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J Sex Med. 2015 Oct;12(10):2004-12. doi: 10.1111/jsm.12993. Epub 2015 Oct 6.

Resveratrol Stimulates Hydrogen Sulfide (H2 S) Formation to Relax Murine Corpus Cavernosum.

Author information

1
Department of Pharmacology, Faculty of Pharmacy, Ege University, Izmir, Turkey.
2
Aston Medical Research Institute, Aston Medical School, Aston University, Birmingham, UK.

Abstract

INTRODUCTION:

Resveratrol (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 (H2 S) is a potent vasodilator and neuromodulator generated in corpus cavernosum.

AIMS:

We investigated whether RVT caused the relaxation of mice corpus cavernosum (MCC) through H2 S.

METHODS:

H2 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 MEASURES:

Endothelial NO synthase (eNOS) inhibitor Nω-Nitro-L-arginine (L-NNA, 0.1 mM) or H2 S 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 H2 S pathways on the effects of RVT in MCC. Concentration-dependent relaxations to RVT, L-cysteine, sodium hydrogen sulfide (NaHS) and acetylcholine (ACh) were studied.

RESULTS:

Exposure of murine corpus cavernosum to RVT increased both basal and L-cysteine-stimulated H2 S 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 H2 S (NaHS) or ACh-induced relaxations.

CONCLUSIONS:

These results demonstrate that RVT-induced relaxation is at least partly dependent on H2 S 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 H2 S formation.

KEYWORDS:

Corpus Cavernosum; Erectile Dysfunction; Hydrogen Sulfide; Phosphodiesterase 5 Inhibitor; Resveratrol

PMID:
26437677
DOI:
10.1111/jsm.12993
[Indexed for MEDLINE]

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