—Using B₂ kinin receptor gene knockout mice (B₂^−/−), we tested the hypothesis that (l) lack of B₂ receptors may affect blood pressure and cardiac function and aggravate cardiac remodeling after myocardial infarction (MI), and (2) kinins partially mediate the cardiac beneficial effect of angiotensin-converting enzyme inhibitors (ACEi) or angiotensin II type 1 receptor antagonists (AT₁-ant), whereas lack of B₂ receptors may diminish this cardioprotective effect. Chronic heart failure (HF) was induced by MI, which was caused by coronary artery ligation in both B₂^−/− and 129/SvEvTac mice (wild-type control, B₂^+/+). An ACEi (ramipril, 2.5 mg/kg/d) or AT₁-ant (L-158809, 3 mg/kg/d) was given 1 week after MI and was continued for 12 weeks. Left ventricular (LV) ejection fraction, cardiac output (CO), diastolic LV dimension (LVDd), and LV mass were evaluated by echocardiography. Myocyte cross-sectional area and interstitial collagen fraction were studied histopathologically. We found that basal blood pressure and cardiac function were similar in B₂^+/+ and B₂^−/− mice. After MI, development of HF and remodeling were also similar between the 2 strains. The ACEi improved cardiac function and remodeling in both strains; however, its effects were attenuated in B₂^−/− mice (respective values for B₂^+/+ versus B₂^−/− mice: overall increase in ejection fraction, 64±10% versus 21±5% [P<0.01]; increase in CO, 69±17% versus 23±9% [P<0.01]; overall decrease in LVDd, −24±3% versus −7±4% [P<0.01]; and decrease in LV mass, −38±3% versus −6±6% [P<0.01]). AT₁-ant had a beneficial cardiac effect similar to that produced by ACEi, and this effect was also diminished in B₂^−/− mice (respective values for B₂^+/+ versus B₂^−/− mice: overall increase in ejection fraction, 46±10% versus 25±9% [P<0.01]; increase in CO, 44±14% versus 15±5% [P<0.01]; overall decrease in LVDd, −14±4% versus −6±3% [P<0.01]; and decrease in LV mass, −33±4 versus −16±7% [P<0.01]). The effect of ACEi or AT₁-ant on myocyte cross-sectional area was similar between strains; however, their effect on the interstitial collagen fraction was diminished in B₂^−/− mice. We concluded that (1) lack of B₂ kinin receptors does not affect cardiac phenotype or function, either under normal physiological conditions or during the development of HF; and (2) kinins acting via the B₂ receptor play an important role in the cardioprotective effect of ACEi and AT₁-ant.