Differential remodeling of the left and right heart after norepinephrine treatment in rats: Studies on cytokines and collagen
Differential remodeling of the left and right heart after norepinephrine treatment in rats: Studies on cytokines and collagen
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DOI：
10.1006/jmcc.1999.1075
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发表时间：
2000-02-01
影响因子：
5
通讯作者：
Zimmer, HG
中科院分区：
文献类型：
--
作者：
Barth, W;Deten, A;Zimmer, HG
持续静脉输注去甲肾上腺素（NE, 0.1 mg/kg/h）可引起大鼠左心室（LV）肥厚，但右心室（RV）肥厚不明显，尽管右心室收缩压（RVSP）明显高于左心室（LVSP）。NE输注后，白细胞介素(IL)-6和IL-1 β mRNA表达呈时间依赖性（20 min ~ 72 h）。IL-6的表达明显增加，在4 h后达到最大值，升高80倍。在RV中，表达仅增加了20倍。NE刺激后，IL-1 β mRNA仅在左室显著升高，12 h后达到最高值，升高12倍。NE输注12小时后，胶原蛋白mRNA首次升高，并进一步进展至72小时。72小时后，左室的胶原蛋白mRNA丰度明显高于右室的6倍。蛋白水平也有类似的升高（Western blotting）。仅在左室，24 h后胶原I和III的表达明显增加。72h后，ⅰ型胶原mRNA表达量增加16倍，ⅲ型胶原mRNA表达量增加10倍。这种表达明显高于RV。心房利钠肽（ANP） mRNA的升高在左室比右室开始得更早，且更明显。α和β肾上腺素能受体阻滞剂卡维地洛在6小时和72小时后使所有功能参数正常化，并阻止72小时后发生的左室肥大的发生。通过α和β受体联合阻断，ne诱导的mrna表达增加被阻止（IL-6, IL-1 β）或减弱（胶原蛋白，胶原I和III， ANP）。钙通道阻滞剂尼索地平可使与NE效应相关的后负荷升高正常化，但NE诱导的左室肥大、ANP和胶原mRNA的增加不受影响。(C) 2000年学术出版社。
Continuous intravenous infusion of norepinephrine norepinephrine (NE, 0.1 mg/kg/h) induced hypertrophy of the left ventricle (LV), but not of the right ventricle (RV) in rats, although RV systolic pressure (RVSP) was much more elevated than LVSP. After NE infusion, there was a time-dependent (20 min to 72 h) expression in the mRNA of interleukin (IL)-6 and IL-1 beta. The expression of IL-6 increased markedly and reached the maximum after 4 h with an 80-fold elevation. In the RV, the expression increased only 20-fold. The mRNA of IL-1 beta increased significantly after NE stimulation only in the LV and reached the maximum after 12 h with a 12-fold elevation. After 12 h of NE infusion, colligin mRNA was elevated for the first time with further progression until 72 h. The six-fold abundance of colligin mRNA seen after 72 h was significantly higher in the LV than in the RV. A similar increase was observed on the protein level (Western blotting). The expression of collagen I and III increased significantly after 24 h only in the LV. After 72 h, the mRNA expression of collagen I was increased 16-fold and that of collagen III 10-fold. This expression was significantly higher than that in the RV. Also the elevation in atrial natriuretic peptide (ANP) mRNA started earlier and was more pronounced in the LV than in the RV. The alpha- and beta-adrenergic receptor blocker carvedilol normalized all functional parameters after 6 h and 72 h and prevented the development of LV hypertrophy that occurred after 72 h. The NE-induced increased expression of the mRNAs studied was either prevented (IL-6, IL-1 beta) or attenuated (colligin, collagen I and III, ANP) by combined alpha- and beta-receptor blockade. The elevation of afterload which was associated with the NE effect was normalized by the calcium-channel blocker nisoldipin, but NE-induced LV hypertrophy and the increase in ANP and collagen mRNA were not affected. (C) 2000 Academic Press.