Gökalp O, Ozdem S, Dönmez S, Dogan M, Demirin H, Kara H Y, Sütcü R, Cicek E, Ozer M K, Delibas N
Department of Pharmacology, School of Medicine, Dicle University, Diyarbakir, Turkey.
Toxicol Ind Health. 2009 Aug;25(7):447-53. doi: 10.1177/0748233709106822. Epub 2009 Jul 31.
Abnormalities in the production and/or release of relaxing factors from the endothelium have been implicated in the development of hypertension in several animal models. Endothelium-dependent relaxation has been reported to be impaired in thoracic aorta in experimentally induced and genetically hypertensive rats. Present study has extented these observations to thoracic aorta of cadmium-hypertensive rats. The possible role of alterations in oxidant status was also studied. Hypertension was induced by the intraperitoneal administration of 1 mg/kg/day cadmium for 15 days. Mechanical responses produced by acetylcholine (ACh, 10(-9)-10(-4) M) and sodium nitroprusside (SNP, 10(-10)-10(-5) M) were studied on phenylephrine-precontracted thoracic aorta rings from control and cadmium-hypertensive rats. Serum nitric oxide (NO) and aortic malondialdehyde (MDA) levels were measured. ACh-induced relaxation was attenuated in aorta from cadmium-hypertensive rats, whereas relaxation responses to SNP did not differ significantly between the groups. Exposure of aortic rings to N(G)-nitro-L-arginine methyl ester (L-NAME, 10(-4) M) resulted in a significantly greater inhibition of relaxation response to ACh in aortic rings of cadmium-hypertensive rats as compared with control rats. Incubation with L-arginine (L-Arg, 10(-3) M) caused a similar reversal of the inhibition of ACh-induced relaxation by L-NAME in both groups. Serum NO levels were decreased and aortic MDA levels were increased in cadmium-treated rats as compared with control rats. However, the differences between the groups did not reach a statistical significance. These findings suggested that the reduction in endothelium-dependent relaxation may play a role in cadmium-induced hypertension as it was in many other hypertension models.
在几种动物模型中，内皮细胞舒张因子产生和/或释放异常与高血压的发生有关。据报道，在实验性诱导和遗传性高血压大鼠的胸主动脉中，内皮依赖性舒张功能受损。本研究将这些观察结果扩展到镉性高血压大鼠的胸主动脉。还研究了氧化状态改变的可能作用。通过腹腔注射1mg/kg/天的镉，持续15天诱导高血压。研究了乙酰胆碱（ACh，10(-9)-10(-4)M）和硝普钠（SNP，10(-10)-10(-5)M）对来自对照和镉性高血压大鼠的苯肾上腺素预收缩胸主动脉环产生的机械反应。测定了血清一氧化氮（NO）和主动脉丙二醛（MDA）水平。镉性高血压大鼠主动脉中ACh诱导的舒张减弱，而两组之间对SNP的舒张反应无显著差异。与对照大鼠相比，将主动脉环暴露于N(G)-硝基-L-精氨酸甲酯（L-NAME，10(-4)M）导致镉性高血压大鼠主动脉环对ACh舒张反应的抑制作用明显更大。两组用L-精氨酸（L-Arg，10(-3)M）孵育均引起L-NAME对ACh诱导舒张抑制作用的类似逆转。与对照大鼠相比，镉处理大鼠的血清NO水平降低，主动脉MDA水平升高。然而，两组之间的差异未达到统计学意义。这些发现表明，内皮依赖性舒张功能的降低可能在镉诱导的高血压中起作用，就像在许多其他高血压模型中一样。
