Expression and localization of angiotensin subtype receptor proteins in the hypertensive rat heart
Expression and localization of angiotensin subtype receptor proteins in the hypertensive rat heart
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DOI：
10.1152/ajpregu.2000.278.3.r781
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发表时间：
2000-03-01
影响因子：
2.8
通讯作者：
Carey, RM
中科院分区：
文献类型：
--
作者：
Ozono, R;Matsumoto, T;Carey, RM
AT（2）受体在肥厚左心室的细胞定位及其表达的调控尚不清楚。我们用免疫组织化学和蛋白质印迹法比较了4、12和20周龄自发性高血压大鼠/Izumo品系（SHR/Izm）和Wistar京都大鼠/Izumo品系（WKY/Izm）心脏AT（1）和AT（2）受体的表达。SHR/Izm组与WKY/Izm组相比，（12周时为161 +/- 2与120 +/- 2 mmHg，P小于或等于0.01，20周时为199 +/- 3与123 +/- 3 mmHg，P ≤ 0.01）和心体重比（12周时3.76 +/- 0.07 vs. 3.06 +/- 0.06 mg/g，P小于或等于0.01，20周时3.90 +/- 0.08 vs. 3.01 +/- 0.12 mg/g，P小于或等于0.01）显著升高。在4周龄时，两个品系之间的这些值没有差异。在组织学上，20周龄SHR/Izm表现出心肌肥大，心内动脉平滑肌层增厚和血管周围纤维化。免疫组化显示AT（2）受体定位于心肌细胞和血管内皮细胞，而不在血管平滑肌细胞。在任何年龄的大鼠血管周围纤维化中均未观察到主要的AT（2）受体信号。两种菌株在此定位上没有差异。通过Western印迹，在所有年龄的两种品系大鼠的心室中检测到AT 2受体的单一44 kDa条带和AT（1）受体的单一60 kDa条带。光密度分析表明，SHR/Izm与WKY/Izm相比，AT（2）受体44 kDa条带在12 wk和20 wk时分别减少20%和32%（P < 0.01）。20周龄SHR/Izm的AT（1）受体60 kDa条带强度较WKY/Izm增加57%（P < 0.05）。有没有显着差异的强度的44或60 kDa的条带在4周龄的动物的任一菌株。我们证明了在SHR/Izm的肥厚左心室肌细胞中AT（2）受体蛋白减少和AT（1）受体蛋白增加，而它们的定位没有变化。
The cellular localization of the AT(2) receptor and the regulation of its expression in hypertrophied left ventricle are not well known. We compared the expression of the cardiac AT(1) and AT(2) receptor in spontaneously hypertensive rats/Izumo strain (SHR/Izm) and Wistar Kyoto rats/Izumo strain (WKY/Izm), ages 4, 12, and 20 wk, by means of immunohistochemistry and Western blot analysis. In SHR/Izm, compared with WKY/Izm, blood pressure (161 +/- 2 vs. 120 +/- 2 mmHg at 12 wk, P less than or equal to 0.01, and 199 +/- 3 vs. 123 +/- 3 mmHg at 20 wk, P less than or equal to 0.01) and heart-to-body weight ratio (3.76 +/- 0.07 vs. 3.06 +/- 0.06 mg/g at 12 wk, P less than or equal to 0.01, and 3.90 +/- 0.08 vs. 3.01 +/- 0.12 mg/g at 20 wk, P less than or equal to 0.01) were significantly elevated. There was no difference in these values between the two strains at 4 wk of age. Histologically, 20-wk-old SHR/Izm demonstrated myocardial hypertrophy, a thickening of the smooth muscle layer of the intracardiac arteries, and perivascular fibrosis. By immunohistochemistry, the AT(2) receptor was localized to cardiomyocytes and vascular endothelial cells, but not in the vascular smooth muscle cells. No major AT(2) receptor signal was observed in perivascular fibrosis at any age in either strain of rats. No difference was detected in this localization between the two strains. By Western blotting, a single 44-kDa band for the AT2 receptor and a single 60-kDa band for the AT(1) receptor were detected in ventricles from both strains of rats at all ages. Densitometric analysis demonstrated that the AT(2) receptor 44-kDa band was decreased by 20% at 12 wk and 32% at 20 wk (P < 0.01) in SHR/Izm compared with WKY/Izm. The intensity of the AT(1) receptor 60-kDa band was increased by 57% in 20-wk-old SHR/Izm compared with WKY/Izm (P < 0.05). There was no significant difference in the intensity of the 44- or 60-kDa bands in 4-wk-old animals of either strain. We demonstrated a decrease in the AT(2) receptor and an increase in the AT(1) receptor protein with no change in their localizations in hypertrophied left ventricular myocytes of SHR/Izm.