TY - JOUR
T1 - Cardioprotective effects of a selective B 2 receptor agonist of bradykinin post-acute myocardial infarct
AU - Marketou, Maria
AU - Kintsurashvili, Ekaterina
AU - Papanicolaou, Kyriakos N.
AU - Lucero, Hector A.
AU - Gavras, Irene
AU - Gavras, Haralambos
N1 - Funding Information:
acknowledgments: We thank Fernand Gobeil from Sherbrooke University, Sherbrooke, Quebec, Canada, for kindly providing us with the bradykinin analogue used in these studies.We also thank Gregory Chlouverakis, associate Professor in the Department of Biostatistics, University of Crete School of Medicine, Greece, for his assistance.This work was supported in part by NIH grant R01 HL58807. M.M. received a scholarship from the Hellenic Cardiological Society.
PY - 2010/5
Y1 - 2010/5
N2 - 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.
AB - 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.
KW - Blood pressure
KW - Bradykinin analogue
KW - Cardiac function
KW - Cardiac remodeling
KW - Hypertension
KW - Myocardial ischemia
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U2 - 10.1038/ajh.2010.20
DO - 10.1038/ajh.2010.20
M3 - Article
C2 - 20186129
AN - SCOPUS:77951136034
SN - 0895-7061
VL - 23
SP - 562
EP - 568
JO - American Journal of Hypertension
JF - American Journal of Hypertension
IS - 5
ER -