title: Captopril reduces cardiac inflammatory markers in spontaneously hypertensive rats by inactivation of NF-kB.
abstract: BACKGROUND
  Captopril is an angiotensin-converting enzyme (ACE) inhibitor widely used in the treatment of arterial hypertension and cardiovascular diseases. Our objective was to study whether captopril is able to attenuate the cardiac inflammatory process associated with arterial hypertension.
  
  
  METHODS
  Left ventricle mRNA expression and plasma levels of pro-inflammatory (interleukin-1beta (IL-1beta) and IL-6) and anti-inflammatory (IL-10) cytokines, were measured in spontaneously hypertensive rats (SHR) and their control normotensive, Wistar-Kyoto (WKY) rats, with or without a 12-week treatment with captopril (80 mg/Kg/day; n = six animals per group). To understand the mechanisms involved in the effect of captopril, mRNA expression of ACE, angiotensin II type I receptor (AT1R) and p22phox (a subunit of NADPH oxidase), as well as NF-kappaB activation and expression, were measured in the left ventricle of these animals.
  
  
  RESULTS
  In SHR, the observed increases in blood pressures, heart rate, left ventricle relative weight, plasma levels and cardiac mRNA expression of IL-1beta and IL-6, as well as the reductions in the plasma levels and in the cardiac mRNA expression of IL-10, were reversed after the treatment with captopril. Moreover, the mRNA expressions of ACE, AT1R and p22phox, which were enhanced in the left ventricle of SHR, were reduced to normal values after captopril treatment. Finally, SHR presented an elevated cardiac mRNA expression and activation of the transcription nuclear factor, NF-kappaB, accompanied by a reduced expression of its inhibitor, IkappaB; captopril administration corrected the observed changes in all these parameters.
  
  
  CONCLUSIONS
  These findings show that captopril decreases the inflammation process in the left ventricle of hypertensive rats and suggest that NF-kappaB-driven inflammatory reactivity might be responsible for this effect through an inactivation of NF-kappaB-dependent pro-inflammatory factors.
authors.affiliation: Departamento de Fisiología y Zoología, Facultad de Farmacia, Universidad de Sevilla, E-41012 Sevilla, Spain. vazquez@us.es.
authors.forename: José L
authors.initials: JL
authors.lastname: Miguel-Carrasco
authors.forename: Sonia
authors.initials: S
authors.lastname: Zambrano
authors.forename: Antonio J
authors.initials: AJ
authors.lastname: Blanca
authors.forename: Alfonso
authors.initials: A
authors.lastname: Mate
authors.forename: Carmen M
authors.initials: CM
authors.lastname: Vázquez
references.citation: Immunopharmacol Immunotoxicol. 1995 Aug;17(3):471-91
references.pmid: 8576541
references.citation: Hypertension. 2007 Mar;49(3):695-703
references.pmid: 17283252
references.citation: Am J Physiol Heart Circ Physiol. 2008 Mar;294(3):H1226-32
references.pmid: 18178715
references.citation: Eur J Pharmacol. 2010 Feb 10;627(1-3):242-50
references.pmid: 19903466
references.citation: Circulation. 1997 Dec 2;96(11):4002-10
references.pmid: 9403625
references.citation: Cell Immunol. 2010;260(2):92-7
references.pmid: 19854435
references.citation: Am J Physiol Regul Integr Comp Physiol. 2000 Mar;278(3):R572-7
references.pmid: 10712274
references.citation: Eur J Pharmacol. 2010 Apr 25;632(1-3):65-72
references.pmid: 20123095
references.citation: J Am Coll Cardiol. 2004 Jul 21;44(2):362-8
references.pmid: 15261932
references.citation: Curr Hypertens Rep. 2002 Apr;4(2):167-71
references.pmid: 11884273
references.citation: Circ Res. 2007 Sep 28;101(7):734-41
references.pmid: 17673672
references.citation: J Hypertens Suppl. 2009 Aug;27(6):S5-10
references.pmid: 19633453
references.citation: Hypertension. 2000 Jul;36(1):103-9
references.pmid: 10904020
references.citation: Kidney Int. 2008 Feb;73(3):288-99
references.pmid: 18033243
references.citation: Sheng Li Xue Bao. 2006 Aug 25;58(4):318-23
references.pmid: 16906331
references.citation: J Biol Chem. 2004 May 7;279(19):20363-8
references.pmid: 15001568
references.citation: Am J Physiol Regul Integr Comp Physiol. 2006 Dec;291(6):R1817-24
references.pmid: 16840655
references.citation: Hypertension. 2000 Jan;35(1 Pt 2):193-201
references.pmid: 10642297
references.citation: Hypertension. 1996 Jan;27(1):14-8
references.pmid: 8591877
references.citation: Hypertens Res. 2007 May;30(5):451-7
references.pmid: 17587757
references.citation: Circulation. 2002 May 14;105(19):2296-302
references.pmid: 12010913
references.citation: Hypertension. 2003 Feb;41(2):266-73
references.pmid: 12574093
references.citation: Hypertension. 2009 Sep;54(3):619-24
references.pmid: 19620507
references.citation: J Mol Cell Cardiol. 2006 Oct;41(4):580-91
references.pmid: 16949095
references.citation: Hypertension. 2005 Oct;46(4):943-7
references.pmid: 16087785
references.citation: Am J Physiol Heart Circ Physiol. 2005 Jan;288(1):H111-5
references.pmid: 15308481
references.citation: Exp Physiol. 1999 Nov;84(6):1095-105
references.pmid: 10564706
references.citation: Kidney Int. 2006 Jul;70(1):170-6
references.pmid: 16710350
references.citation: Circulation. 2005 Oct 18;112(16):2436-45
references.pmid: 16216963
references.citation: Physiol Res. 2000;49(1):1-10
references.pmid: 10805399
references.citation: Exp Eye Res. 2006 Sep;83(3):651-7
references.pmid: 16698015
references.citation: Curr Opin Nephrol Hypertens. 2006 Mar;15(2):152-8
references.pmid: 16481882
references.citation: Hypertension. 1997 Dec;30(6):1621-7
references.pmid: 9403592
references.citation: J Lab Clin Med. 1993 Oct;122(4):395-403
references.pmid: 8228553
references.citation: Kidney Int. 1997 Oct;52(4):926-33
references.pmid: 9328931
references.citation: Biochem Biophys Res Commun. 2002 Aug 9;296(1):194-200
references.pmid: 12147250
references.citation: Biochem Biophys Res Commun. 1999 Apr 21;257(3):826-8
references.pmid: 10208867
references.citation: Am J Pathol. 1998 Dec;153(6):1825-37
references.pmid: 9846973
references.citation: Am J Physiol Regul Integr Comp Physiol. 2006 Sep;291(3):R760-7
references.pmid: 16690767
references.citation: Circulation. 2000 Oct 31;102(18):2243-8
references.pmid: 11056100
references.citation: Mol Cell Biochem. 2000 Sep;212(1-2):155-69
references.pmid: 11108147
references.citation: Hypertension. 1999 Jan;33(1 Pt 2):212-8
references.pmid: 9931107
references.citation: J Hypertens. 1993 Jun;11(6):611-22
references.pmid: 8397240
references.citation: J Cell Physiol. 2003 Jun;195(3):402-10
references.pmid: 12704649
references.citation: J Hypertens. 2005 Feb;23(2):435-44
references.pmid: 15662233
references.citation: Regul Pept. 2005 Aug 15;130(1-2):67-74
references.pmid: 15908024
references.citation: J Hypertens Suppl. 2009 Aug;27(6):S42-6
references.pmid: 19633451
references.citation: Clin Sci (Lond). 2007 Jun;112(7):375-84
references.pmid: 17324119
references.citation: J Hypertens. 2009 Mar;27(3):626-32
references.pmid: 19262230
references.citation: Redox Rep. 2004;9(6):354-9
references.pmid: 15720832
references.citation: Am J Hypertens. 2008 Nov;21(11):1231-7
references.pmid: 18787523
references.citation: Circ Res. 1999 Oct 15;85(8):e17-24
references.pmid: 10521249
references.citation: Toxicol Appl Pharmacol. 2000 Oct 15;168(2):123-30
references.pmid: 11032767
references.citation: Asian J Surg. 2002 Jul;25(3):203-8
references.pmid: 12376215
references.citation: Nat Protoc. 2006;1(2):581-5
references.pmid: 17406285
references.citation: Cardiovasc Pathol. 2004 Mar-Apr;13(2):71-8
references.pmid: 15033155
references.citation: Diabetes. 2002 Jun;51(6):1931-7
references.pmid: 12031983
references.citation: Eur J Clin Invest. 2001 Jan;31(1):31-6
references.pmid: 11168436
references.citation: J Mol Cell Cardiol. 1997 Dec;29(12):3365-74
references.pmid: 9441842
references.citation: Circulation. 1999 Sep 14;100(11):1223-9
references.pmid: 10484544
references.citation: J Mol Cell Cardiol. 2000 Feb;32(2):177-85
references.pmid: 10722795