Metabolic Syndrome Induced Bladder Cannabinoid Receptor Changes in the Fructose-Fed Rats

Objectives: To investigate the effect of metabolic syndrome on the bladder cannabinoid receptors 1 and 2 (CB1/CB2) expression and function in the fructose-fed rats (FR). Methods: Adult male Sprague–Dawley rats were divided into two groups: (i) Control rats fed with normal chow; and (ii) Rats fed with high-fructose diet (FR) for 9 weeks. The body weight, blood pressure, plasma sugar, insulin, triglyceride and cholesterol were measured. Bladder muscle strips were prepared in organ bath and pre-contracted with 1 µM/L acetylcholine (ACh) or 50 mM/L KCl. The relaxation responses to CB1/CB2 agonist Bay59-3047 (0.01–1 µM/L) were recorded. The effects of CB1 antagonist AM251, CB2 antagonist AM630, protein kinase A (PKA) inhibitor H-89 and ATP-sensitive potassium channel (K_{ATP )} inhibitor glibenclamide on the Bay59-3047-induced response were tested. Western blotting and real-time polymerase chain reaction (RT-PCR) analyses were performed for bladder CB1/CB2 receptors. Results: Significant increases of body weight, blood pressure, plasma glucose, insulin, cholesterol and triglyceride levels were found in the FR. Bay59-3047 reduced ACh and KCl pre-contracted bladder strip tension in a dose-dependent fashion. The relaxation responses were significantly decreased in the FR. The Bay59-3047-induced relaxation was attenuated by AM251, glibenclamide and H-89. Western blotting and RT-PCR showed decreased expressions of FR bladder CB1 and CB2 receptor protein and mRNA. Conclusion: CB1/CB2 receptors mediate rat bladder relaxation through the PKA and K_ATP pathway. The CB1 receptor may play a more prominent role. The response is decreased in the FR bladder due to reduced expressions of the cannabinoid receptors.