Koch Matthias, Bonaventura Klaus, Spillmann Frank, Dendorfer Andreas, Schultheiss Heinz-Peter, Tschöpe Carsten
Department of Cardiology and Pneumology, Charité-University Medicine Berlin, Campus Benjamin Franklin, Hindenburgdamm 30, D-12200 Berlin, Germany.
Biol Chem. 2008 Jun;389(6):719-23. doi: 10.1515/BC.2008.083.
Bradykinin (BK) coronary outflow and left ventricular (LV) performance of kininogen-deficient Brown Norway Katholiek (BNK) rats and Brown Norway Hannover (BNH) controls were investigated. We analyzed whether the angiotensin-converting enzyme (ACE) inhibitor ramipril is able to attenuate LV dysfunction after induction of myocardial infarction (MI) in this animal model. Ex vivo, the basal BK content in the coronary outflow of buffer-perfused, isolated hearts was measured by specific radioimmunoassay. In vivo, left ventricular pressure (LVP), the maximal rate of LVP increase, LV end-diastolic pressure, the maximal rate of LVP decrease and heart rate were determined using a tip catheter 3 weeks after induction of MI. Compared to BNK rats, basal BK outflow was increased 30-fold in controls (p<0.01). In vivo, we found no significant differences between sham-ligated BNK and BNH rats in basal LV function. After MI, the impairment of LV function was significantly worse in BNK rats when compared to BNH rats. ACE inhibition significantly attenuated this LV dysfunction in both groups, when compared to untreated animals. Reduced basal BK level resulting from kininogen deficiency has no effect on basal LV function, but remains to be a risk factor for the ischemic heart. However, ACE inhibition is sufficient to improve LV function despite kininogen deficiency.
研究了激肽原缺乏的褐家鼠（BNK）和褐家鼠汉诺威品系（BNH）对照的缓激肽（BK）冠脉流出量及左心室（LV）功能。我们分析了血管紧张素转换酶（ACE）抑制剂雷米普利是否能够减轻该动物模型中心肌梗死（MI）诱导后的左心室功能障碍。在体外，通过特异性放射免疫测定法测量缓冲液灌注的离体心脏冠脉流出液中的基础BK含量。在体内，在MI诱导3周后，使用顶端导管测定左心室压力（LVP）、LVP最大上升速率、左心室舒张末期压力、LVP最大下降速率和心率。与BNK大鼠相比，对照组的基础BK流出量增加了30倍（p<0.01）。在体内，我们发现假结扎的BNK大鼠和BNH大鼠在基础左心室功能方面没有显著差异。MI后，与BNH大鼠相比，BNK大鼠的左心室功能损害明显更严重。与未治疗的动物相比，ACE抑制在两组中均显著减轻了这种左心室功能障碍。激肽原缺乏导致的基础BK水平降低对基础左心室功能没有影响，但仍是缺血性心脏病的一个危险因素。然而，尽管存在激肽原缺乏，ACE抑制仍足以改善左心室功能。
