Cardio-renal effects of chronic administration with CB2 agonist AM1241 and CB2 antagonist AM630 in rats with diet induced obesity

It is widely recognised that obesity elicits a number of comorbidities including heart and kidney disease. The progression of these diseases is frequently exacerbated by other clinical factors associated with obesity such as hypertension and metabolic imbalance. Obesity associated pathology includes cardiac and renal hypertrophy, which can lead to an increased risk of developing ischemic heart disease, stroke and hypertension, in addition to a decreased glomerular filtration rate and increased urinary protein excretion. Previous research has indicated that chronic activation of the cannabinoid receptor 2 (CB2) may have a protective role in ameliorating renal function decline associated with diabetic nephropathy and a range of cardiomyopathies. It is still unclear however what role the CB2 receptor may play in modulating cardiac and renal tissue in the obese state. The aim of the current study was to investigate whether activation or inhibition of the CB2 receptor in an obese rat model altered cardiac and renal tissue in diet induced obesity. Following nine weeks of a high fat diet, male Sprague Dawley rats were injected with either 3 mg/kg body weight of the CB2 agonist AM1241, or 0.3 mg/kg body weight of the CB2 antagonist AM630, or saline for six weeks, while continuing on the high fat diet. Diet induced obesity was confirmed via comparison to animals fed standard chow and treated with saline. Urine was collected and blood pressure measured throughout the treatment period. Following the 6 weeks of treatment the heart and kidneys were harvested and weighed. The CB2 antagonist group showed significant changes to both the heart and kidneys, with organ weight relative to body weight ratio significantly higher than the high fat saline control group (p