Zhang Le-Feng, Peng Shuang-Qing, Wang Sheng, Li Bian-Lan, Han Gang, Dong Yan-Sheng
Department of Occupational and Environmental Health, School of Public Health, Peking University Health Science Center, Beijing 100083, PR China.
Toxicol Lett. 2007 Apr 25;170(2):104-10. doi: 10.1016/j.toxlet.2007.02.004. Epub 2007 Feb 20.
Lead (Pb(2+)) exposure is related to increased blood pressure or hypertension of human or animals. Abnormal vascular relaxant responses of low level Pb(2+) exposed animals were reported by several studies. However, it is difficult to tell whether these effects were induced directly by Pb(2+) or not. In this study we hypothesized that Pb(2+) can directly affect the relaxation of vessels. Male Wistar rat aortae were removed and cultured in PMRI 1640 with 1 ppm Pb(2+) (4.8 microM lead acetate) for 0.5, 6, 12 and 24h, and then their responses to acetylcholine (ACh) and sodium nitroprusside (SNP) were examined. After incubated for 24h, the relaxation induced by ACh was significantly decreased in Pb(2+) exposed aortic rings. However, there was not significant difference in relaxation induced by SNP between Pb(2+) exposed and control group. The nitrite in the culture media of aortic rings cultured for 24h, measured with Griess method, was significantly decreased in the Pb(2+) exposed group. The expression of endothelial NOS (eNOS) and isoform NOS (iNOS) in the homogenate of aortic rings cultured for 24h was measured by Western blot. The expression of eNOS of the Pb(2+) exposed group was significantly upregulated compared with that of the control group. However, there was no significant difference in the expression of iNOS in control and Pb(2+) exposed group. In conclusion, Pb(2+) was able to directly affect the relaxation of rat aorta. This effect may have some relation with the lower level of NO in the media, though the expression of eNOS was upregulated.
铅(Pb(2+))暴露与人类或动物的血压升高或高血压有关。多项研究报道了低水平Pb(2+)暴露动物的血管舒张反应异常。然而,很难判断这些效应是否由Pb(2+)直接诱导。在本研究中,我们假设Pb(2+)可直接影响血管舒张。取出雄性Wistar大鼠的主动脉,在含1 ppm Pb(2+)(4.8 microM醋酸铅)的PMRI 1640培养基中培养0.5、6、12和24小时,然后检测其对乙酰胆碱(ACh)和硝普钠(SNP)的反应。培养24小时后,Pb(2+)暴露的主动脉环中ACh诱导的舒张显著降低。然而,Pb(2+)暴露组与对照组之间SNP诱导的舒张无显著差异。用Griess法测定培养24小时的主动脉环培养基中的亚硝酸盐,Pb(2+)暴露组显著降低。通过蛋白质印迹法测定培养24小时的主动脉环匀浆中内皮型一氧化氮合酶(eNOS)和诱导型一氧化氮合酶(iNOS)的表达。与对照组相比,Pb(2+)暴露组的eNOS表达显著上调。然而,对照组和Pb(2+)暴露组的iNOS表达无显著差异。总之,Pb(2+)能够直接影响大鼠主动脉的舒张。尽管eNOS表达上调,但这种效应可能与培养基中较低水平的一氧化氮有关。