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Hydrogen sulfide-induced relaxation of the bladder is attenuated in spontaneously hypertensive rats

  • Urology - Original Paper
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Abstract

Purpose

To compare hydrogen sulfide (H2S)-induced relaxation on the bladder between normotensive and spontaneously hypertensive rat (SHR), we evaluated the effects of H2S donors (GYY4137 and NaHS) on the micturition reflex and on the contractility of bladder tissues. We also investigated the content of H2S and the expression levels of enzymes related to H2S biosynthesis [cystathionine β-synthase (CBS), 3-mercaptopyruvate sulfurtransferase (MPST), and cysteine aminotransferase (CAT)] in the bladder.

Methods

Eighteen-week-old male normotensive Wistar rats and SHRs were used. Under urethane anesthesia, the effects of intravesically instilled GYY4137 (10−8, 10−7 and 10−6 M) on the micturition reflex were evaluated by cystometry. The effects of NaHS (1 × 10−8–3 × 10−4 M) were evaluated on carbachol (10−5 M)-induced pre-contracted bladder strips. Tissue H2S content was measured by the methylene blue method. The expression levels of these enzymes were investigated by Western blot.

Results

GYY4137 significantly prolonged intercontraction intervals in Wistar rats, but not in SHRs. NaHS-induced relaxation on pre-contracted bladder strips was significantly attenuated in SHRs compared with Wistar rats. The H2S content in the bladder of SHRs was significantly higher than that of Wistar rats. CBS, MPST and CAT were detected in the bladder of Wistar rats and SHRs. The expression levels of MPST in the SHR bladder were significantly higher than those in the Wistar rat bladder.

Conclusion

H2S-induced bladder relaxation in SHRs is impaired, thereby resulting in a compensatory increase of the H2S content in the SHR bladder.

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Abbreviations

BBF:

Bladder blood flow

BBR:

Bladder body weight ratio

BL-D:

Bladder dome

BL-T:

Bladder trigone

CAT:

Cysteine aminotransferase

CBS:

Cystathionine β-synthase

CSE:

Cystathionine γ-lyase

DO:

Detrusor overactivity

IACUC:

Institutional Animal Care and Use Committees

ICI:

Intercontraction intervals

KATP channel:

ATP-sensitive potassium channel

LUTS:

Lower urinary tract symptoms

MPST:

3-Mercaptopyruvate sulfurtransferase

MVP:

Maximal voiding pressure

NO:

Nitric oxide

OAB:

Overactive bladder

SHR:

Spontaneously hypertensive rat

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Acknowledgements

This work was supported in part by a Grant-in-Aid for Challenging Exploratory Research (No. 15K15583 to M.S.) from the Japan Society for the Promotion of Science, and GSK Japan Research Grant 2017.

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Authors and Affiliations

  1. Department of Pharmacology, Kochi Medical School, Kochi University, Nankoku, Kochi, 783-8505, Japan

    Suo Zou, Takahiro Shimizu, Masaki Yamamoto, Shogo Shimizu, Youichirou Higashi & Motoaki Saito

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  1. Suo Zou
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  2. Takahiro Shimizu
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  3. Masaki Yamamoto
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  4. Shogo Shimizu
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Correspondence to Takahiro Shimizu.

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Zou, S., Shimizu, T., Yamamoto, M. et al. Hydrogen sulfide-induced relaxation of the bladder is attenuated in spontaneously hypertensive rats. Int Urol Nephrol 51, 1507–1515 (2019). https://doi.org/10.1007/s11255-019-02222-1

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