 2004 Oct 15;560(Pt 2):429-37
references: 15308686
references: Exp Ther Med. 2013 Apr;5(4):1009-1016
references: 23599726
references: Am J Cardiol. 2002 Dec 15;90(12 ):1284-9
references: 12480035
references: Circ Res. 1994 May;74(5):839-51
references: 8156631
references: Basic Res Cardiol. 2007 May;102(3):245-56
references: 17268887
references: Cardiovasc Res. 1997 Jul;35(1):138-47
references: 9302358
references: J Am Coll Cardiol. 2010 May 25;55(21):2299-307
references: 20488299
references: Circ Arrhythm Electrophysiol. 2011 Oct;4(5):761-9
references: 21862733
references: Circ Res. 1995 May;76(5):892-9
references: 7729007
references: J Cell Sci. 2003 Jun 1;116(Pt 11):2203-11
references: 12697837
references: J Am Coll Cardiol. 2008 Jan 1;51(1):1-11
references: 18174029
references: Lancet. 1999 Feb 20;353(9153):611-6
references: 10030325
references: Circulation. 2008 Jan 22;117(3):344-55
references: 18172037
references: J Renin Angiotensin Aldosterone Syst. 2012 Dec;13(4):496-503
references: 22546623
references: J Mol Cell Cardiol. 2007 Aug;43(2):148-58
references: 17597147
references: Circulation. 2001 Nov 20;104(21):2608-14
references: 11714658
references: JAMA. 1994 Mar 16;271(11):840-4
references: 8114238
references: Curr Opin Cardiol. 2005 Jan;20(1):31-7
references: 15596957
references: Circulation. 1997 Nov 4;96(9):3157-63
references: 9386188
references: Pacing Clin Electrophysiol. 1997 Feb;20(2 Pt 2):397-413
references: 9058844
references: J Am Coll Cardiol. 2005 Mar 1;45(5):712-9
references: 15734615
references: Hypertens Res. 2006 Apr;29(4):277-84
references: 16778335
references: Eur Heart J. 2006 Dec;27(24):3045-56
references: 17098760
references: J Hypertens. 2008 Mar;26(3):570-82
references: 18300870
references: Regul Pept. 2010 Jun 8;162(1-3):73-8
references: 20074590
references: J Am Coll Cardiol. 2001 Sep;38(3):883-91
references: 11527649
references: J Am Coll Cardiol. 2005 Jun 7;45(11):1832-9
references: 15936615
references: Heart Rhythm. 2008 Mar;5(3):451-9
references: 18313605
references: Hypertension. 2006 Sep;48(3):443-52
references: 16847148
references: Am Heart J. 2007 Sep;154(3):448-53
references: 17719288
references: Hypertension. 2007 Mar;49(3):498-505
references: 17242301
references: Pharmacol Rev. 2013 Mar 13;65(2):809-48
references: 23487168
references: J Am Coll Cardiol. 2003 Jun 18;41(12):2197-204
references: 12821247
references: Cardiovasc Res. 2006 Oct 1;72(1):69-79
references: 16839528
references: J Am Coll Cardiol. 2008 Feb 26;51(8):802-9
references: 18294563
references: Circ Res. 2006 Jun 23;98(12):1498-505
references: 16709897
references: Lancet. 1999 Nov 20;354(9192):1751-6
references: 10577635
references: Hypertension. 2001 Oct;38(4):846-51
references: 11641297
references: J Mol Cell Cardiol. 1994 Jul;26(7):809-20
references: 7966349