Catecholamine metabolism inhibitors and receptor blockades only partially suppress cardiac hypertrophy of juvenile visceral steatosis mice with systemic carnitine deficiency
Catecholamine metabolism inhibitors and receptor blockades only partially suppress cardiac hypertrophy of juvenile visceral steatosis mice with systemic carnitine deficiency
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DOI：
10.1016/s0024-3205(99)00042-9
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发表时间：
1999-02-19
期刊：
影响因子：
6.1
通讯作者：
Saheki, T
中科院分区：
文献类型：
--
作者：
Jalil, MA;Horiuchi, M;Saheki, T
为了阐明肉碱缺乏JVS小鼠心肌肥大的机制，我们研究了儿茶酚胺代谢的可能作用。心肌肥大发生在出生后2周。JVS组小鼠2周时脑室去甲肾上腺素周转率是对照组的3倍，而在心脏重量不变的第5天，去甲肾上腺素周转率与对照组无明显差异。为了评价去甲肾上腺素代谢加速的作用，我们观察了儿茶酚胺代谢抑制剂(cr-甲基酪氨酸和6-羟基多巴胺)和儿茶酚胺受体阻滞剂(心得安、哌唑嗪和育亨宾)对心脏重量/体重(HW/BW)和心房利钠肽(ANP)和下调的心脏肉碱缺乏相关基因(CDV-1)表达的影响。经儿茶酚胺代谢抑制剂和受体阻滞剂治疗的JVS小鼠的HW/BW比值显著低于未治疗的JVS小鼠，但仍高于每种药物治疗的对照组和肉碱治疗的JVS小鼠。心得安治疗的JVS小鼠的HW/BW与经儿茶酚胺代谢抑制剂治疗的JVS小鼠无显著差异，但显著低于经哌唑嗪和育亨宾治疗的JVS小鼠。Northern印迹分析显示，除卡尼汀外，其他药物均不能纠正JVS小鼠脑室ANP和CDV-1表达的改变。上述结果提示，JVS小鼠2周时心肌儿茶酚胺代谢加速不是心肌肥厚的主要原因，但可能主要通过P-肾上腺素能信号通路促进心肌肥厚。在JVS小鼠中发现的ANP和CDV-1基因的异常表达似乎不依赖于儿茶酚胺代谢，主要由全身性肉碱缺乏介导。
To clarify the mechanism of cardiac hypertrophy in carnitine-deficient JVS mice, we studied the possible role of catecholamine metabolism. Cardiac hypertrophy occurs 2 weeks after birth. The turnover of norepinephrine in the ventricles of JVS mice at 2 weeks was 3 times that of control, but it was not different from control at 5 days when the heart weight was not changed. To evaluate the accelerated norepinephrine turnover, we examined the effects of catecholamine metabolism inhibitors (cr-methyltyrosine and 6-hydroxydopamine) and catecholamine receptor blockades (propranolol, prazosin and yohimbine) on the ratio of heart weight to body weight (HW/BW) and on the augmented expression of atrial natriuretic peptide (ANP) and the down-regulated carnitine deficiency-associated gene expressed in ventricle (CDV-1). The HW/BW ratio in JVS mice treated with catecholamine metabolism inhibitors and receptor blockades was significantly lower than in JVS mice without treatment, but still higher than in controls treated with each drug and in JVS mice treated with carnitine. The HW/BW ratio of JVS mice with propranolol was not significantly different from that of JVS mice treated with catecholamine metabolism inhibitors and was significantly lower than that of JVS mice treated with prazosin and yohimbine. Northern blot analysis showed that the altered expression of ANP and CDV-1 was not corrected in the ventricles of JVS mice treated with any of the drugs except carnitine. These results suggest that the catecholamine metabolism accelerated in JVS mice ventricles at 2 weeks is not the major cause of cardiac hypertrophy, but probably promotes cardiac hypertrophy mainly through the P-adrenergic signaling pathway. The aberrant gene expression of ANP and CDV-1 found in JVS mice seems to be independent of catecholamine metabolism, and mediated primarily by the systemic carnitine deficiency.