Purpose: Cardiovascular diseases cause high rates of morbidity and mortality worldwide. The most common cardiovascular diseases are atherosclerosis and hypertension. We previously developed mice deficient in both low-density lipoprotein receptor and cannabinoid type 1 receptor (LDLR-CB1R double knockout [KO] mice), which develop atherosclerosis and high cholesterol levels if kept on a high-fat diet, to study the role of CB1Rs in vascular responses. Previously, we found that vasodilation responses to a high-fat diet were attenuated in LDLR-KO mice and improved in the absence of CB1Rs. Earlier, we also found that CB1R inhibition augmented contractile functions. In this study, we aimed to demonstrate the effects of a high-fat diet and CB1Rs on vasoconstriction of the aorta induced by angiotensin II (Ang II). Materials and methods: Experiments were performed on LDLR-CB1R double KO and wild type mice, kept on a high-fat or control diet for 5 months. After anaesthesia with Euthasol (pentobarbital sodium, 50 mg kg
1), the thoracic and abdominal aortas were isolated. Segments of the abdominal aorta were isolated for myography to obtain Ang II-induced (1-100 nM) contractile responses. Results: We found that Ang II-induced contractions significantly increased in the high-fat diet groups (P < 0.05) in the LDLR
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, CB1R wild type mice, which was not effectively modulated by CB1Rs. However, contractions were stronger on the control diet in the CB1R-KO mice compared to the wild type mice. Conclusion: Our results indicate that LDLR-KO mice on a high-fat diet develop atherosclerosis. Angiotensin II-induced contractions are not effectively influenced by CB1Rs, as higher contractile properties are retained in CB1R-KO mice. Based on this and our previous observations, higher contractile properties with higher vasorelaxation create a greater range for vasomotion in the absence of CB1Rs.  Kulcsszavak: angiotensin II, atherosclerosis, CB1 receptor, LDL receptor, endocannabinoid, vascular remodelling, high-fat diet