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The Rho-kinase inhibitor Y27632 promotes ureteral relaxation in an in vivo rat model for partial ureteral obstruction

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Abstract

Purpose

Aim of this study was to evaluate the effect of intravenous Y27632 (a ROK inhibitor) on intra-ureteral pressures and on blood pressure in an in vivo rat model for unilateral partial ureteral obstruction (PUO).

Methods

15 Male Sprague Dawley rats were used. Under isofluran anesthesia, saline was continuously infused via polyethylene (PE)-10 catheters inserted in the ureters beneath the kidney pelvis. Left psoas muscle was sutured around the distal left ureter to create a partial obstruction. Carotid artery and femoral vein were cannulated with PE catheters for registration of mean arterial blood pressure (MAP) and for administration of drugs. Left and right ureter pressures and MAP were simultaneously recorded. Y27632 (0.03 and 0.1 mg/kg each n = 6–7) was given intravenously. T-test was used for comparisons.

Results

Spontaneous peristaltic pressure waves were recorded at baseline for both ureters. After the obstruction, Y27632 reduced maximum pressure (MaxP) by 10.5 ± 1.9% (0.03 mg/kg; p = 0.004) and 29.1 ± 4.8% (0.1 mg/kg; p < 0.001), minimum pressure (MinP) by 5.2 ± 2.3% (0.03 mg/kg; p = 0.02) and 12.2 ± 3.4% (0.1 mg/kg; p = 0.009), the area under the curve (AUC) by 7.8 ± 2.4% (0.03 mg/kg; p = 0.008) and 16.5 ± 3.7% (0.1 mg/kg;p = 0.007), the waves amplitude by 23.4 ± 11.3% (0.03 mg/kg; p = 0.098) and 38.7 ± 7.5% (0.1 mg/kg; p < 0.001), with no effect on contraction frequency. During simultaneous recordings from the normal ureter at the investigated doses, Y27632 reduced MaxP, MinP, AUC and waves amplitude by 1–7%. The MAP was reduced by 12.5 ± 5.3% (0.03 mg/kg; p = 0.07) and 15.8 ± 1.8% (0.1 mg/kg; p < 0.001).

Conclusions

Y27632 decreased intra-ureteral pressures of a partially obstructed ureter with limited effect on blood pressure in an animal model of unilateral PUO.

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Abbreviations

Y27632:

[(+)-(R)-trans-4-(1-aminoethyl)-N-(4-pyridil) cyclohexanecarboxamide dihydrochloride monohydrate]

ROK:

Rho-kinase

PE:

Polyethylene

MAP:

Mean arterial blood pressure

mg/kg:

Milligram of the compound administered according to rat body weight

MaxP:

Maximum pressure

MinP:

Minimum pressure

AUC:

Area under the curve

SEM:

Standard error of the mean

PUO:

Partial ureteral obstruction

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Acknowledgements

We are grateful to Fabio Benigni and Arianna Bettiga for technical support. Authors also thank the Urological Research Institute and the Gester Foundation for supporting the research activities.

Author information

Authors and Affiliations

  1. Division of Experimental Oncology/Unit of Urology, URI, IRCCS Ospedale San Raffaele, Milan, Italy

    Luca Villa, Edoardo Pozzi, Eugenio Ventimiglia, Alberto Briganti, Francesco Montorsi & Andrea Salonia

  2. Department of Urology, Ludwig-Maximilians-University of Munich, Munich, Germany

    Philipp Weinhold

  3. Department of Urology, ASST Sette Laghi, Varese, Italy

    Emanuele Zaffuto

  4. Department of Urology, King’s College Hospital, London, UK

    Fabio Castiglione

  5. Department of Molecular Biology and Biochemistry, University of California, Irvine, California, USA

    Roberta Buono

  6. University Vita-Salute San Raffaele, Milan, Italy

    Alberto Briganti, Francesco Montorsi & Andrea Salonia

  7. Department of Clinical Pharmacology, Linköping University, Linköping, Sweden

    Petter Hedlund

  8. Department of Experimental and Clinical Pharmacology, Lund University, Lund, Sweden

    Petter Hedlund

Authors
  1. Luca Villa
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  2. Philipp Weinhold
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Contributions

Conceptualization: LV, PH. Data curation: LV, PW, EZ, FC, EP, EV, RB, AB, FM, AS, PH. Formal analysis: LV. Investigation: LV, AS, PH. Methodology: LV, AS, PH. Project administration: LV, AB, FM, AS, PH. Supervision: AB, FM, AS, PH. Validation: AB, FM, AS, PH. Writing—original draft: LV. Writing—review and editing: AB, FM, AS, PH.

Corresponding author

Correspondence to Luca Villa.

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Research involving human participants and/or animals

The data that support the findings of this study are available from the corresponding author upon reasonable request. Some data may not be made available because of privacy or ethical restrictions. All authors agree to this statement.

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Villa, L., Weinhold, P., Zaffuto, E. et al. The Rho-kinase inhibitor Y27632 promotes ureteral relaxation in an in vivo rat model for partial ureteral obstruction. World J Urol 41, 2541–2547 (2023). https://doi.org/10.1007/s00345-023-04528-3

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  • DOI: https://doi.org/10.1007/s00345-023-04528-3

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