Tags

Type your tag names separated by a space and hit enter

Angiotensin II receptor blockade and myocardial fibrosis of the infarcted rat heart.
J Lab Clin Med. 1997 Apr; 129(4):439-46.JL

Abstract

Tissue angiotensin II (AngII) is increased in the infarcted rat heart, where it may have autocrine or paracrine properties that influence cellular protein synthesis and growth and therefore tissue repair. It was our hypothesis that treatment with an AT1 receptor antagonist would attenuate fibrous tissue formation after myocardial infarction (MI). To investigate a role for local AngII in the regulation of connective tissue formation during early and late wound healing that follows MI, this study was undertaken. Animals were randomized into two groups in which rats were or were not treated with the AT1 receptor antagonist losartan (10 mg x kg(-1) daily gavage). At 1 and 4 weeks after experimental MI was induced by coronary artery ligation, rat hearts were examined. Infarct size, infarct area, and collagen volume fraction at the site of infarction and in noninfarcted myocardium were determined by picrosirius red staining with videodensitometry. Quantitative in vitro autoradiography was used to detect AngII receptor binding density ((125)I-(Sar1,Ile8)AngII). Compared with an untreated MI control group, in losartan-treated rats we found (1) infarct size was comparable in both groups at weeks 1 and 4, (2) infarct area was comparable between groups at week 1 but was significantly reduced (p < 0.05) at week 4 in losartan-treated rats, (3) a detectable reduction in collagen volume fraction at the site of MI was not found at week 1 but was reduced (p < 0.05) at remote sites at week 4, (4) AngII receptor binding density was reduced (p < 0.05) by 50% at the site of MI at both weeks 1 and 4 in keeping with delivery of losartan to this site of injury. Thus AT1 receptor antagonism appears to influence late phase wound healing at and remote to the site of MI and suggests an association between AngII and the fibrogenic response that appears in the injured rat heart. Although still speculative, an attenuation in fibrosis after MI may account for less ventricular dysfunction and geometric remodeling of right and left ventricles and ventricular arrhythmias that have been observed in such rats treated with angiotensin converting enzyme inhibitor or AT1 receptor antagonist.

Authors+Show Affiliations

Department of Internal Medicine, University of Missouri Health Sciences Center, Columbia 65212, USA.No affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't
Research Support, U.S. Gov't, P.H.S.

Language

eng

PubMed ID

9104887

Citation

De Carvalho Frimm, C, et al. "Angiotensin II Receptor Blockade and Myocardial Fibrosis of the Infarcted Rat Heart." The Journal of Laboratory and Clinical Medicine, vol. 129, no. 4, 1997, pp. 439-46.
De Carvalho Frimm C, Sun Y, Weber KT. Angiotensin II receptor blockade and myocardial fibrosis of the infarcted rat heart. J Lab Clin Med. 1997;129(4):439-46.
De Carvalho Frimm, C., Sun, Y., & Weber, K. T. (1997). Angiotensin II receptor blockade and myocardial fibrosis of the infarcted rat heart. The Journal of Laboratory and Clinical Medicine, 129(4), 439-46.
De Carvalho Frimm C, Sun Y, Weber KT. Angiotensin II Receptor Blockade and Myocardial Fibrosis of the Infarcted Rat Heart. J Lab Clin Med. 1997;129(4):439-46. PubMed PMID: 9104887.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Angiotensin II receptor blockade and myocardial fibrosis of the infarcted rat heart. AU - De Carvalho Frimm,C, AU - Sun,Y, AU - Weber,K T, PY - 1997/4/1/pubmed PY - 1997/4/1/medline PY - 1997/4/1/entrez SP - 439 EP - 46 JF - The Journal of laboratory and clinical medicine JO - J Lab Clin Med VL - 129 IS - 4 N2 - Tissue angiotensin II (AngII) is increased in the infarcted rat heart, where it may have autocrine or paracrine properties that influence cellular protein synthesis and growth and therefore tissue repair. It was our hypothesis that treatment with an AT1 receptor antagonist would attenuate fibrous tissue formation after myocardial infarction (MI). To investigate a role for local AngII in the regulation of connective tissue formation during early and late wound healing that follows MI, this study was undertaken. Animals were randomized into two groups in which rats were or were not treated with the AT1 receptor antagonist losartan (10 mg x kg(-1) daily gavage). At 1 and 4 weeks after experimental MI was induced by coronary artery ligation, rat hearts were examined. Infarct size, infarct area, and collagen volume fraction at the site of infarction and in noninfarcted myocardium were determined by picrosirius red staining with videodensitometry. Quantitative in vitro autoradiography was used to detect AngII receptor binding density ((125)I-(Sar1,Ile8)AngII). Compared with an untreated MI control group, in losartan-treated rats we found (1) infarct size was comparable in both groups at weeks 1 and 4, (2) infarct area was comparable between groups at week 1 but was significantly reduced (p < 0.05) at week 4 in losartan-treated rats, (3) a detectable reduction in collagen volume fraction at the site of MI was not found at week 1 but was reduced (p < 0.05) at remote sites at week 4, (4) AngII receptor binding density was reduced (p < 0.05) by 50% at the site of MI at both weeks 1 and 4 in keeping with delivery of losartan to this site of injury. Thus AT1 receptor antagonism appears to influence late phase wound healing at and remote to the site of MI and suggests an association between AngII and the fibrogenic response that appears in the injured rat heart. Although still speculative, an attenuation in fibrosis after MI may account for less ventricular dysfunction and geometric remodeling of right and left ventricles and ventricular arrhythmias that have been observed in such rats treated with angiotensin converting enzyme inhibitor or AT1 receptor antagonist. SN - 0022-2143 UR - https://www.unboundmedicine.com/medline/citation/9104887/Angiotensin_II_receptor_blockade_and_myocardial_fibrosis_of_the_infarcted_rat_heart_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0022-2143(97)90077-9 DB - PRIME DP - Unbound Medicine ER -