Reduced cannabinoid receptors in bladder of metabolic syndrome rats

Purpose: To study the influence of metabolic syndrome on cannabinoid receptors in rats' bladder.

Materials and Methods: Male Sprague-Dawley rats were fed with high-fructose diet for nine weeks to induce metabolic syndrome. Another group was rats fed with normal chow. Metabolic syndrome associated profiles were measured. Bladder was harvested and Western blot, as well as RT-PCR tests, was applied for cannabinoid receptors expression. Pre-contracted bladder muscle strips were prepared in organ bath with acetylcholine or KCl. The effects of cannabionid receptor agonist on bladder strips were explored. The responses to protein kinase A (PKA) inhibitor and ATP-sensitive potassium channel (KATP) inhibitor were investigated.

Results: Metabolic syndrome was successfully induced in rats fed with high-fructose diet. Down-regulation of cannabinoid receptor protein and mRNA was found in metabolic syndrome rats. Pre-contracted bladder muscle strip tension decreased after cannabinoid receptor agonist treatment. The influence of cannabinoid receptor agonist on bladder muscle attenuated significantly in metabolic syndrome rats. Bladder muscle relaxation, which was induced by cannabinoid receptor agonist, was reduced after PKA inhibitor and KATP inhibitor treatment.

Conclusion: Cannabinoid receptors associated bladder relaxation might link to PKA and KATP pathway. The decreased effect of cannabinoid receptor on bladder muscle in metabolic syndrome rats might be related to down regulation of the receptor expression.