Abstract 1702: Blockade of B 1 in Kinin B 2 Receptor knockout mice Deteriorates Cardiac Function and Remodeling post-Myocardial Infarction

Abstract

We previously showed that the therapeutic effects of ACEi were diminished in B 2 knockout mice (B 2 −/−). However, lack of B 2 per se did not affect cardiac remodeling and dysfunction post myocardial infarction (MI), which may be partially due to upregulation of B 1 that may play a compensatory role for lack of the B 2. Here we hypothesize that blockade of B 1 in B 2 −/− mice accelerates and deteriorates cardiac remodeling and dysfunction post-MI. Male B 2 −/− and wild-type controls (C57BL/6J, B 2 +/+) were subjected to sham MI or MI (by ligating the left anterior descending coronary artery) and treated with either vehicle or B 1 antagonist (B 1 -ant, Ac-Lys[(αMe)phe 5 ,D-βNal 7 ,Ile 8 ]desArg 9 BK; 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 B 2 +/+ and B 2 −/− (Table ). However, in the presence of B 1 -ant, cardiac remodeling and dysfunction post-MI became more severe in B 2 −/− mice compared to B 2 +/+. SBP and infarct size were similar in all groups. These results suggest that the B 1 receptor may play an important role in preventing deterioration of cardiac function and remodeling post-MI when B 2 receptors are absent.