Abstract
Since hypertension is involved in redox and endocannabinoid systems disturbances, chronic administration of URB597, a FAAH inhibitor, that modulates the level of endocannabinoids, particularly anandamide, may regulate hypertensive metabolic consequences. Therefore, the aim of this study was to compare the effects of chronic administration of URB597 to SHRs and DOCA-salt rats on cardiac metabolism associated with redox system and lipid metabolism. It was shown that both primary and secondary hypertension is associated with enhanced cardiac inflammation and redox imbalance, resulting in increased lipid peroxidation products and endocannabinoids generation. URB597 administration decreasing FAAH activity enhanced endocannabinoids level, particularly in DOCA-salt heart. However in SHRs heart additional increase in MDA level was observed. Lipid mediators were involved in inflammatory response by PPARa expression in DOCA-salt rats and by PPARg expression in SHRs hearts. URB597 administration to normotensive rats also affected cardiac oxidative metabolism and endocannabinoids system, resulting in an enhanced level of MDA and endocannabinoids in Wistar rats. It can be concluded that lipid metabolism in heart rats with secondary hypertension and their control rats is more susceptible to chronic URB597 action and may lead to stronger cardiac disorders.
Published Version
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