左旋硝基精氨酸诱导的大鼠高血压主动脉血色素加氧酶mRNA表达及活性改变

Changes of aortic tissue heme oxygenase (HO) activity and HO-1 mRNA expression in hypertensive rats induced by N~ω-niotro-L-arginine

目的 研究血色素加氧酶 (HemeOxyenase ,HO)在左旋硝基精氨酸 (Nω-Nitro -arginine ,L -NNA)诱导的大鼠高血压模型主动脉中的改变及HO底物血色素 -左旋 -赖氨酸 (Heme -L -Lysinate ,HLL)的影响。方法 对Wistar大鼠每日分别给予L -NNA 15mg/kg、L -NNA 15mg/kg并每日加HLL 15mg/kg ,观察大鼠动脉血压 ,主动脉HO活性、HO -1mRNA表达的变化。结果 L -NNA可明显诱导大鼠血压升高 ,在第 4周末 ,与对照组相比 ,血压平均升高 5 9% (P <0 0 5 )。同时加用HLL组血压未见升高。大鼠主动脉HO活性分别增加 31 2 %和 5 5 2 % (与对照组比 ,P <0 0 5 ) ,HO - 1mRNA表达分别增加 31 8%和 148 0 % (均为P <0 0 5 )。同时注射HO底物血色素和L -NNA时 ,主动脉平滑肌HO活性及HO - 1mRNA表达较单纯L -NNA组增加更为明显。结果表明 ,HO/CO通路在L -NNA诱导的大鼠高血压形成过程中可呈代偿性上调状态 ,HO活性的增加是可诱导的HO - 1mRNA表达增加的结果 ,加用HO底物可降低升高的血压。结论 HO/CO通路参与血管张力的调节 ,对L

Objective To investigate the expression and activity of heme oxygenase (HO) in hypertensive rats induced by N ω-nitro-L-arginine (L-NNA),and the effect of hemin-L-lysinate (HLL)(a HO substrate).Methods Fighteen male Wistar rats were randomly divided into three groups:L-NNA group,treated with 15 mg·kg 1 ·d 1 by intraperitoneal injection for four weeks group;L-NNA+HLL group,treated with L-NNA 15 mg·kg 1 ·d 1 and HLL by intraperitoneal injection for four weeks;and control rats at the end of the fourth week,the tail anterial pressures were measured with the RBP-1 pressure measurement.After that,the rats were killed and the aortae were taken out.And then the Northern blot method was used to detect the expression of HO-1 mRNA,the HO activity within aortic smooth muscle tissues were examined.Results After treatment with L-NNA for four weeks,the mean blood pressure increased 59% more than that of the control group (P<0.05).HLL could reduce the blood pressure significantly.HO-1 mRNA expression and HO activity were detected in all aortae,and particularly abundant in L-NNA group and L-NNA+HLL group,the HO activity and expression of HO-1 mRNA from arotic tissue in L-NNA+HLL group (55.2% and 148%)were more enhanced than that in single L-NNA treated rats (31.2% and 31.8%) (vs control and L-NNA group,P<0.05).The data revealed that endogenous HO/CO system was upregulated and reduced the blood pressure.Conclusion In the aortae of rats with hypertension on induced by L-NNA,the HO-1 expression and activity increase,and will increased more by treatment with HLL.The HO/CO system can be compensated partly for regulating the pathogenesis of hypertension induced by NO synthase inhibition.