The effects of the urotensin-II receptor antagonist palosuran treatment on the corpora cavernosa of streptozotocin-induced diabetic rats

IF 2.4 3区医学 Q2 UROLOGY & NEPHROLOGY

Asian Journal of Urology Pub Date : 2025-01-01 DOI:10.1016/j.ajur.2024.02.010

Murat Olukman , Cenk Can , Sibel Ülker , Yiğit Uyanikgil , Türker Çavuşoğlu , Neslihan Düzenli , Deniz Coşkunsever , Fatma G. Kozcu

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Abstract

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.

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来源期刊

Asian Journal of Urology UROLOGY & NEPHROLOGY-

CiteScore

4.00

自引率

3.80%

发文量

100

审稿时长

4 weeks

期刊介绍： Asian Journal of Urology (AJUR), launched in October 2014, is an international peer-reviewed Open Access journal jointly founded by Shanghai Association for Science and Technology (SAST) and Second Military Medical University (SMMU). AJUR aims to build a communication platform for international researchers to effectively share scholarly achievements. It focuses on all specialties of urology both scientifically and clinically, with article types widely covering editorials, opinions, perspectives, reviews and mini-reviews, original articles, cases reports, rapid communications, and letters, etc. Fields of particular interest to the journal including, but not limited to: • Surgical oncology • Endourology • Calculi • Female urology • Erectile dysfunction • Infertility • Pediatric urology • Renal transplantation • Reconstructive surgery • Radiology • Pathology • Neurourology.