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

  • Suo Zou
  • Takahiro ShimizuEmail author
  • Masaki Yamamoto
  • Shogo Shimizu
  • Youichirou Higashi
  • Motoaki Saito
Urology - Original Paper



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.


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.


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.


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


Hydrogen sulfide 3-Mercaptopyruvate sulfurtransferase Spontaneously hypertensive rat Bladder Detrusor overactivity 



Bladder blood flow


Bladder body weight ratio


Bladder dome


Bladder trigone


Cysteine aminotransferase


Cystathionine β-synthase


Cystathionine γ-lyase


Detrusor overactivity


Institutional Animal Care and Use Committees


Intercontraction intervals

KATP channel

ATP-sensitive potassium channel


Lower urinary tract symptoms


3-Mercaptopyruvate sulfurtransferase


Maximal voiding pressure


Nitric oxide


Overactive bladder


Spontaneously hypertensive rat



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.

Compliance with ethical standards

Conflict of interest

None of the contributing authors have any conflict of interest.


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Copyright information

© Springer Nature B.V. 2019

Authors and Affiliations

  1. 1.Department of Pharmacology, Kochi Medical SchoolKochi UniversityNankokuJapan

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