Δ9-tetrahydrocannabinol treatment improved endothelium-dependent relaxation on streptozotocin/nicotinamide-induced diabetic rat aorta.

Abstract

Objective: In this study, we investigated the possible effect of Δ(9)-tetrahydrocannabinol (THC), a peroxisome proliferator-activated receptor gamma (PPARγ) agonist, on metabolic control and vascular complications of diabetes in streptozotocin/nicotinamide (STZ/NIC) induced type 2 diabetes mellitus.

Material and methods: Type 2 diabetes was induced with 65 mg/kg STZ, 15 minute later 85 mg/kg NIC was given intraperitoneally (i.p.) to rats. Three days after diabetes induction, THC (3 mg/kg/day, i.p.) was given for 7 days to diabetic rats. Body weight and plasma glucose levels of rats were measured in all groups before and at the end of 3 weeks after diabetes induction. Acetylcholine (Ach) and sodium nitroprusside (SNP) potency and maximum relaxant effects were calculated on aortic rings pre-contracted with noradrenaline (NA).

Results: At the end of 3 weeks, blood glucose levels of diabetic group significantly increased in comparison with the control group. Increased plasma glucose levels were significantly decreased by the treatment of THC. Ach induced relaxation was impaired whereas endothelium-independent relaxation to SNP was unaffected on isolated diabetic rat aorta. THC treatment enhanced Ach induced relaxation on diabetic rat aortas.

Discussion: These results suggested that THC improved endothelium-dependent relaxation in STZ/NIC induced diabetic rat aorta and that these effects were mediated at least in part, by control of hyperglycemia and enhanced endothelial nitric oxide bioavailability.