title: Differential effects of kinins on cardiomyocyte hypertrophy and interstitial collagen matrix in the surviving myocardium after myocardial infarction in the rat.
abstract: BACKGROUND
  Left ventricular remodeling after myocardial infarction (MI) involves the hypertrophic growth of cardiomyocytes and the accumulation of fibrillar collagen in the interstitial space. We evaluated the role of kinins in postinfarction ventricular remodeling and their potential contribution to the antiremodeling effects of ACE inhibition and angiotensin II type 1 (AT1) receptor blockade.
  
  
  RESULTS
  Rats underwent coronary artery ligation followed by chronic B2 kinin receptor blockade with icatibant. Additional groups of infarcted rats were treated with the ACE inhibitor lisinopril or the AT1 receptor antagonist ZD7155, each separately and in combination with icatibant. B2 kinin receptor blockade enhanced the interstitial deposition of collagen after MI, whereas morphological and molecular markers of cardiomyocyte hypertrophy (cardiac weight, myocyte cross-sectional area, prepro-atrial natriuretic factor mRNA expression) were not affected. Chronic ACE inhibition and AT1 receptor blockade reduced collagen deposition and cardiomyocyte hypertrophy after MI. The inhibitory action of ACE inhibition and AT1 receptor blockade on interstitial collagen was partially reversed by B2 kinin receptor blockade. However, B2 kinin receptor blockade did not attenuate the effects of ACE inhibition and AT1 receptor blockade on cardiomyocyte hypertrophy.
  
  
  CONCLUSIONS
  (1) Kinins inhibit the interstitial accumulation of collagen but do not modulate cardiomyocyte hypertrophy after MI. (2) Kinins contribute to the reduction of myocardial collagen accumulation by ACE inhibition and AT1 receptor blockade. (3) The effects of ACE inhibition and AT1 receptor blockade on cardiomyocyte hypertrophy are related to a reduced generation/receptor blockade of angiotensin II.
authors.affiliation: Medizinische Klinik III, Arbeitsgruppe Molekulare Kardiologie, Universität Freiburg, Germany.
authors.forename: K C
authors.initials: KC
authors.lastname: Wollert
authors.forename: R
authors.initials: R
authors.lastname: Studer
authors.forename: K
authors.initials: K
authors.lastname: Doerfer
authors.forename: E
authors.initials: E
authors.lastname: Schieffer
authors.forename: C
authors.initials: C
authors.lastname: Holubarsch
authors.forename: H
authors.initials: H
authors.lastname: Just
authors.forename: H
authors.initials: H
authors.lastname: Drexler
mesh_terms: D000319:Adrenergic beta-Antagonists / Q000494:pharmacology*; D057911:Angiotensin Receptor Antagonists; D000806:Angiotensin-Converting Enzyme Inhibitors / Q000494:pharmacology*; D000818:Animals; D009320:Atrial Natriuretic Factor / Q000096:biosynthesis / Q000235:genetics; D001920:Bradykinin / Q000031:analogs & derivatives* / Q000187:drug effects / Q000494:pharmacology; D065168:Bradykinin Receptor Antagonists; D003094:Collagen / Q000032:analysis*; D004790:Enzyme Induction / Q000187:drug effects; D005109:Extracellular Matrix / Q000187:drug effects* / Q000473:pathology; D005786:Gene Expression Regulation / Q000187:drug effects; D006352:Heart Ventricles / Q000187:drug effects / Q000473:pathology; D006439:Hemodynamics / Q000187:drug effects; D006984:Hypertrophy; D007705:Kinins / Q000502:physiology*; D008297:Male; D009200:Myocardial Contraction / Q000187:drug effects; D009203:Myocardial Infarction / Q000473:pathology*; D009206:Myocardium / Q000378:metabolism / Q000473:pathology*; D009287:Naphthyridines / Q000494:pharmacology*; D019001:Nitric Oxide Synthase / Q000096:biosynthesis / Q000235:genetics; D007703:Peptidyl-Dipeptidase A / Q000032:analysis; D016133:Polymerase Chain Reaction; D051381:Rats; D017207:Rats, Sprague-Dawley; D043782:Receptor, Bradykinin B2; D016037:Single-Blind Method
chemical_list: D000319:Adrenergic beta-Antagonists; D057911:Angiotensin Receptor Antagonists; D000806:Angiotensin-Converting Enzyme Inhibitors; D065168:Bradykinin Receptor Antagonists; D007705:Kinins; D009287:Naphthyridines; D043782:Receptor, Bradykinin B2; C095905:ZD 7155; C065679:icatibant; D009320:Atrial Natriuretic Factor; D003094:Collagen; D019001:Nitric Oxide Synthase; D007703:Peptidyl-Dipeptidase A; D001920:Bradykinin