The aim of this work was to determine whether Capsaicin may exert a vascular regulation through the activation of CB₁ and/or CB₂ receptors causing vasorelaxation in the rat aorta. Our results show the location of TRPV1 mainly in the endothelial and smooth muscle cells membrane. Nevertheless, Capsaicin caused vasorelaxation of this artery through a mechanism independent of TRPV1, since the specific antagonists Capsazepine and SB-366791 did not block the effect of Capsaicin. Because the significant expression of CB₁ and CB₂ receptors has been previously reported in the rat aorta, we used antagonists for these two receptors prior to the addition of Capsaicin. In these experiments, we found that the inhibition of CB₁ using AM281, decreases the vasorelaxant effect caused by Capsaicin. On the other hand, the vasorelaxant effect is not altered in the presence of the CB₂ receptor antagonist AM630. Furthermore, a partial decrease of the effect of Capsaicin was also seen when L-type calcium channels are blocked. A complete block of Capsaicin-induced vasorelaxation was achieved using a combination of Verapamil and AM281. In accordance to our results, Capsaicin-induced vasorelaxation of the rat aorta is neither dependent of TRPV1 or CB₂ receptors, but rather it is strongly suggested that a tandem mechanism between inactivation of L-type calcium channels and the direct activation of CB₁ receptors is involved. These findings are supported by CB₁ docking simulation which predicted a binding site on CB₁ receptors for Capsaicin.

ZnO nanoparticles (ZnONPs) have been shown to have therapeutic potential in some diseases such as diabetes and cancer. However, concentration-dependent adverse effects have also been reported. Studies which evaluate the effects of ZnONPs on the cardiovascular system are scarce. This study aimed to evaluate the cardiovascular effects of a low dose of ZnONPs administered chronically in healthy rats. Changes in dyslipidemia biomarkers, blood pressure, aortic wall structure, vascular contractility, and expression of cannabinoid receptors in the aorta wall were evaluated. Healthy rats were divided into two groups: control or treated (one, two, and three months). The treated rats received an oral dose of 10 mg/kg/day. The results showed that treatment with ZnONPs induced dyslipidemia from the first month, increasing atherosclerosis risk, which was confirmed by presence of atherosclerotic alterations revealed by aorta histological analysis. In in vitro assays, ZnONPs modified the aorta contractile activity in response to the activation of cannabinoid receptors (CB₁ and CB₂). The expression of CB₁ and CB₂ was modified as well. Moreover, ZnONPs elicited an increase in blood pressure. In conclusion, long-time oral administration of ZnONPs induce dyslipidemia and atherosclerosis eliciting alterations in aorta contractility, CB₁ and CB₂ receptors expression, and an increase in blood pressure in healthy rats.

Background/Objectives: To better understand the mechanisms involved in atherosclerosis, different models have been developed, but these fail when studying the progression of this disease. The purpose of this study was to standardize a new model of atherosclerosis progression in rats using Paigen-type modified atherogenic diet. Methods: The design included a control group (n = 16) and 64 rats with atherogenic Paigen-type diet subdivided into four subgroups with different doses (Athero 1, Athero 2, Athero 3, and Athero 4). The atherogenic diet was supplemented orally in sequential stages: 1) Hypervitaminic (1.5 mL/kg/day for 12 days) and 2) Hyperlipidic (48 days ad libitum). Blood pressure, heart rate, aortic histopathology, inflammatory biomarkers, and biochemical lipid and liver profiles were measured in all groups on days 30 and 60. Results: All Athero 1 rats were sacrificed due to a poisoning for vitamin D2 excess. Athero 2 rats were sacrificed at day 30 showing severe atherosclerotic lesions (grades V–VIII). Athero 3 rats showed mild lesions (I–IV) at day 30 and severe lesions (V–VIII) at day 60. Athero 4 rats showed mild lesions (I–IV) at days 30 and 60. Diet-dependent changes in blood pressure and heart rate were observed. Furthermore, glycemia, dyslipidemia, and liver profile were associated with the degree of atherosclerotic lesion. Conclusions: “Athero 3” atherogenic diet generates a stable model to study the progress of atherosclerosis in rats.

Previous studies have suggested a role of the endocannabinoid system in metabolic diseases, such as diabetes. We investigated the effect of diabetes on cannabinoid receptor type 1 (CB₁) expression and cannabinoid-induced vasorelaxation in rat aorta rings. Aortas from healthy rats and from rats with experimentally induced diabetes were used to compare the vasorelaxant effect of the cannabinoid agonist arachidonylcyclopropylamide (ACPA) and CB₁ expression and localization. After 4–8 weeks of diabetes induction, CB₁ receptor expression and CB₁ phosphorylation were higher in aortic rings, in association with greater vasorelaxation induced by the CB₁ agonist ACPA compared to healthy rats. The vasorelaxant effect observed in healthy rats is similar throughout the study. Further studies are needed to elucidate the implications of CB₁ receptor overexpression in diabetes and its influence on the progression of the cardiovascular complications of this metabolic disease.