| Summary: | 碩士 === 國防醫學院 === 藥理學研究所 === 87 === Imbalance between reactive oxygen species (ROS) and antioxidant defense system lead to tissue damage has been reported. It is well established that various diseases (e.g. hypertension, artherosclerosis, diabetes and ischemia-reperfusion injury etc.) were positively correlated with the level of ROS formation. The reason is that ROS directly attack on the cellular biomacromolecules, e.g. lipid, protein, polysaccharide and nucleic acid, and inactivate cellular mediators, e.g. nitric oxide, then, finally, cause tissue damage and dysfunction. However, it has been demonstrated that the superoxide anion in SHR is greater than that in WKY rats. According to our and other laboratory studies showed that the vasodilator response to acetylcholine (ACh) and angiotensin II-induced vasocontration in SHR is significantly lower than that in WKY rats. Recently, it has been shown that a commonly used vasodilator, hydralazine, possesses potentially antioxidant properties. On the basis of the above rationale, the aim of this study is to evaluate whether hydralazine can improve the impaired vasodilator response to ACh in SHR and prevent desensitization-induced by angiotensin II in WKY rats. Experiments were performed in isolated aortic rings preparation. The experimental results of both in vivo and in vitro studies demonstrated that hydralazine not only significantly improved vasodilator response to ACh in SHR, but also significantly reduced superoxide anion and increased NO formation in vascular tissue. On the other hand, angiotensin II-induced desensitization in SHR was greater than that in WKY. However, this desensitization can be prevented by the pretreatment of hydralazine both in SHR and WKY. Meanwhile, hydralazine also significantly reduced the superoxide anion production which was induced by angiotension II. Furthermore, hydralazine only prevented superoxide anion-but not hydrogen peroxide-induced desensitization. Thus, the main mechanism of action of hydralazine in the prevention of angiotensin-induced desensitization may mainly mediate through by the inhibition of superoxide anion formation. Finally, the expression of GRK2 in the membrane of vascular smooth muscle in SHR is significantly higher than that in WKY. Also, this GRK2 expression in the membrane can be inhibited by the treatment with hydralazine. In conclusion, our results suggest that ROS may play an important role in the modulation of vascular response to ACh and angiotensin II in SHR. However, this impairment of vascular responses to ACh and desensitization-induced by angiotensin II were significantly prevented by the pretreatment with hydralazine. Therefore, we suggest that hydralazine may mediate through by the inhibition of NADH oxidase then to reduce superoxide anion formation in SHR.
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