title: Effects of a novel bradykinin B1 receptor antagonist and angiotensin II receptor blockade on experimental myocardial infarction in rats.
abstract: BACKGROUND
  The aim of the present study was to evaluate the cardiovascular effects of the novel bradykinin B1 receptor antagonist BI-113823 following myocardial infarction (MI) and to determine whether B1 receptor blockade alters the cardiovascular effects of an angiotensin II type 1 (AT1) receptor antagonist after MI in rats.
  
  
  RESULTS
  Sprague Dawley rats were subjected to permanent occlusion of the left descending coronary artery. Cardiovascular function was determined at 7 days post MI. Treatment with either B1 receptor antagonist (BI-113823) or AT1 receptor antagonist (irbesartan) alone or in combination improved post-MI cardiac function as evidenced by attenuation of elevated left ventricular end diastolic pressure (LVEDP); greater first derivative of left ventricular pressure (± dp/dt max), left ventricle ejection fraction, fractional shorting, and better wall motion; as we as reductions in post-MI up-regulation of matrix metalloproteinases 2 (MMP-2) and collagen III. In addition, the cardiac up-regulation of B1 receptor and AT1 receptor mRNA were markedly reduced in animals treated with BI 113823, although bradykinin B2 receptor and angiotensin 1 converting enzyme (ACE1) mRNA expression were not significantly affected by B1 receptor blockade.
  
  
  CONCLUSIONS
  The present study demonstrates that treatment with the novel B1 receptor antagonist, BI-113823 improves post-MI cardiac function and does not influence the cardiovascular effects of AT1 receptor antagonist following MI.
authors.affiliation: Department of Research, Mount Sinai Medical Center, Miami Beach, Florida, United States of America.
authors.forename: Dongmei
authors.initials: D
authors.lastname: Wu
authors.forename: Xinchun
authors.initials: X
authors.lastname: Lin
authors.forename: Christian
authors.initials: C
authors.lastname: Bernloehr
authors.forename: Tobias
authors.initials: T
authors.lastname: Hildebrandt
authors.forename: Henri
authors.initials: H
authors.lastname: Doods
mesh_terms: D000704:Analysis of Variance; D057911:Angiotensin Receptor Antagonists / Q000494:pharmacology*; D000818:Animals; D001713:Biphenyl Compounds; D001794:Blood Pressure; D015153:Blotting, Western; D065169:Bradykinin B1 Receptor Antagonists; D024061:Collagen Type III / Q000378:metabolism; D017931:DNA Primers / Q000235:genetics; D004452:Echocardiography; D000077405:Irbesartan; D020778:Matrix Metalloproteinase 2 / Q000378:metabolism; D009203:Myocardial Infarction / Q000188:drug therapy / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D043783:Receptor, Bradykinin B1 / Q000378:metabolism; D011945:Receptors, Angiotensin / Q000378:metabolism*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013777:Tetrazoles
chemical_list: D057911:Angiotensin Receptor Antagonists; D001713:Biphenyl Compounds; D065169:Bradykinin B1 Receptor Antagonists; D024061:Collagen Type III; D017931:DNA Primers; D043783:Receptor, Bradykinin B1; D011945:Receptors, Angiotensin; D013777:Tetrazoles; D020778:Matrix Metalloproteinase 2; D000077405:Irbesartan