Δ9-Tetrahydrocannabinol Prevents Cardiovascular Dysfunction in STZ-Diabetic Wistar-Kyoto Rats

Rebecca K. Vella, Douglas J. Jackson, Andrew S. Fenning

The aim of this study was to determine if chronic, low-dose administration of a nonspecific cannabinoid receptor agonist could provide cardioprotective effects in a model of type I diabetes mellitus. Diabetes was induced in eight-week-old male Wistar-Kyoto rats via a single intravenous dose of streptozotocin (65 mg kg-1). Following the induction of diabetes, Δ9-tetrahydrocannabinol was administered via intraperitoneal injection (0.15 mg kg-1 day-1) for an eight-week period until the animals reached sixteen weeks of age. Upon completion of the treatment regime, assessments of vascular reactivity and left ventricular function and electrophysiology were made, as were serum markers of oxidative stress and lipid peroxidation. Δ9-Tetrahydrocannabinol administration to diabetic animals significantly reduced blood glucose concentrations and attenuated pathological changes in serum markers of oxidative stress and lipid peroxidation. Positive changes to biochemical indices in diabetic animals conferred improvements in myocardial and vascular function. This study demonstrates that chronic, low-dose administration of Δ9-tetrahydrocannabinol can elicit antihyperglycaemic and antioxidant effects in diabetic animals, leading to improvements in end organ function of the cardiovascular system. Implications from this study suggest that cannabinoid receptors may be a potential new target for the treatment of diabetes-induced cardiovascular disease.