Impaired vessel relaxation response and increased infarct size in smooth muscle cannabinoid receptor 1 knockout mice

Cannabinoids are reported to regulate cardiovascular functions. Cannabinoid receptors 1 (CB1Rs) are widely expressed in both the neuronal system and vascular system, but the contribution of CB1Rs in vascular smooth muscle (CB1R^SM) to cardiovascular functions is not clear yet. In this research, we analyzed the effects of CB1R^SM on blood pressure, vasoconstriction, and vasodilation abilities by using conditionally CB1R knockout mice (CB1R^SMKO). The results show no significant difference in basal blood pressure between the conscious CB1R^SMKO and control mice, indicating that CB1R^SM is not essential for basal blood pressure maintenance. The constriction of the CB1R^SMKO mesenteric artery in vitro was not significantly altered compared with that of the control mice. In contrast, the relaxation to CB1R agonist 2-AG or WIN55212-2 was decreased in CB1R^SMKO vessels, suggesting that activation of CB1R^SM mediates the vasodilation effect of cannabinoids. Ischemia stroke mouse model was used to further identify the potential function of CB1R^SM in pathological conditions, and the results showed that the infarct volume in CB1R^SMKO mice is significantly increased compared with the control littermates. These results suggest that vascular CB1R may not play a central role in basal vascular health maintenance but is protective in ischemia states, such as stroke. The protection function may be mediated, at least partly, by the relaxation effect of CB1R^SM-dependent activities of endocannabinoids.