Investigation of the effect of hydrogen sulfide on intracellular calcium movements in detrusor smooth muscle of ovariectomized rats

Women experience incontinence during menopause, as a result of the decrease in estrogen levels due to aging. Hydrogen sulfide is an endogenous gasotransmitter which has relaxant effect on detrusor smooth muscle and estrogen has role in the expreession of enzymes in its production. Estrogen replacement therapy can be applied to relieve postmenopausal complaints. In this study, intracellular calcium mechanisms and the effect of hydrogen sulfide on these mechanisms on carbachol induced contraction responses of the rat bladder detrusor smooth muscle permeabilized with β-escin in the menopause model induced by ovariectomy and also the possible effects of hormone replacement therapy with 17-ß estradiol on the changing intracellular calcium movements have been studied. On permeabilized detrusor smooth muscle of ovariectomized rats, carbachol induced contraction responses increased and this increase was reversed by estradiol treatment. The increased carbachol contraction responses in ovariectomized rat detrusor were significantly reduced in the presence of the sarcoplasmic reticulum inositol trisphosphate receptor blocker heparin, the calcium channel blocker ryanodine, the Rho kinase inhibitor Y-27632, and the protein kinase C inhibitor GF-109203X. Additionally, the significant reduction in carbachol-induced contraction observed after incubation with the H2S donor NaHS in ovariectomized rat detrusor suggests that the increased carbachol response in menopause may be related to hydrogen sulfide. The findings of this thesis study are important both for the potential use of this experimental model in similar studies and for the development of new drug molecules for the treatment of incontinence.