Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2020 Jul 10;10(7):1022.
doi: 10.3390/biom10071022.

The FAAH Inhibitor URB597 Modulates Lipid Mediators in the Brain of Rats with Spontaneous Hypertension

Michał Biernacki  1 , Marta Baranowska-Kuczko  2 , Gabriella N Niklińska  3 , Elżbieta Skrzydlewska  1
Affiliations

The FAAH Inhibitor URB597 Modulates Lipid Mediators in the Brain of Rats with Spontaneous Hypertension

Michał Biernacki et al. Biomolecules. .

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.

Keywords: URB597; endocannabinoid system; lipid peroxidation products; rat brain; spontaneous hypertension.

PubMed Disclaimer

Conflict of interest statement

The authors have no conflicts of interest to declare.

Figures

Figure 1
Figure 1
The activities/levels of antioxidant parameters in the brain of rats with spontaneous hypertension and hypertensive rats after URB597 administration. Data points represent the mean ± SD, n = 6; (a, significantly different from the Wistar–Kyoto (WKY) group, p < 0.05; b, significantly different from the of spontaneously hypertensive rats (SHR) group, p < 0.05).
Figure 2
Figure 2
The levels of Nrf2 and its activator (p62) and inhibitors (Keap1, Bach1) as well as HO-1 in the brain of spontaneously hypertensive rats and hypertensive rats after URB597 administration. The expression of the examined proteins is shown compared to the control groups. Data points represent the mean ± SD, n = 6; (a, significantly different from the WKY group, p < 0.05; b, significantly different from the SHR group, p < 0.05).
Figure 3
Figure 3
The levels of phospholipid and free fatty acids in the brain of spontaneously hypertensive rats and hypertensive rats after URB597 administration. Data points represent the mean ± SD, n = 6; (a, significantly different from the WKY group, p < 0.05; b, significantly different from the SHR group, p < 0.05).
Figure 4
Figure 4
The levels of lipid peroxidation products (MDA and 8-isoPGF2) in the brain of spontaneously hypertensive rats and hypertensive rats after URB597 administration. Data points represent the mean ± SD, n = 6; (a, significantly different from the WKY group, p < 0.05; b, significantly different from the SHR group, p < 0.05.
Figure 5
Figure 5
The level of endocannabinoids (AEA, 2-AG) and activity of enzyme-degrading endocannabinoids (FAAH) as well as expression of receptors (CB1, CB2, GPR55) in the brain of spontaneously hypertensive rats and hypertensive rats after URB597 administration. The expression of the examined proteins is shown compared to the control groups. Data points represent the mean ± SD, n = 6; (a, significantly different from the WKY group, p < 0.05; b, significantly different from the SHR group, p < 0.05).
See this image and copyright information in PMC

Similar articles

See all similar articles

Cited by

See all "Cited by" articles

References

    1. Frances A., Sandra O., Lucy U. Vascular cognitive impairment, a cardiovascular complication. World J. Psychiatry. 2016;6:199–207. doi: 10.5498/wjp.v6.i2.199. - DOI - PMC - PubMed
    1. Brito R., Castillo G., González J., Valls N., Rodrigo R. Oxidative stress in hypertension: Mechanisms and therapeutic opportunities. Exp. Clin. Endocrinol. Diabetes Off. J. Ger. Soc. Endocrinol. Ger. Diabetes Assoc. 2015;123:325–335. doi: 10.1055/s-0035-1548765. - DOI - PubMed
    1. Di Meo S., Reed T.T., Venditti P., Victor V.M. Role of ROS and RNS Sources in Physiological and Pathological Conditions. Oxid. Med. Cell. Longev. 2016;2016:1–44. doi: 10.1155/2016/1245049. - DOI - PMC - PubMed
    1. Sun W., Wang X., Hou C., Yang L., Li H., Guo J., Huo C., Wang M., Miao Y., Liu J., et al. Oleuropein improves mitochondrial function to attenuate oxidative stress by activating the Nrf2 pathway in the hypothalamic paraventricular nucleus of spontaneously hypertensive rats. Neuropharmacology. 2017;113:556–566. doi: 10.1016/j.neuropharm.2016.11.010. - DOI - PubMed
    1. Figueira L., Israel A. Effect of Valsartan on Cerebellar Adrenomedullin System Dysregulation during Hypertension. Cerebellum Lond. Engl. 2017;16:132–141. doi: 10.1007/s12311-016-0780-2. - DOI - PubMed

MeSH terms