Age-related differences in responses to hydrogen sulfide in the bladder of spontaneously hypertensive rats

Abstract

We have confirmed that hydrogen sulfide (H 2 S) is a possible relaxation factor in the rat bladder, and H 2 S-induced bladder relaxation is impaired in 18-week-old (18W) spontaneously hypertensive rats (SHRs), which show bladder dysfunctions. We compared effects of NaHS and GYY4137 (H 2 S donors) on bladder contractility and micturition reflex, and H 2 S contents and expression of enzymes related to H 2 S biosynthesis (CBS, MPST and CAT) in the bladder between 12W and 18W male SHRs. Effects of NaHS (1×10-8 to 3×10-4 M) were evaluated on carbachol (10-5 M)induced pre-contracted bladder strips. Under urethane-anesthesia, effects of intravesically instilled GYY4137 (10-8 to 10-6 M) on the rat micturition reflex were examined. The H 2 S contents and expression of CBS, MPST and CAT were measured by methylene blue method and western botting. Compared to 12W SHRs, NaHS-induced maximal relaxation of bladder strips was significantly decreased, GYY4137-induced intercontraction intervals prolongation was attenuated, the bladder H 2 S content and expression level of CBS, MPST and CAT in the bladder dome was higher in 18W SHRs. These results indicate that H 2 S-induced bladder relaxation in SHRs is impaired time-dependently, suggesting that early intervention in SHRs with H 2 S donors may prevent the development of hypertension-mediated bladder dysfunctions.

Editorial Comment to Age‐related differences in responses to hydrogen sulfide in the bladder of spontaneously hypertensive rats

“…Furthermore, according to the findings of cystometry before and after administration of GYY4137 into the bladder, the prolonged intercontraction interval, which was observed in normal hypertensive rats, was abolished in the SHR. In this study, GYY4137 administration extended the intercontraction interval only in SHR at the age of 12 weeks, and not in 18‐week‐old SHR 5 . From the aforementioned findings, the relaxation of the bladder smooth muscles and the suppression of the urination reflex caused by H 2 S are weakened in an age‐dependent manner in SHR, conceivably making it one of the factors of bladder dysfunction caused by hypertension.…”

“…In this study, GYY4137 administration extended the intercontraction interval only in SHR at the age of 12 weeks, and not in 18-week-old SHR. 5 From the aforementioned findings, the relaxation of the bladder smooth muscles and the suppression of the urination reflex caused by H 2 S are weakened in an age-dependent manner in SHR, conceivably making it one of the factors of bladder dysfunction caused by hypertension. Therefore, the intervention of H 2 S in an early stage of hypertension might suppress the progression of bladder dysfunction caused by lasting hypertension.…”