Efeitos do tratamento crônico com extrato de cannabis sativa rico em canabidiol (CBD) sobre a função vascular em modelo murino de aterosclerose

Abstract

Atherosclerosis is a chronic inflammatory disease associated with endothelial dysfunction, oxidative stress, and alterations in the lipid profile, and it is one of the leading causes of cardiovascular morbidity and mortality. Cannabidiol (CBD), a phytocannabinoid derived from Cannabis sativa, exhibits anti-inflammatory and antioxidant properties and has been investigated as a potential therapeutic agent in cardiovascular diseases. The present study aimed to evaluate the effects of chronic treatment with a Cannabis sativa extract rich in CBD on vascular function and biochemical profile in a murine model of atherosclerosis (apoE⁻/⁻ mice). The animals were divided into three groups: C57BL/6 control, apoE⁻/⁻ treated with vehicle (olive oil), and apoE⁻/⁻ treated with CBD (30 mg/kg, by gavage, for 14 days). Plasma lipid profile (total cholesterol, HDL, and non-HDL) and vascular reactivity were assessed in aortic artery rings with and without functional endothelium through concentration–response curves to phenylephrine (PHE), acetylcholine (ACh), and sodium nitroprusside (SNP). The results demonstrated that apoE⁻/⁻ animals exhibited significant hypercholesterolemia compared to the control group (746,1 ± 64,27 vs. 86,61 ± 7,20), with no modification after CBD treatment (764,6 ± 50,80 vs. 746,1 ± 64,27). Regarding vascular reactivity, the untreated apoE⁻/⁻ group showed reduced vasoconstriction to PHE (40,30 ± 4,93 vs. 70,97 ± 7,56), with an increase in this response following CBD administration (66,8 ± 5,92 vs. 40,30 ± 4,93). Endothelium-dependent vasodilation (ACh) did not differ between control and apoE⁻/⁻ groups, nor was it altered by CBD treatment. Similarly, the response to SNP, an endothelium-independent vasodilator, did not differ among the groups. It can be concluded that CBD treatment, under the conditions evaluated, did not alter the lipid profile but modulated vascular reactivity, particularly the contractile response. These findings suggest a possible influence of the vehicle used and reinforce the need for additional studies to clarify the underlying mechanisms.