Key result
Clozapine depleted endothelial nitric oxide levels, enhanced oxidative stress, and impaired acetylcholine-induced aortic relaxation in isolated aortic strips.
Why the study?
Clozapine has been reported to produce myocarditis and other cardiac complications on repeated use, motivating an investigation into its role in vascular damage associated with nitric oxide metabolism.
Does clozapine disrupt endothelial nitric oxide signaling and antioxidant systems in isolated aortic strips?
Does clozapine disrupt endothelial nitric oxide signaling and antioxidant systems in isolated aortic strips?
Clozapine impairs endothelial nitric oxide signaling and increases oxidative stress, suggesting a mechanism for its associated cardiovascular complications.
Clozapine alters nitrite release in isolated vessels; leaves open contribution to clinical myocarditis or vascular risk.
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.
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Nair et al. (2019) studied this question. Clozapine was evaluated on Nitrite release, antioxidant systems, and vascular integrity (acetylcholine induced relaxation). Clozapine depleted endothelial nitric oxide levels, enhanced oxidative stress, and impaired acetylcholine-induced aortic relaxation in isolated aortic strips.
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