Objective
This study aimed to investigate the effects of treatment with palosuran, a urotensin receptor blocker, on molecular changes in the corpora cavernosa (CC) in diabetic rats.
Methods
Streptozotocin-induced diabetic rats were treated with palosuran 300 mg/kg per day for 6 weeks. Contraction of CC induced by potassium chloride, phenylephrine, and NG-nitro-L-arginine methyl ester and relaxation of CC induced by electrical field stimulation (EFS) and sodium nitroprusside (SNP) (endothelium-dependent and endothelium-independent stimuli, respectively), and Y-27632 (Rho-kinase inhibitor) were examined in organ baths. Direct contraction or relaxation induced by palosuran and urotensin-II (U-II) were also evaluated. The expression levels of nitric oxide synthetases (NOSs), RhoA, oxidative stress regulators, and U-II were analyzed by Western blotting or immunohistochemistry.
Results
Induction of diabetes in rats resulted in the decreased relaxant response to SNP, decreased pD2 value of SNP, attenuated relaxant response to Y-27632 as well as the decreased RhoA expression in CC. Palosuran treatment of diabetic rats reversed all of these parameters; however, it further impaired the already weakened relaxation of diabetic CC in response to EFS. Although induction of diabetes did not change U-II expression in CC significantly, palosuran treatment reduced U-II expression in diabetic CC. The expression level of nNOS was lowered in diabetic CC; however, palosuran treatment did not change the decreased the neuronal NOS expression. In vitro exposure of diabetic CC strips to palosuran produced a direct relaxant response.
Conclusion
Palosuran treatment did not affect the expression of NOSs or reduce nitrergic conduction induced by EFS stimulation in diabetic CC. However, while directly triggering a relaxant response, it did not induce a prominent contraction either by decreasing U-II expression, or increasing the sensitivity of CC to nitric oxide which suggested that palosuran has the potential to support erectile function. Further and comprehensive studies are required to clarify this issue.
扫码关注我们
求助内容:
应助结果提醒方式:
