Published Online
on February 7, 2005

A more recent version of this article appeared on April 1, 2005

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Submitted on October 8, 2004
Revised on November 10, 2004

Role of the B₁ Kinin Receptor in the Regulation of Cardiac Function and Remodeling After Myocardial Infarction

Jiang Xu; Oscar A. Carretero; Ying Sun; Edward G. Shesely; Nour-Eddine Rhaleb; Yun-He Liu; Tang-Dong Liao; James J. Yang; Michael Bader; and Xiao-Ping Yang^*

From the Hypertension and Vascular Research Division (J.X., O.A.C., Y.S., E.G.S., N.-E.R., Y.-H.L., T.-D.L., X.-P.Y.), Department of Internal Medicine, Department of Biostatistics and Research Epidemiology (J.J.Y.), Henry Ford Hospital, Detroit, Mich; and the Max-Delbrück Center for Molecular Medicine (M.B.), Berlin-Buch, Germany.

^* To whom correspondence should be addressed. E-mail: xpyang1{at}hfhs.org.

Abstract--Kinins exert cardioprotective effects via 2 G-protein-coupled receptors, B₁ and B_2. 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 µg/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.

Key words: kinins • myocardial infarction • mice

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