Effect of hypertension on myocardial cannabinoid CB1 receptor expression

The endocannabinoid, anandamide, and cannabinoid CB1 receptors have been implicated in cardiac remodeling. Further, anandamide was shown to be a substrate for the cyclooxygenase‐2 (COX‐2) enzyme which has been linked to cardiac remodeling. This study was designed to determine the expression level of CB1 protein in cardiac remodeling secondary to abdominal aortic constriction model of pressure overload (PO). The effects of the COX‐2 selective inhibitor, Nimesulide (Nime), on the adverse remodeling changes and CB1 protein levels were also further investigated. In vivo LV volume and function were assessed by a pressure/volume catheter at 14 and 28 days post surgery in four groups (n= 4–6 per group) of male SD rats: 1)sham‐operated; 2)untreated PO; 3)prevention treatment with Nime (10mg/kg/d); and 4)intervention treatment with Nime (10mg/kg/d). Relative to sham, LV/body weight index was significantly increased and end diastolic volume was significantly decreased at the 14 and 28 day time points in untreated PO animals. Nime treatment significantly attenuated these changes. Myocardial CB1 protein level was significantly decreased at 14 and 28 days in the untreated PO groups as compared to sham values. Treatment with Nime did not prevent the PO induced decrease in CB1 protein level. The beneficial remodeling changes by COX‐2 inhibition do not appear to be mediated via CB1 receptors. AHA 09BGIA2090065 UM‐COBRE