Cannabidiol treatment changes myocardial lipid profile in spontaneously hypertensive rats

• Published in: Nutrition, metabolism, and cardiovascular diseases Vol. 34; no. 12; pp. 2817 - 2833
• Main Authors: Harasim-Symbor, Ewa, Bielawiec, Patrycja, Pedzinska-Betiuk, Anna, Weresa, Jolanta, Malinowska, Barbara, Konstantynowicz-Nowicka, Karolina, Chabowski, Adrian
• Format: Journal Article
• Language: English
• Published: Netherlands Elsevier B.V 13.07.2023
• Subjects: Cannabidiol; Fatty acid transporters; Fatty acid uptake; Lipids; Spontaneously hypertensive rats; Fatty acid transporters; Spontaneously hypertensive rats; Cannabidiol; Lipids; Fatty acid uptake
• ISSN: 0939-4753; 1590-3729; 1590-3729
• DOI: 10.1016/j.numecd.2023.07.007

Hypertension is a potent risk factor for cardiovascular diseases, which are the leading worldwide cause of death. Within time increased blood pressure (BP) induces cardiac contractile dysfunction, metabolic alternations, and eventually, heart failure, which makes hypertension an area for seeking safe therapies such as phytocannabinoids. In the present study spontaneously hypertensive rats (SHRs) were used as an experimental model of genetically induced hypertension, where cannabidiol (CBD) was applied as a potential treatment (intraperitoneally administered for 2 weeks, 10 mg/kg) for elevated BP and related metabolic disturbances. Langendorff working heart system, Western blotting as well as gas-liquid chromatography were applied to determine radiolabeled 3H-palmitate uptake, incorporation, and oxidation, protein expression, as well as the content and fatty acid composition of different lipid fractions in the left ventricle and plasma, respectively. Most importantly, we noticed that 2-week CBD treatment was effective in upregulating ex vivo3H-palmitate uptake, oxidation, and its incorporation into triacylglycerol and cholesterol fractions with concomitant lowering free fatty acid, diacylglycerol, and phospholipid fractions, which was in agreement with in vivo studies and alternations in protein expressions of lipoprotein lipase, carnitine palmitoyltransferase I, 3-hydroxyacyl-CoA dehydrogenase, diacylglycerol acyltransferase 1, and adipose triglyceride lipase as well as proteins associated with eicosanoid signaling pathways and extracellular matrix remodeling in the heart of hypertensive rats. Our study reveals that 2-week CBD administration substantially affects the energetic substrate milieu in cardiac muscle regarding fatty acids uptake and their further utilization without parallel significant alternations in cardiovascular parameters. [Display omitted] •CBD upregulates myocardial LCFAs uptake and oxidation in spontaneously hypertensive rats.•CBD promotes the elevation of myocardial neutral TAG pool in primary hypertension.•CBD protects the heart against the accumulation of biologically active DAG fraction in SHR.