Nair Gayathri M, Skaria Dona Sheba, James Teenu, Kanthlal S K
Department of Pharmacology, Amrita School of Pharmacy, Amrita Vishwa Vidyapeetham, AIMS Health Science Campus, Kochi, Kerala, India.
Drug Res (Stuttg). 2019 Dec;69(12):695-698. doi: 10.1055/a-0991-7684. Epub 2019 Sep 9.
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.
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.
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.
From the experimental findings, it was concluded that clozapine could depress the eNOS regulation and thereby perhaps initiates cardiovascular complications through subsequent vascular events.
目前临床使用的许多药物需要额外的安全标签，以防止对主要器官系统造成潜在风险。据报道，精神药物氯氮平反复使用会导致心肌炎和其他心脏并发症。我们的研究旨在确定氯氮平在与一氧化氮代谢相关的血管损伤中的作用。
用不同剂量水平的氯氮平孵育离体主动脉条，检测亚硝酸盐释放以及谷胱甘肽和过氧化氢酶等抗氧化系统。通过记录乙酰胆碱诱导的去氧肾上腺素预收缩主动脉的舒张情况来进行血管完整性评估。
从我们的研究中发现，氯氮平会消耗内皮中的一氧化氮水平并增强氧化应激。添加乙酰胆碱后主动脉未能完全舒张，这表明内皮中的内皮型一氧化氮合酶（eNOS）信号紊乱。
根据实验结果得出结论，氯氮平可能会抑制eNOS调节，从而可能通过随后的血管事件引发心血管并发症。
