Gas what: NO is not the only answer to sexual function

WOS: 000350546100004PubMed ID: 24661203The ability to get and keep an erection is important to men for several reasons and the inability is known as erectile dysfunction (ED). ED has started to be accepted as an early indicator of systemic endothelial dysfunction and subsequently of cardiovascular diseases. The role of NO in endothelial relaxation and erectile function is well accepted. The discovery of NO as a small signalling gasotransmitter led to the investigation of the role of other endogenously derived gases, carbon monoxide (CO) and hydrogen sulphide (H2S) in physiological and pathophysiological conditions. The role of NO and CO in sexual function and dysfunction has been investigated more extensively and, recently, the involvement of H2S in erectile function has also been confirmed. In this review, we focus on the role of these three sister gasotransmitters in the physiology, pharmacology and pathophysiology of sexual function in man, specifically erectile function. We have also reviewed the role of soluble guanylyl cyclase/cGMP pathway as a common target of these gasotransmitters. Several studies have proposed alternative therapies targeting different mechanisms in addition to PDE-5 inhibition for ED treatment, since some patients do not respond to these drugs. This review highlights complementary and possible coordinated roles for these mediators and treatments targeting these gasotransmitters in erectile function/ED. Linked ArticlesThis article is part of a themed section on Pharmacology of the Gasotransmitters. To view the other articles in this section visitTurkish Academia Young investigator award programmeTurkish Academy of Sciences; TUBA-GebipTurkish Academy of Sciences; Turkish Scientific Research Council TUBITAKTurkiye Bilimsel ve Teknolojik Arastirma Kurumu (TUBITAK) [109S453, 109S432]; EBILTEMEge University; Conselho Nacional de Desenvolvimento Cientifico e Tecnologico; CNPqNational Council for Scientific and Technological Development (CNPq); Fundacao de Amparo a Pesquisa e Inovacao do Estado de Santa Catarina; FAPESC; COST actionEuropean Cooperation in Science and Technology (COST) [BM1005]The authors would like to thank the financial supports by Turkish Academia Young investigator award programme; TUBA-Gebip (to G. Y. A.), Turkish Scientific Research Council TUBITAK for the grant #109S453 and # 109S432 (to G. Y. A.), EBILTEM (to G. Y. A.), Conselho Nacional de Desenvolvimento Cientifico e Tecnologico; CNPq (to A. E. L.) and Fundacao de Amparo a Pesquisa e Inovacao do Estado de Santa Catarina; FAPESC (to A. E. L.) and the COST action BM1005 (ENOG: European Network on Gasotransmitters)

The anti-angiogenic potential of (±) gossypol in comparison to suramin

Cotton, a staple fiber that grows around the seeds of the cotton plants (Gossypium), is produced throughout the world, and its by products, such as cotton fibers, cotton-seed oil, and cottonseed proteins, have a variety of applications. Cotton-seed contains gossypol, a natural phenol compound. (±)-Gossypol is a yellowish polyphenol that is derived from different parts of the cotton plant and contains potent anticancer properties. Tumor growth and metastasis are mainly related to angiogenesis; therefore, anti-angiogenic therapy targets the new blood vessels that provide oxygen and nutrients to actively proliferating tumor cells. The aim of the present study was to evaluate the anti-angiogenic potential of (±)-gossypol in vitro. (±)-Gossypol has anti-proliferative effects on cancer cell lines; however, its anti-angiogenic effects on normal cells have not been studied. Anti-proliferative activities of gossypol assessed using 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay, anti-angiogenic activities using tube formation assay, and cell migration inhibition capability using a wound-healing assay on human umbilical vein endothelial cells (HUVECs) were revealed. (±)-Gossypol displayed the following potent anti-angiogenic activities in vitro: it inhibited the cell viability of HUVECs, it inhibited the migration of HUVECs, and disrupted endothelial tube formation in a dose-dependent manner. In addition, the anti-angiogenic effects of (±)-gossypol were investigated in ovo in a model using a chick chorioallantoic membrane (CAM). Decreases in capillary density were assessed and scored. (±)-Gossypol showed dose-dependent anti-angiogenic effects on CAM. These findings suggest that (±)-gossypol can be used as a new anti-angiogenic agent. © 2018, Springer Nature B.V.2011-FEN-006Acknowledgements This study was supported by the Scientific Research Council of Ege University (Project No: 2011-FEN-006). -

Diverse effects of taurine on vascular response and inflammation in GSH depletion model in rabbits

WOS: 000376904300025PubMed ID: 27097960OBJECTIVE: A reduction in GSH and an increase in free radicals are observed in inflammatory diseases, indicating oxidative stress. Taurine protects cells from the cytotoxic effects of inflammation. There have been limited studies to date evaluating the effect of taurine in oxidative stress-induced vascular dysfunction and its role in vascular inflammatory diseases. Therefore, we aimed to investigate the effect of taurine on the regulation of vascular tonus and vascular inflammatory markers in rabbit aortae and carotid arteries in oxidative stress-induced by GSH depletion. MATERIALS AND METHODS: Rabbits were treated subcutaneously with buthionine sulfoximine (BSO), GSH-depleting compound and/or taurine. Cumulative concentration-response curves for acetylcholine (ACh), phenylephrine and 5-hydroxytriptamine (5-HT) were constructed with or without N-omega-nitro-L-arginine (LNA) in the carotid artery and aorta rings. Immunohistochemical staining was performed for TNF-alpha and IL-1 beta. RESULTS: BSO increased ACh-induced NOdependent relaxations, phenylephrine-induced contractions in the carotid artery and 5-HT induced-contractions in both the carotid artery and the aorta. BSO decreased EDHF dependent relaxations only in the aorta. ACh-induced NO-dependent relaxations and augmented contractions were normalized by taurine. BSO increased TNF-alpha expressions in both carotid arteries and aortas, which were reversed by taurine. The BSO-induced increase in IL-1 beta was reversed by taurine only in aortae. CONCLUSIONS: Treatment with BSO resulted in vascular reactivity changes and increased immunostaining of TNF-alpha in mainly carotid arteries in this model of oxidative stress. The effect of taurine on BSO-induced vascular reactivity changes varied depending on the vessel. The inhibition of the increase in TNF-alpha expression by taurine in both carotid arteries and aortae supports the proposal that taurine has a beneficial effect in the treatment of inflammatory diseases such as atherosclerosis.Ege University Scientific Research FundEge University [06ECZ008, 08ECZ019]This work was supported by grants from the Ege University Scientific Research Fund (06ECZ008, ZK) and (08ECZ019, ZK)

Diverse effects of taurine on vascular response and inflammation in GSH depletion model in rabbits

WOS: 000376904300025PubMed ID: 27097960OBJECTIVE: A reduction in GSH and an increase in free radicals are observed in inflammatory diseases, indicating oxidative stress. Taurine protects cells from the cytotoxic effects of inflammation. There have been limited studies to date evaluating the effect of taurine in oxidative stress-induced vascular dysfunction and its role in vascular inflammatory diseases. Therefore, we aimed to investigate the effect of taurine on the regulation of vascular tonus and vascular inflammatory markers in rabbit aortae and carotid arteries in oxidative stress-induced by GSH depletion. MATERIALS AND METHODS: Rabbits were treated subcutaneously with buthionine sulfoximine (BSO), GSH-depleting compound and/or taurine. Cumulative concentration-response curves for acetylcholine (ACh), phenylephrine and 5-hydroxytriptamine (5-HT) were constructed with or without N-omega-nitro-L-arginine (LNA) in the carotid artery and aorta rings. Immunohistochemical staining was performed for TNF-alpha and IL-1 beta. RESULTS: BSO increased ACh-induced NOdependent relaxations, phenylephrine-induced contractions in the carotid artery and 5-HT induced-contractions in both the carotid artery and the aorta. BSO decreased EDHF dependent relaxations only in the aorta. ACh-induced NO-dependent relaxations and augmented contractions were normalized by taurine. BSO increased TNF-alpha expressions in both carotid arteries and aortas, which were reversed by taurine. The BSO-induced increase in IL-1 beta was reversed by taurine only in aortae. CONCLUSIONS: Treatment with BSO resulted in vascular reactivity changes and increased immunostaining of TNF-alpha in mainly carotid arteries in this model of oxidative stress. The effect of taurine on BSO-induced vascular reactivity changes varied depending on the vessel. The inhibition of the increase in TNF-alpha expression by taurine in both carotid arteries and aortae supports the proposal that taurine has a beneficial effect in the treatment of inflammatory diseases such as atherosclerosis.Ege University Scientific Research FundEge University [06ECZ008, 08ECZ019]This work was supported by grants from the Ege University Scientific Research Fund (06ECZ008, ZK) and (08ECZ019, ZK)

Resveratrol Stimulates Hydrogen Sulfide (H2S) Formation to Relax Murine Corpus Cavernosum

PubMed ID: 26437677Introduction: 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 (H2S) is a potent vasodilator and neuromodulator generated in corpus cavernosum. Aims: We investigated whether RVT caused the relaxation of mice corpus cavernosum (MCC) through H2S. Methods: H2S 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 N?-Nitro-L-arginine (L-NNA, 0.1mM) or H2S inhibitor aminooxyacetic acid (AOAA, 2mM) which inhibits both cystathionine-ß-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. Results: Exposure 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. Conclusions: These 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, Ozzayim O, Erac Y, and Ahmed A. Resveratrol stimulates hydrogen sulfide (H2S) formation to relax murine corpus cavernosum. © 2015 International Society for Sexual Medicine.National Council for Scientific Research: 109s453, 114s448 European Cooperation in Science and Technology: BM1005The authors would like to thank the financial support by Turkish Scientific Research Council TUBITAK for the grant #114s448 and #109s453 as project involved in COST action BM1005 (European Network on Gasotransmitters) as well as Turkish Academia Young investigator award program; TUBA-Gebip (to G. Y. A.). We also noted that some equipment in FABAL-pharmaceutical research laboratory of Ege University Faculty of Pharmacy has been used in this study. -

Fluvastatin restores endothelial dysfunction caused by collar in rabbit carotid artery

32nd Congress of the Federation-of-European-Biochemical-Societies (FEBS) -- JUL 07-12, 2007 -- Vienna, AUSTRIAWOS: 000253283800967Federat European Biochem So

The role of resistin on metabolic syndrome-induced erectile dysfunction and the possible therapeutic effect of Boldine

PubMed: 326094302-s2.0-85089007279Background: Resistin is known as a potential mediator of obesity-associated insulin resistance. The high resistin level disrupts nitric oxide (NO)-mediated relaxation which is also important in erectile function. An antioxidant alkaloid, Boldine, is known as anti-diabetic and protects endothelial functions. Objectives: We aimed to investigate resistin expression in penile tissue in the presence of insulin resistance (IR) and the effect of Boldine treatment on erectile functions in the metabolic syndrome (MetS) rat model. Materials and methods: Wistar rats were randomly divided into three groups: Control, MetS, and boldine treated MetS group. MetS parameters were assessed by serum triglycerides (TG), uric acid (UA), glucose, insulin levels, HOMA index, and waist circumference (WC)/tibia length (TL) ratio. To evaluate erectile functions, intracavernous pressure (ICP)/mean arterial pressure (MAP) ratio was performed during cavernous nerve stimulation. Protein expressions of resistin, endothelial nitric oxide synthase (eNOS), p(S1177) eNOS, and insulin receptor-? were evaluated by Western blotting. Results: TG, glucose, insulin levels, weight, WC/TL ratio, HOMA index and resistin expression in penile tissue were significantly increased and ICP/MAP values, and p (S1177) eNOS expression in penile tissue were decreased in MetS group. Boldine treatment enhanced ICP/MAP values, insulin receptor-? and p(S1177) eNOS expressions compared with the MetS group. Discussion and Conclusion: MetS caused a deterioration in erectile function accompanied by an increase in resistin expression and a reduction in eNOS enzyme activation in the rat penile tissues. Boldine treatment resulted in an improvement in erectile function, independent of resistin expression. © 2020 American Society of Andrology and European Academy of AndrologyTürkiye Bilimsel ve Teknolojik Araştirma Kurumu, TÜBITAK: 114S792This study was supported by the Scientific and Technological Research Council of Turkey (114S792)