Abstract
Hypertension is accompanied by oxidative stress, which can be modified by the functioning of the endocannabinoid system playing a prominent modulatory role in the brain. The present study tested whether chronic administration of the fatty acid amide hydrolase (FAAH) inhibitor [3-(3-carbamoylphenyl) phenyl]N-cyclohexylcarbamate (URB597) to rats with primary hypertension (SHR) can modify redox balance and consequently brain phospholipid metabolism. Experiments were conducted using SHRs and normotensive control Wistar–Kyoto rats treated by intraperitoneal injection with URB597 for 14 days. The biochemical parameters were assayed in the rats’ brains. Inhibition of FAAH activity by URB597 resulted in an increase in anandamide and GPR55 receptor levels, as well as a decrease in CB2 receptor expression. However, there was a simultaneous increase in Nrf2 expression, as well as Cu, Zn-SOD, GSH-Px, glutathione reductase activity, and vitamin E levels in brain tissue of SHR rats. Consequently, URB597 caused a decrease in levels of phospholipid fatty acids and MDA, and an increase in free fatty acids. Given the importance of maintaining redox balance for brain function, the results of this study point to endocannabinoids as a potential therapeutic target for preventing brain metabolic disorders in hypertension.
Highlights
Hypertension is an important risk factor for cerebrovascular diseases, including stroke
Subsequent research has demonstrated that antioxidant therapy promotes the reduction of blood pressure in the hypothalamus of spontaneously hypertensive rats (SHRs), and that these effects are mediated by reduced oxidative stress and inflammation [5]
This study demonstrates that AEA modifies the redox balance of brain cells by reducing oxidative phospholipid modifications
Summary
Hypertension is an important risk factor for cerebrovascular diseases, including stroke. Physiological levels of ROS are important for maintaining proper homeostatic functioning of brain cells, whereas ROS overload can exceed the antioxidant abilities and lead to oxidative stress [3]. Hypertension promotes a reduction in activity of antioxidant enzymes such as Cu-Zn-SOD, CAT, GSH-Px, and GSH level [4,5]. The transcription factor Nrf plays an important role in maintaining the proper level of antioxidant proteins. Nrf is responsible for the biosynthesis of cytoprotective antioxidant proteins, but expression of Nrf is reduced in the brains of hypertensive rats [6]. Subsequent research has demonstrated that antioxidant therapy promotes the reduction of blood pressure in the hypothalamus of spontaneously hypertensive rats (SHRs), and that these effects are mediated by reduced oxidative stress and inflammation [5]
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