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

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.