Wolkowicz P E, Urthaler F, Forrest C, Shen H, Durand J, Wei C C, Oparil S, Dell'Italia L J
The Center for NMR Research and Development, University of Alabama at Birmingham, Birmingham, Alabama, 35294, USA.
J Mol Cell Cardiol. 1999 Aug;31(8):1405-12. doi: 10.1006/jmcc.1999.0977.
Activation of the antiogensin II, type 1 (AT1) receptor mediates the myocardial response to numerous hypertrophic stimuli. This study tested the hypothesis that 2-tetradecylglycidic acid (TDGA), an oxirane carboxylate inhibitor of mitochondrial carnitine plamitoyltransferase-1, induces myocardial hypertrophy via the AT1 receptor system. Male Sprague-Dawley rats treated with 10 mg TDGA/kg/day for 7 days had a heart wet weight:body weight ratio of 3. 58+/-0.16 mg/g compared with a ratio of 2.79+/-0.07 for rats treated with vehicle (P<0.05). The plasma level of antiogensin II was 117. 75+/-17.39 pg/ml in rats treated with 10 mg TDGA/kg/day compared with 54.0+/-11.38 pg/ml for rats treated with vehicle (P<0.05). The plasma level of angiotensin I in these two groups of rats was not different statistically. Rats treated with TDGA and given drinking water containing 1 mg losartan/ml had a heart wet weight:body weight ratio of 2.84+/-0.05 mg/g. This value was not statistically different from the value measured in rats given drinking water containing 1 mg losartan/ml and treated with vehicle alone. No significant difference in the heart wet weight:dry weight ratio occurred among these groups of rats. Finally, treating rats with TDGA or giving rats drinking water that contained 1 mg losartan/ml altered neither their heart rate nor their mean arterial blood pressure when compared with untreated rats. This data, therefore, suggests that oxirane carboxylates induce myocardial hypertrophy by activating the AT1 receptor independent of changes in systemic hemodynamics.
血管紧张素II 1型（AT1）受体的激活介导了心肌对多种肥大刺激的反应。本研究检验了以下假设：2-十四烷基缩水甘油酸（TDGA），一种线粒体肉碱棕榈酰转移酶-1的环氧乙烷羧酸盐抑制剂，通过AT1受体系统诱导心肌肥大。用10mg TDGA/kg/天处理7天的雄性Sprague-Dawley大鼠的心脏湿重与体重之比为3.58±0.16mg/g，而用赋形剂处理的大鼠该比值为2.79±0.07（P<0.05）。用10mg TDGA/kg/天处理的大鼠血浆血管紧张素II水平为117.75±17.39pg/ml，而用赋形剂处理的大鼠为54.0±11.38pg/ml（P<0.05）。这两组大鼠的血浆血管紧张素I水平在统计学上没有差异。用TDGA处理并给予含1mg氯沙坦/ml饮用水的大鼠心脏湿重与体重之比为2.84±0.05mg/g。该值与给予含1mg氯沙坦/ml饮用水并仅用赋形剂处理的大鼠所测得的值在统计学上没有差异。这些组别的大鼠心脏湿重与干重之比没有显著差异。最后，与未处理的大鼠相比，用TDGA处理大鼠或给予含1mg氯沙坦/ml饮用水的大鼠，其心率和平均动脉血压均未改变。因此，这些数据表明环氧乙烷羧酸盐通过激活AT1受体诱导心肌肥大，而与全身血流动力学变化无关。
