Abstract 1702: Blockade of B1 in Kinin B2 Receptor knockout mice Deteriorates Cardiac Function and Remodeling post-Myocardial Infarction
We previously showed that the therapeutic effects of ACEi were diminished in B2 knockout mice (B2−/−). However, lack of B2 per se did not affect cardiac remodeling and dysfunction post myocardial infarction (MI), which may be partially due to upregulation of B1 that may play a compensatory role for lack of the B2. Here we hypothesize that blockade of B1 in B2−/− mice accelerates and deteriorates cardiac remodeling and dysfunction post-MI. Male B2−/− and wild-type controls (C57BL/6J, B2+/+) were subjected to sham MI or MI (by ligating the left anterior descending coronary artery) and treated with either vehicle or B1 antagonist (B1-ant, Ac-Lys[(αMe)phe5,D-βNal7,Ile8]desArg9BK; 300 μg/kg/day via osmotic minipump, i.p.) for 8 weeks. Systolic blood pressure (SBP) was measured weekly by tail cuff, and LV diastolic chamber dimension (LVDd), mass and ejection fraction (EF) were evaluated by echocardiography. We found that SBP, cardiac morphology and function did not differ between strains in sham-MI mice. MI caused a similar increase in LV chamber dilatation and mass and decrease in EF between B2+/+ and B2−/− (Table⇓). However, in the presence of B1-ant, cardiac remodeling and dysfunction post-MI became more severe in B2−/− mice compared to B2+/+. SBP and infarct size were similar in all groups. These results suggest that the B1 receptor may play an important role in preventing deterioration of cardiac function and remodeling post-MI when B2 receptors are absent.