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In vitro effect of relaxin in the rat corpus cavernosum under hyperglycemic and normoglycemic conditions

International Journal of Impotence Research volume 36, pages 72–77 (2024)Cite this article

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Abstract

Relaxin, an endogenous peptide hormone, elicits vascular relaxation by its direct effect or by modulating the endothelium-dependent relaxation response and is clinically evaluated for the treatment of coronary artery disease. However, its effect on penile tissue has not been explored yet. This study aimed to investigate the effect of serelaxin, recombinant human relaxin-2, on rat corpus cavernosum (CC) under healthy and hyperglycemic conditions. Strips of CC obtained from thirty-nine male Wistar rats weighing 300–350 g were used in organ baths for isometric tension studies to investigate the serelaxin-mediated relaxation (10−12–10−7 M) under normoglycemic conditions and the effect of serelaxin on endothelium-dependent [nitric oxide (NO)- and prostacyclin-mediated] relaxation responses under hyperglycemic conditions. The in vitro hyperglycemia model was created by 3 h of incubation with 44 mM glucose monohydrate +120 μM methylglyoxal. NO-dependent relaxation responses were evaluated by cumulative acetylcholine (10−9–10−4 M) administration in the presence of indomethacin (10−6 M). Prostacyclin-mediated relaxation was evaluated by cumulative administration of iloprost (10−9–10−6 M), a prostacyclin analog. Maximum relaxation responses to serelaxin were not significantly different compared to the time-control (p = 0.480). Three hours of incubation of rat CC in hyperglycemic conditions impaired NO- and prostacyclin-mediated relaxation responses (p = 0.032 and p = 0.047, respectively). Serelaxin coincubation worsened NO-mediated relaxation responses (p = 0.016) but did not affect prostacyclin-mediated responses (p = 0.425). Together, our results demonstrate that in vitro administration of serelaxin does not cause relaxation in penile tissue and short-term in vitro serelaxin treatment in hyperglycemic conditions mimicked diabetes modulates endothelium-dependent responses by worsening NO-mediated responses. Serelaxin exerts different effects via different mechanism on endothelium-dependent responses depending on the dose and duration of exposure. Therefore, proper timing and dosing of serelaxin administration in the penile tissue need to be investigated in further studies in diabetic animal models.

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Fig. 1: Study protocol.
Fig. 2: Serelaxin-mediated relaxation relative to the time-control in the CC.
Fig. 3: Effect of hyperglycemia on endothelium-dependent relaxations.
Fig. 4: Effect of serelaxin on NO-mediated relaxations under hyperglycemic conditions.
Fig. 5: Effect of serelaxin on prostacyclin-mediated relaxations under hyperglycemic conditions.

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Acknowledgements

This project was funded by Dokuz Eylül University Scientific Research Projects Coordination Unit (2018.KB.SAG.065).

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Authors and Affiliations

  1. Dokuz Eylul University, Institute of Health Sciences, Izmir, Turkey

    Selin Acar-Sahan

  2. University of Health Sciences Istanbul Kanuni Sultan Süleyman Education and Research Hospital, Medical Pharmacology, Istanbul, Turkey

    Ozge Guner

  3. Dokuz Eylul University, Vocational School of Health Services, Izmir, Turkey

    Mehmet Ates

  4. Izmir Katip Celebi University, Faculty of Medicine, Department of Pharmacology, Izmir, Turkey

    Tijen Kaya-Temiz

  5. Dokuz Eylul University, Faculty of Medicine, Department of Pharmacology, Izmir, Turkey

    Nergiz Durmus

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  1. Selin Acar-Sahan
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  2. Ozge Guner
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Contributions

ND designed the study. SAS and OG conducted the experiments. SAS and ND did the analysis. SAS, ND, TKT and MA interpreted the data and drafted the manuscript. ND obtained the funding and did supervision.

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Correspondence to Nergiz Durmus.

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This study was approved by the Animal Care and Investigational Committee of Dokuz Eylül University (02/2020).

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Acar-Sahan, S., Guner, O., Ates, M. et al. In vitro effect of relaxin in the rat corpus cavernosum under hyperglycemic and normoglycemic conditions. Int J Impot Res 36, 72–77 (2024). https://doi.org/10.1038/s41443-022-00653-6

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