Ishizaka N, de León H, Laursen J B, Fukui T, Wilcox J N, De Keulenaer G, Griendling K K, Alexander R W
Department of Medicine, Emory University School of Medicine, Atlanta, Ga 30322, USA.
Circulation. 1997 Sep 16;96(6):1923-9. doi: 10.1161/01.cir.96.6.1923.
We investigated the in vivo effects of angiotensin (Ang) II-induced hypertension on heme oxygenase (HO) mRNA and protein expression, activity, and localization in rat aortas.
Infusion of Ang II (0.7 mg x kg(-1) x d(-1)) increased HO-1 mRNA levels to 169+/-31%, 251+/-47%, 339+/-26%, and 370+/-74% of the control level at 1, 3, 5, and 7 days after operation, respectively. The HO-1 protein level at 7 days was markedly upregulated, as was HO activity. Treatment with either losartan (25 mg x kg(-1) x d(-1)) or hydralazine (15 mg x kg(-1) x d(-1)), both of which prevented the Ang II-induced hypertension, blocked HO-1 mRNA upregulation. Norepinephrine infusion (2.8 mg x kg(-1) x d(-1)) produced a degree of hypertension and degree of HO-1 mRNA upregulation similar to those of Ang II infusion, which was again blocked by treatment with hydralazine (382+/-18% and 150+/-30% of the control level, respectively). Immunohistochemical analysis demonstrated that HO-1 is expressed in medial smooth muscle and adventitial cells in normotensive rat aortas, and this is markedly increased in adventitial and endothelial cells in Ang II-induced hypertensive rat aortas. In contrast, HO-2 protein expression was not changed in hypertensive rat aortas.
These findings indicate that HO-1 is upregulated in hypertensive rat aortas, apparently by mechanisms unique to Ang II and by hemodynamic stress.
我们研究了血管紧张素（Ang）II诱导的高血压对大鼠主动脉中血红素加氧酶（HO）mRNA和蛋白表达、活性及定位的体内影响。
输注Ang II（0.7 mg·kg⁻¹·d⁻¹）使术后1、3、5和7天的HO-1 mRNA水平分别升至对照水平的169±31%、251±47%、339±26%和370±74%。7天时HO-1蛋白水平显著上调，HO活性也是如此。用氯沙坦（25 mg·kg⁻¹·d⁻¹）或肼屈嗪（15 mg·kg⁻¹·d⁻¹）治疗，二者均可预防Ang II诱导的高血压，同时阻断HO-1 mRNA上调。输注去甲肾上腺素（2.8 mg·kg⁻¹·d⁻¹）产生的高血压程度和HO-1 mRNA上调程度与输注Ang II相似，同样可被肼屈嗪治疗阻断（分别为对照水平的382±18%和150±30%）。免疫组织化学分析表明，HO-1在正常血压大鼠主动脉的中层平滑肌和外膜细胞中表达，在Ang II诱导的高血压大鼠主动脉的外膜和内皮细胞中显著增加。相比之下，HO-2蛋白表达在高血压大鼠主动脉中未发生变化。
这些发现表明，HO-1在高血压大鼠主动脉中上调，显然是通过Ang II特有的机制和血流动力学应激实现的。
