Resveratrol Stimulates Hydrogen Sulfide (H<sub>2</sub>S) Formation to Relax Murine Corpus Cavernosum


YETİK ANACAK G. Y., Dereli M. V., Sevin G., Ozzayim O., Erac Y., Ahmed A.

JOURNAL OF SEXUAL MEDICINE, cilt.12, sa.10, ss.2004-2012, 2015 (SCI-Expanded) identifier identifier identifier identifier

  • Yayın Türü: Makale / Tam Makale
  • Cilt numarası: 12 Sayı: 10
  • Basım Tarihi: 2015
  • Doi Numarası: 10.1111/jsm.12993
  • Dergi Adı: JOURNAL OF SEXUAL MEDICINE
  • Derginin Tarandığı İndeksler: Science Citation Index Expanded (SCI-EXPANDED), Scopus
  • Sayfa Sayıları: ss.2004-2012
  • Acıbadem Mehmet Ali Aydınlar Üniversitesi Adresli: Hayır

Özet

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. MethodsH(2)S 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 N-Nitro-L-arginine (L-NNA, 0.1mM) or H2S inhibitor aminooxyacetic acid (AOAA, 2mM) which inhibits both cystathionine--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 (0.1mM, 30min) 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, Ozzaym O, Erac Y, and Ahmed A. Resveratrol stimulates hydrogen sulfide (H2S) formation to relax murine corpus cavernosum. J Sex Med 2015;12:2004-2012.