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Open AccessArticle

Chronic Cannabidiol Administration Fails to Diminish Blood Pressure in Rats with Primary and Secondary Hypertension Despite Its Effects on Cardiac and Plasma Endocannabinoid System, Oxidative Stress and Lipid Metabolism

1
Department of Experimental Physiology and Pathophysiology, Medical University of Białystok, 15-222 Białystok, Poland
2
Department of Analytical Chemistry, Medical University of Białystok, 15-222 Białystok, Poland
3
Department of Pharmacology and Toxicology, University of Bonn, 53127 Bonn, Germany
4
Department of Physiology, Medical University of Białystok, 15-222 Białystok, Poland
*
Author to whom correspondence should be addressed.
Int. J. Mol. Sci. 2020, 21(4), 1295; https://doi.org/10.3390/ijms21041295
Received: 4 February 2020 / Revised: 13 February 2020 / Accepted: 13 February 2020 / Published: 14 February 2020
We investigated the influence of cannabidiol (CBD) on blood pressure (BP) and heart rate (HR) in spontaneously (SHR) and deoxycorticosterone (DOCA-salt) hypertensive rats. Hypertension was connected with increases in cardiac and plasma markers of lipid peroxidation in both models, whereas cardiac endocannabinoid levels decreased in SHR and increased in DOCA-salt. CBD (10 mg/kg once a day for 2 weeks) did not modify BP and HR in hypertension but counteracted pro-oxidant effects. Moreover, it decreased cardiac or plasma levels of anandamide, 2-arachidonoylglycerol and oleoyl ethanolamide in DOCA-salt and inhibited the activity of fatty acid amide hydrolase (FAAH) in both models. In the respective normotensive control rats, CBD increased lipid peroxidation, free fatty acid levels and FAAH activity. In conclusion, chronic CBD administration does not possess antihypertensive activity in a model of primary and secondary (DOCA-salt) hypertension, despite its antioxidant effect. The latter may be direct rather than based on the endocannabinoid system. The unexpected CBD-related increase in lipid peroxidation in normotensive controls may lead to untoward effects; thus, caution should be kept if CBD is used therapeutically. View Full-Text
Keywords: 2-arachidonoylglycerol; anandamide; cannabidiol; cannabinoid receptor; SHR; DOCA-salt; endocannabinoids; oxidative stress 2-arachidonoylglycerol; anandamide; cannabidiol; cannabinoid receptor; SHR; DOCA-salt; endocannabinoids; oxidative stress
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Remiszewski, P.; Jarocka-Karpowicz, I.; Biernacki, M.; Jastrząb, A.; Schlicker, E.; Toczek, M.; Harasim-Symbor, E.; Pędzińska-Betiuk, A.; Malinowska, B. Chronic Cannabidiol Administration Fails to Diminish Blood Pressure in Rats with Primary and Secondary Hypertension Despite Its Effects on Cardiac and Plasma Endocannabinoid System, Oxidative Stress and Lipid Metabolism. Int. J. Mol. Sci. 2020, 21, 1295.

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