Cardioprotective effects of a selective B 2 receptor agonist of bradykinin post-acute myocardial infarct

Maria Marketou, Ekaterina Kintsurashvili, Kyriakos N. Papanicolaou, Hector A. Lucero, Irene Gavras, Haralambos Gavras

Research output: Contribution to journalArticle

Abstract

The cardioprotective benefits of bradykinin are attributable to activation of its B 2 receptor (B 2 R)-mediated actions and abolished by B 2 R antagonists. The current experiments evaluated the cardioprotective potential of a potent, long-acting B 2 R-selective agonist peptide analogue of bradykinin, the compound NG291.MethodsWe compared the extent of cardiac tissue damage and remodeling and expression pattern of selected genes in mice submitted to acute myocardial infarct (MI) and treated for 1 week with either NG291 Hyp 3,Thi 5, N Chg 7,Thi 8-bradykinin or with saline delivered via osmotic minipump.ResultsActive treatment resulted in better ejection fraction (EF) 69 1% vs. 61 3.1% (P = 0.01), (vs. 85 1.3% in sham-operated controls), fractional shortening (FS) 38 4% vs. 32 8% (NS) (vs. 53 1.2 in sham-operated controls), and fewer markers of myocyte apoptosis (TUNEL-positive nuclei 4.9 1.1% vs. 9.7 0.03%, P = 0.03). Systolic blood pressure (SBP) at end point was normal at 110 4.2 in actively treated mice, but tended to be lower at 104 4.7mmHg in saline controls with decreased cardiac systolic capacity. Expression patterns of selected genes to factors related to tissue injury, inflammation, and metabolism (i.e., the B 1 R, B 2 R, endothelial nitric oxide synthase (eNOS), TNF-α, cardiomyopathy-associated 3 (Cmya3), and pyruvate dehydrogenase kinase isoenzyme 4 (PDK4)) showed that acute MI induced significant upregulation of these genes, and active treatment prevented or attenuated this upregulation, whereas the B 2 R agonist itself produced no difference in the myocardium of sham-operated mice.ConclusionsTreatment with a selective B 2 R agonist initiated at the time of induction of acute MI in mice had a beneficial effect on cardiac function, tissue remodeling, and inflammation-related tissue gene expression, which may explain its structural and functional benefits.

Original languageEnglish (US)
Pages (from-to)562-568
Number of pages7
JournalAmerican Journal of Hypertension
Volume23
Issue number5
DOIs
StatePublished - May 1 2010
Externally publishedYes

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Keywords

  • Blood pressure
  • Bradykinin analogue
  • Cardiac function
  • Cardiac remodeling
  • Hypertension
  • Myocardial ischemia

ASJC Scopus subject areas

  • Internal Medicine

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