ANGIOTENSIN RECEPTOR REGULATES CARDIAC-HYPERTROPHY AND TRANSFORMING GROWTH FACTOR-BETA(1) EXPRESSION
ANGIOTENSIN RECEPTOR REGULATES CARDIAC-HYPERTROPHY AND TRANSFORMING GROWTH FACTOR-BETA(1) EXPRESSION
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DOI：
10.1161/01.hyp.23.5.587
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发表时间：
1994-05-01
期刊：
影响因子：
8.3
通讯作者：
GOMEZ, RA
中科院分区：
文献类型：
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作者：
EVERETT, AD;TUFROMCREDDIE, A;GOMEZ, RA
在腹主动脉缩窄的成年雄性Sprague-Dawley大鼠中测定血管紧张素II通过血管紧张素1型或2型受体在心脏肥大发展中的作用。研究了五组动物：缩窄、缩窄加DuP 753、缩窄加PD 123319、假手术加DuP 753或假手术。从手术当天开始，直至主动脉缩窄后72小时，通过饮用水给予DuP 753实现1型受体阻滞，通过渗透微泵给予PD 123319实现2型受体阻滞。缩窄、缩窄+DuP 753和缩窄+PD 123319动物之间的平均颈动脉血压和颈动脉-股动脉血压梯度无差异。然而，缩窄组（4.95 +/- 0.8）或缩窄加PD 123319组（4.52 +/- 0.5）的心脏重量/体重比高于假手术组（3.6 +/- 0.4; P分别<0.005和0.05）。在缩窄加DuP 753给药动物中，心脏重量-体重比与假手术或假手术加DuP 753动物无差异（分别为3.9 +/- 0.4 vs 3.61 +/- 0.4或3.3 +/- 0.08）。1型受体mRNA水平在缩窄组中显著增加，其中在缩窄加DuP 753和假手术加DuP 753组中水平最高。为了确定生长因子是否参与了肥大过程，我们测量了转化生长因子β 1 mRNA水平。北方分析表明，与假手术或缩窄加DuP 753治疗的动物相比，缩窄动物增加了两倍。因此，腹主动脉缩窄诱导的心脏肥大由血管紧张素1型受体介导，并导致心脏血管紧张素1型和转化生长因子β（1）基因上调。
The role of angiotensin II via the angiotensin type 1 or type 2 receptor in the development of cardiac hypertrophy was determined in adult male Sprague-Dawley rats subjected to coarctation of the abdominal aorta. Five groups of animals were studied: coarctation, coarctation plus DuP 753, coarctation plus PD 123319, sham plus DuP 753, or sham operation. Type 1 receptor blockade was accomplished with DuP 753 given in the drinking water and type 2 blockade with PD 123319 delivered by osmotic minipumps beginning with the day of surgery until 72 hours after aortic coarctation. Mean carotid blood pressures and the carotid-femoral artery blood pressure gradients were not different among coarctation, coarctation plus DuP 753, and coarctation plus PD 123319 animals. However, ratios of heart weight to body weight were higher in coarctation (4.95 +/- 0.8) or coarctation plus PD 123319 (4.52 +/- 0.5) than in sham animals (3.6 +/- 0.4; P < .005 and .05, respectively). In coarctation plus DuP 753-treated animals heart weight-body weight ratios were not different from sham or sham plus DuP 753 animals (3.9 +/- 0.4 versus 3.61 +/- 0.4 or 3.3 +/- 0.08, respectively). Type 1 receptor mRNA levels were significantly increased in the coarctation group, with the highest levels in the coarctation plus DuP 753 and sham plus DuP 753 groups. To determine whether growth factors were involved in the hypertrophic process, we measured transforming growth factor-beta(1) mRNA levels. Northern analysis demonstrated a twofold increase in coarctation animals compared with sham or coarctation plus DuP 753-treated animals. Therefore, cardiac hypertrophy induced by abdominal coarctation of the aorta is mediated by the angiotensin type 1 receptor and results in upregulation of the cardiac angiotensin type 1 and transforming growth factor-beta(1) genes.