Resveratrol Stimulates Hydrogen Sulfide (H2S) Formation to Relax Murine Corpus Cavernosum |
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| Institution: | 1. Department of PharmacologyFaculty of PharmacyEge UniversityIzmirTurkey;2. Aston Medical Research InstituteAston Medical SchoolAston UniversityBirminghamUK;1. Institute of Normal and Pathological Physiology SAS, Sienkiewiczova 1, 81371 Bratislava, Slovakia;2. Institute of Molecular Physiology and Genetics SAS, Vlarska 5, 83334 Bratislava, Slovakia;3. Center for Molecular Medicine SAS, Vlarska 7, 83101 Bratislava, Slovakia;4. Institute for Biological Research “Siniša Stanković”, University of Belgrade, Blvd Despota Stefana 142, Belgrade, Serbia;5. Faculty of Chemical and Food Technology, Slovak University of Technology, Radlinskeho 9, 81237 Bratislava, Slovakia;6. Department of Molecular Immunology and Toxicology, National Institute of Oncology, Ráth György utca 7-9, Budapest, 1122 Hungary;7. Faculty of Pharmacy, Comenius University, Odbojarov 10, 83232 Bratislava, Slovakia;8. Clinical & Experimental Sciences, Faculty of Medicine, Southampton General Hospital, University of Southampton, Tremona Road, Southampton, UK |
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| Abstract: | IntroductionResveratrol (RVT) found in red wine protects against erectile dysfunction and relaxes penile tissue (corpus cavernosum) via a nitric oxide (NO) independent pathway. However, the mechanism remains to be elucidated. Hydrogen sulfide (H2S) is a potent vasodilator and neuromodulator generated in corpus cavernosum.AimsWe investigated whether RVT caused the relaxation of mice corpus cavernosum (MCC) through H2S.MethodsH2S formation is measured by methylene blue assay and vascular reactivity experiments have been performed by DMT strip myograph in CD1 MCC strips.Main Outcome MeasuresEndothelial NO synthase (eNOS) inhibitor Nω-Nitro-L-arginine (L-NNA, 0.1 mM) or H2S inhibitor aminooxyacetic acid (AOAA, 2 mM) which inhibits both cystathionine-β-synthase (CBS) and cystathionine-gamma-lyase (CSE) enzyme or combination of AOAA with PAG (CSE inhibitor) has been used in the presence/absence of RVT (0.1 mM, 30 min) to elucidate the role of NO or H2S pathways on the effects of RVT in MCC. Concentration-dependent relaxations to RVT, L-cysteine, sodium hydrogen sulfide (NaHS) and acetylcholine (ACh) were studied.ResultsExposure of murine corpus cavernosum to RVT increased both basal and L-cysteine-stimulated H2S formation. Both of these effects were reversed by AOAA but not by L-NNA. RVT caused concentration-dependent relaxation of MCC and that RVT-induced relaxation was significantly inhibited by AOAA or AOAA + PAG but not by L-NNA. L-cysteine caused concentration-dependent relaxations, which are inhibited by AOAA or AOAA + PAG significantly. Incubation of MCC with RVT significantly increased L-cysteine-induced relaxation, and this effect was inhibited by AOAA + PAG. However, RVT did not alter the effect of exogenous H2S (NaHS) or ACh-induced relaxations.ConclusionsThese results demonstrate that RVT-induced relaxation is at least partly dependent on H2S formation and acts independent of eNOS pathway. In phosphodiesterase 5 inhibitor (PDE-5i) nonresponder population, combination therapy with RVT may reverse erectile dysfunction via stimulating endogenous H2S formation. Yetik-Anacak G, Dereli MV, Sevin G, Ozzayım O, Erac Y, and Ahmed A. Resveratrol stimulates hydrogen sulfide (H2S) formation to relax murine corpus cavernosum. |
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