Clozapine Disrupts Endothelial Nitric Oxide Signaling and Antioxidant System for its Cardiovascular Complications

被引:13
作者
Nair, Gayathri M. [1 ]
Skaria, Dona Sheba [1 ]
James, Teenu [1 ]
Kanthlal, S. K. [1 ]
机构
[1] Amrita Vishwa Vidyapeetham, Dept Pharmacol, Amrita Sch Pharm, AIMS Hlth Sci Campus, Kochi, Kerala, India
关键词
nitric oxide; cardiovascular diseases; adverse drug reactions;
D O I
10.1055/a-0991-7684
中图分类号
R914 [药物化学];
学科分类号
100701 ;
摘要
Objective Many drugs in current practice require additional safety labels in order to prevent potential risks to the major organ system. Psychotropic agent clozapine has been reported to produce myocarditis and other cardiac complications on repeated use. Our study aimed to establish the role of clozapine in vascular damage associated with nitric oxide metabolism. Method Isolated aortic strips incubated with clozapine at different dose levels were estimated for nitrite release and antioxidant systems such as glutathione and catalase. Vascular integrity assessment was performed by recording the acetylcholine induced relaxation of phenyephrine pre-contracted aorta. Result From our study, it was found that clozapine depletes the nitric oxide level in the endothelium and enhance the oxidative stress. The aorta fails to relax completely after the addition of acetylcholine indicates the deranged eNOS signaling in the endothelium. Conclusion From the experimental findings, it was concluded that clozapine could depress the eNOS regulation and thereby perhaps initiates cardiovascular complications through subsequent vascular events
引用
收藏
页码:695 / 698
页数:4
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