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Cannabidiol treatment changes myocardial lipid profile in spontaneously hypertensive rats
Ewa Harasim-Symbor1, Patrycja Bielawiec1, Anna Pedzinska-Betiuk2
1Department of Physiology, Medical University of Bialystok, 15-222, Bialystok, Poland.
Insights
Cannabidiol (CBD) treatment in hypertensive rats improved cardiac fatty acid metabolism. This phytocannabinoid therapy enhanced fatty acid utilization in the heart without significantly altering blood pressure.
Area of Science:
- Cardiovascular Research
- Metabolic Science
- Pharmacology
Background:
- Hypertension is a major risk factor for cardiovascular diseases and heart failure.
- Phytocannabinoids are being explored for safe therapeutic interventions.
- Elevated blood pressure leads to cardiac dysfunction and metabolic changes.
Purpose of the Study:
- To investigate the effects of cannabidiol (CBD) on blood pressure and cardiac metabolism in spontaneously hypertensive rats (SHRs).
- To assess CBD's impact on fatty acid uptake, utilization, and related protein expression in the heart.
Main Methods:
- Spontaneously hypertensive rats (SHRs) received CBD (10 mg/kg) intraperitoneally for 2 weeks.
- Langendorff working heart system, Western blotting, and gas-liquid chromatography were employed.
- Analysis included radiolabeled palmitate uptake, oxidation, incorporation, protein expression, and lipid profiles.
Main Results:
- CBD treatment upregulated cardiac fatty acid uptake, oxidation, and incorporation into triacylglycerol and cholesterol.
- CBD reduced levels of free fatty acids, diacylglycerols, and phospholipids in the heart.
- Alterations in key metabolic enzymes and signaling pathways were observed in hypertensive rat hearts.
Conclusions:
- Two-week CBD administration significantly impacts cardiac fatty acid metabolism in hypertensive rats.
- CBD enhances fatty acid utilization in the heart without significant changes in cardiovascular parameters.
- CBD shows potential in modulating cardiac energetic substrates in hypertension.
Background And Aims:
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.
Methods And Results:
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.
Conclusion:
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.
