Role of the B1 kinin receptor in the regulation of cardiac function and remodeling after myocardial infarction.
Kinins exert cardioprotective effects via 2 G-protein-coupled receptors, B1 and B2. Using B1 kinin receptor gene knockout mice (B1-/-), we tested the hypotheses that the B1 receptor plays an important role in preservation of cardiac function, whereas lack of B1 may accelerate cardiac remodeling and dysfunction after myocardial infarction, and that B2 receptors may compensate for lack of B1, whereas blockade of B2 receptors in B1-/- mice may cause further deterioration of cardiac function and remodeling. Female B1-/- mice and wild-type controls (C57BL/6J, B1+/+) underwent sham surgery or myocardial infarction and were treated with either vehicle or B2-antagonist (icatibant, 500 microg/kg per day, subcutaneous) for 8 weeks. We found that in sham myocardial infarction, B1-/- mice had a larger left ventricular diastolic chamber dimension both initially and at 4 to 8 weeks compared with B1+/+. Left ventricular mass and myocyte size were also larger in B1-/- with sham operation than in B1+/+, although cardiac function did not differ between strains. After myocardial infarction, cardiac remodeling and function were similar in both strains, although B1-/- mice tended to have lower blood pressure. Blockade of B2 receptors tended to worsen cardiac remodeling and dysfunction in B1-/- but not in B1+/+. These results may suggest that B2 receptors play an important role in compensating for lack of B1 receptors in mice with myocardial infarction. Dual blockade of both B1 and B2 eliminates this compensation, leading to further deterioration of cardiac dysfunction and remodeling after myocardial infarction.
Xu
Jiang
J
Hypertension and Vascular Research Division, Henry Ford Hospital, Detroit, Mich 48202-2689, USA.
Carretero
Oscar A
OA
Sun
Ying
Y
Shesely
Edward G
EG
Rhaleb
Nour-Eddine
NE
Liu
Yun-He
YH
Liao
Tang-Dong
TD
Yang
James J
JJ
Bader
Michael
M
Yang
Xiao-Ping
XP
D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D001920:Bradykinin / Q000494:pharmacology; D065094:Bradykinin B2 Receptor Antagonists; D005260:Female; D006321:Heart / Q000503:physiopathology*; D006339:Heart Rate; D006352:Heart Ventricles; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009203:Myocardial Infarction / Q000401:mortality / Q000473:pathology / Q000503:physiopathology*; D009206:Myocardium / Q000378:metabolism* / Q000473:pathology; D009929:Organ Size; D043783:Receptor, Bradykinin B1 / Q000172:deficiency / Q000378:metabolism*; D013599:Systole; D020257:Ventricular Remodeling
D065094:Bradykinin B2 Receptor Antagonists; D043783:Receptor, Bradykinin B1; D001920:Bradykinin