title: Prevention of cardiac remodeling after myocardial infarction in transgenic rats deficient in brain angiotensinogen.
abstract: The brain renin-angiotensin-aldosterone system (RAAS) plays a major role in cardiac remodeling after myocardial infarction (MI). To assess the contribution of the brain RAAS in the activation of the cardiac RAAS post-MI, transgenic (TG) rats deficient in brain angiotensinogen and Wistar rats with intracerebroventricular (ICV) infusion of spironolactone were studied. An MI was induced by acute coronary artery ligation. TG and control Sprague-Dawley (SD) rats were followed for 8 weeks and Wistar rats for 6 weeks. Infarct sizes, % of left ventricle (LV) area, were in the 30-33% range. In SD rats at 8 weeks post-MI, internal circumference, interstitial and perivascular fibrosis, cardiomyocyte diameter in the LV and right ventricle (RV), laminin and fibronectin in the LV, and lung weights were increased. Aldosterone was increased markedly in both the LV and RV at 8 weeks post-MI. In TG rats, the MI-induced increases of RV internal circumference and weight were prevented and increases of lung weight and LV internal circumference were significantly inhibited. In TG rats, the post-MI increases of interstitial fibrosis and cardiomyocyte diameter were prevented in septum and RV and significantly inhibited in the peri-infarct zone of the LV. The increases in perivascular fibrosis, laminin and fibronectin were prevented in the LV. In TG rats, cardiac aldosterone did not increase. In Wistar rats at 6 weeks post-MI, aldosterone was markedly increased in the LV, but not in the RV. This increase was prevented by ICV infusion of spironolactone. These findings support the pivotal role of locally produced angiotensin II in the brain in cardiac remodeling post-MI. The brain RAAS appears to activate a cascade of events, among others an increase in cardiac aldosterone, which play a major role in cardiac remodeling post-MI.
authors.affiliation: Hypertension Unit, University of Ottawa Heart Institute, Ont., Canada.
authors.forename: Avtar
authors.initials: A
authors.lastname: Lal
authors.forename: John P
authors.initials: JP
authors.lastname: Veinot
authors.forename: Detlev
authors.initials: D
authors.lastname: Ganten
authors.forename: Frans H H
authors.initials: FH
authors.lastname: Leenen
mesh_terms: D000450:Aldosterone / Q000032:analysis / Q000378:metabolism; D000808:Angiotensinogen / Q000172:deficiency* / Q000235:genetics; D000818:Animals; D030801:Animals, Genetically Modified; D001921:Brain / Q000378:metabolism*; D048429:Cell Size; D005353:Fibronectins / Q000378:metabolism; D005355:Fibrosis / Q000473:pathology; D006352:Heart Ventricles / Q000737:chemistry; D007150:Immunohistochemistry; D007797:Laminin / Q000378:metabolism; D008297:Male; D009203:Myocardial Infarction / Q000209:etiology / Q000378:metabolism / Q000473:pathology* / Q000503:physiopathology*; D032383:Myocytes, Cardiac / Q000473:pathology; D009929:Organ Size; D011863:Radioimmunoassay; D011897:Random Allocation; D051381:Rats / Q000235:genetics; D017207:Rats, Sprague-Dawley; D017208:Rats, Wistar; D013148:Spironolactone / Q000494:pharmacology; D013997:Time Factors; D016277:Ventricular Function, Left; D020257:Ventricular Remodeling
chemical_list: D005353:Fibronectins; D007797:Laminin; D000808:Angiotensinogen; D013148:Spironolactone; D000450:Aldosterone