Skip to main content
SpringerLink
Log in
Book cover

Chemistry, Biochemistry and Pharmacology of Hydrogen Sulfide pp 111–136Cite as

Hydrogen Sulfide and Urogenital Tract

  • Chapter

Part of the book series: Handbook of Experimental Pharmacology ((HEP,volume 230))

Abstract

In this chapter the role played by H2S in the physiopathology of urogenital tract revising animal and human data available in the current relevant literature is discussed. H2S pathway has been demonstrated to be involved in the mechanism underlying penile erection in human and experimental animal. Both cystathionine-β synthase (CBS) and cystathionine-γ lyase (CSE) are expressed in the human corpus cavernosum and exogenous H2S relaxes isolated human corpus cavernosum strips in an endothelium-independent manner. Hydrogen sulfide pathway also accounts for the direct vasodilatory effect operated by testosterone on isolated vessels. Convincing evidence suggests that H2S can influence the cGMP pathway by inhibiting the phosphodiesterase 5 (PDE-5) activity. All these findings taken together suggest an important role for the H2S pathway in human corpus cavernosum homeostasis. However, H2S effect is not confined to human corpus cavernosum but also plays an important role in human bladder. Human bladder expresses mainly CBS and generates in vitro detectable amount of H2S. In addition the bladder relaxant effect of the PDE-5 inhibitor sildenafil involves H2S as mediator.

In conclusion the H2S pathway is not only involved in penile erection but also plays a role in bladder homeostasis. In addition the finding that it involved in the mechanism of action of PDE-5 inhibitors strongly suggests that modulation of this pathway can represent a therapeutic target for the treatment of erectile dysfunction and bladder diseases.

This is a preview of subscription content, log in via an institution.

Chapter
USD   29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD   169.00
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Hardcover Book
USD   219.99
Price excludes VAT (USA)
  • Durable hardcover edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Learn about institutional subscriptions

References

  • Abe K, Kimura H (1996) The possible role of hydrogen sulfide as an endogenous neuromodulator. J Neurosci 16:1066–1071

    CAS  PubMed  Google Scholar 

  • Abrams P, Cardozo L, Fall M, Griffiths D, Rosier P, Ulmsten U, van Kerrebroeck P, Victor A, Wein A (2002) The standardization of terminology of lower urinary tract function: report from the Standardisation Sub-committee of the International Continence Society. Neurourol Urodyn 21:167–178

    Article  PubMed  Google Scholar 

  • Altaany Z, Ju Y, Yang G, Wang R (2014) The coordination of S-sulfhydration, S-nitrosylation, and phosphorylation of endothelial nitric oxide synthase by hydrogen sulfide. Sci Signal 7:ra87

    Article  PubMed  Google Scholar 

  • Andersson KE (1992) Clinical pharmacology of potassium channel openers. Pharmacol Toxicol 70:244–254

    Article  CAS  PubMed  Google Scholar 

  • Andersson KE (1993) Pharmacology of lower urinary tract smooth muscles and penile erectile tissues. Pharmacol Rev 45:253–308

    Google Scholar 

  • Andersson KE, Arner A (2004) Urinary bladder contraction and relaxation: physiology and pathophysiology. Physiol Rev 84:935–986

    Article  CAS  PubMed  Google Scholar 

  • Andrade EL, Ferreira J, André E, Calixto JB (2006) Contractile mechanisms coupled to TRPA1 receptor activation in rat urinary bladder. Biochem Pharmacol 72:104–114

    Article  CAS  PubMed  Google Scholar 

  • Angulo J, Cuevas P, Fernández A, Gabancho S, Allona A, Martín-Morales A, Moncada I, Videla S, Sáenz de Tejada I (2003) Diabetes impairs endothelium-dependent relaxation of human penile vascular tissues mediated by NO and EDHF. Biochem Biophys Res Commun 312:1202–1208

    Article  CAS  PubMed  Google Scholar 

  • Aversa A, Isidori AM, De Martino MU, Caprio M, Fabbrini E, Rocchietti-March M, Frajese G, Fabbri A (2000) Androgens and penile erection: evidence for a direct relationship between free testosterone and cavernous vasodilation in men with erectile dysfunction. Clin Endocrinol (Oxf) 53:517–522

    Article  CAS  Google Scholar 

  • Bautista DM, Movahed P, Hinman A, Axelsson HE, Sterner O, Högestätt ED, Julius D, Jordt SE, Zygmunt PM (2005) Pungent products from garlic activate the sensory ion channel TRPA1. Proc Natl Acad Sci USA 102:12248–12252

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Becker AJ, Uckert S, Stief CG, Truss MC, Machtens S, Scheller F, Knapp WH, Hartmann U, Jonas U (2000) Cavernous and systemic testosterone levels in different phases of human penile erection. Urology 56:125–129

    Article  CAS  PubMed  Google Scholar 

  • Becker AJ, Uckert S, Stief CG, Scheller F, Knapp WH, Hartmann U, Jonas U (2001) Cavernous and systemic testosterone plasma levels during different penile conditions in healthy males and patients with erectile dysfunction. Urology 58:435–440

    Article  CAS  PubMed  Google Scholar 

  • Bonev AD, Nelson MT (1993) ATP-sensitive potassium channels in smooth muscle cells from guinea pig urinary bladder. Am J Physiol Cell Physiol 264:C1190–C1200

    CAS  Google Scholar 

  • Brading AF (2006) Spontaneous activity of lower urinary tract smooth muscles: correlation between ion channels and tissue function. J Physiol 570:13–22

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Brancaleone V, Vellecco V, Matassa DS, d’Emmanuele di Villa Bianca R, Sorrentino R, Ianaro A, Bucci M, Esposito F, Cirino G (2014) Crucial role of androgen receptor in vascular H2S biosynthesis induced by testosterone. Br J Pharmacol 172(6):1505–1515

    Article  PubMed  Google Scholar 

  • Brunner H, Cockcroft JR, Deanfield J, Donald A, Ferrannini E, Halcox J, Kiowski W, Lüscher TF, Mancia G, Natali A, Oliver JJ, Pessina AC, Rizzoni D, Rossi GP, Salvetti A, Spieker LE, Taddei S, Webb DJ, Working Group on Endothelins and Endothelial Factors of the European Society of Hypertension (2005) Endothelial function and dysfunction. Part II: association with cardiovascular risk factors and diseases. A statement by the working group on endothelins and endothelial factors of the european society of hypertension. J Hypertens 23:233–246

    Article  CAS  PubMed  Google Scholar 

  • Bucci M, Mirone V, Di Lorenzo A, Vellecco V, Roviezzo F, Brancaleone V, Imbimbo C, Cirino G (2009) Hydrogen sulphide is involved in testosterone vascular effect. Eur Urol 56:378–383

    Article  CAS  PubMed  Google Scholar 

  • Bucci M, Papapetropoulos A, Vellecco V, Zhou Z, Pyriochou A, Roussos C, Roviezzo F, Brancaleone V, Cirino G (2010) Hydrogen sulfide is an endogenous inhibitor of phosphodiesterase activity. Arterioscler Thromb Vasc Biol 30:1998–2004

    Article  CAS  PubMed  Google Scholar 

  • Buckner SA, Milicic I, Daza A, Davis-Taber R, Scott VE, Sullivan JP, Brioni JD (2000) Pharmacological and molecular analysis of ATP-sensitive K channels in the pig and human detrusor. Eur J Pharmacol 400:287–295

    Article  CAS  PubMed  Google Scholar 

  • Busse R, Edwards G, Félétou M, Fleming I, Vanhoutte PM, Weston AH (2002) EDHF: bringing the concepts together. Trends Pharmacol Sci 23:374–380

    Article  CAS  PubMed  Google Scholar 

  • Cai WJ, Wang MJ, Moore PK, Jin HM, Yao T, Zhu YC (2007) The novel proangiogenic effect of hydrogen sulfide is dependent on Akt phosphorylation. Cardiovasc Res 76:29–40

    Article  CAS  PubMed  Google Scholar 

  • Christ GJ, Hodges S (2006) Molecular mechanisms of detrusor and corporal myocyte contraction: identifying targets for pharmacotherapy of bladder and erectile dysfunction. Br J Pharmacol 147(Suppl 2):S41–S55

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Christ GJ, Brink PR, Melman A, Spray DC (1993) The role of gap junctions and ion channels in the modulation of electrical and chemical signals in human corpus cavernosum smooth muscle. Int J Impot Res 5:77–96

    CAS  PubMed  Google Scholar 

  • Cirino G, Fusco F, Imbimbo C, Mirone V (2006) Pharmacology of erectile dysfunction in man. Pharmacol Ther 111:400–423

    Article  CAS  PubMed  Google Scholar 

  • Coletta C, Papapetropoulos A, Erdelyi K, Olah G, Módis K, Panopoulos P, Asimakopoulou A, Gerö D, Sharina I, Martin E, Szabo C (2012) Hydrogen sulfide and nitric oxide are mutually dependent in the regulation of angiogenesis and endothelium-dependent vasorelaxation. Proc Natl Acad Sci USA 109:9161–9166

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • d’Emmanuele di Villa Bianca R, Sorrentino R, Maffia P, Mirone V, Imbimbo C, Fusco F, De Palma R, Ignarro LJ, Cirino G (2009) Hydrogen sulfide as a mediator of human corpus cavernosum smooth-muscle relaxation. Proc Natl Acad Sci USA 106:4513–4518

    Article  PubMed Central  PubMed  Google Scholar 

  • d’Emmanuele di Villa Bianca R, Sorrentino R, Coletta C, Mitidieri E, Rossi A, Vellecco V et al (2011) Hydrogen sulfide-induced dual vascular effect involves arachidonic acid cascade in rat mesenteric arterial bed. J Pharmacol Exp Ther 337:59–64

    Article  PubMed  Google Scholar 

  • de Groat WC, Yoshimura N (2001) Pharmacology of the lower urinary tract. Annu Rev Pharmacol Toxicol 41:691–721

    Article  PubMed  Google Scholar 

  • Dikmen A, d’Emmanuele di Villa Bianca R, Mitidieri E, Donnarumma E, Sevin G, Cirino G, Sorrentino R, Yetik-Anacak G (2013) New mechanism for the beneficial effect of sildenafil on erectile function: H2S. Nitric Oxide 31:S38

    Article  Google Scholar 

  • Dombkowski RA, Doellman MM, Head SK, Olson KR (2006) Hydrogen sulfide mediates hypoxia-induced relaxation of trout urinary bladder smooth muscle. J Exp Biol 209:3234–3340

    Article  PubMed  Google Scholar 

  • Dong JY, Zhang YH, Qin LQ (2011) Erectile dysfunction and risk of cardiovascular disease: meta-analysis of prospective cohort studies. J Am Coll Cardiol 58:1378–1385

    Article  PubMed  Google Scholar 

  • Fernandes VS, Ribeiro AS, Barahona MV, Orensanz LM, Martínez-Sáenz A, Recio P, Martínez AC, Bustamante S, Carballido J, García-Sacristán A, Prieto D, Hernández M (2013a) Hydrogen sulfide mediated inhibitory neurotransmission to the pig bladder neck: role of KATP channels, sensory nerves and calcium signaling. J Urol 190:746–756

    Article  CAS  PubMed  Google Scholar 

  • Fernandes VS, Ribeiro AS, Martínez MP, Orensanz LM, Barahona MV, Martínez-Sáenz A, Recio P, Benedito S, Bustamante S, Carballido J, García-Sacristán A, Prieto D, Hernández M (2013b) Endogenous hydrogen sulfide has a powerful role in inhibitory neurotransmission to the pig bladder neck. J Urol 189:1567–1573

    Article  CAS  PubMed  Google Scholar 

  • Fusco F, d’Emmanuele di Villa Bianca RD, Mitidieri E, Cirino G, Sorrentino R, Mirone V (2012) Sildenafil effect on the human bladder involves the L-cysteine/hydrogen sulfide pathway: a novel mechanism of action of phosphodiesterase type 5 inhibitors. Eur Urol 62:1174–1180

    Article  CAS  PubMed  Google Scholar 

  • Gai JW, Wahafu W, Guo H, Liu M, Wang XC, Xiao YX, Zhang L, Xin ZC, Jin J (2013) Further evidence of endogenous hydrogen sulphide as a mediator of relaxation in human and rat bladder. Asian J Androl 15:692–696

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Gandaglia G, Briganti A, Jackson G, Kloner RA, Montorsi F, Montorsi P, Vlachopoulos C (2014) A systematic review of the association between erectile dysfunction and cardiovascular disease. Eur Urol 65:968–978

    Article  PubMed  Google Scholar 

  • Geng B, Cui Y, Zhao J, Yu F, Zhu Y, Xu G, Zhang Z, Tang C, Du J (2007) Hydrogen sulfide downregulates the aortic L-arginine/nitric oxide pathway in rats. Am J Physiol Regul Integr Comp Physiol 293:R1608–R1618

    Article  CAS  PubMed  Google Scholar 

  • Ghasemi M, Dehpour AR, Moore KP, Mani AR (2012) Role of endogenous hydrogen sulfide in neurogenic relaxation of rat corpus cavernosum. Biochem Pharmacol 83:1261–1268

    Article  CAS  PubMed  Google Scholar 

  • Goldstein I, Young JM, Fischer J, Bangerter K, Segerson T, Taylor T (2003) Vardenafil a new phosphodiesterase type 5 inhibitor, in the treatment of erectile dysfunction in men with diabetes: a multicenter double-blind placebo-controlled fixed-dose study. Diabetes Care 26:777–783

    Article  CAS  PubMed  Google Scholar 

  • Gopalakrishnan M, Shieh CC (2004) Potassium channel subtypes as molecular targets for overactive bladder and other urological disorders. Expert Opin Ther Targets 8:437–458

    Article  CAS  PubMed  Google Scholar 

  • Gratzke C, Streng T, Waldkirch E, Sigl K, Stief C, Andersson KE, Hedlund P (2009) Transient receptor potential A1 (TRPA1) activity in the human urethra—evidence for a functional role for TRPA1 in the outflow region. Eur Urol 55:696–704

    Article  CAS  PubMed  Google Scholar 

  • Grgic I, Kaistha BP, Hoyer J, Köhler R (2009) Endothelial Ca + −activated K+ channels in normal and impaired EDHF-dilator responses–relevance to cardiovascular pathologies and drug discovery. Br J Pharmacol 157:509–526

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Guo H, Gai JW, Wang Y, Jin HF, Du JB, Jin J (2012) Characterization of hydrogen sulfide and its synthases, cystathionine β-synthase and cystathionine γ-lyase, in human prostatic tissue and cells. Urology 79:483, e1-5

    Article  PubMed  Google Scholar 

  • Hackett G, Kirby M, Sinclair AJ (2014) Testosterone deficiency, cardiac health, and older men. Int J Endocrinol 2014:143763

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Isidori AM, Buvat J, Corona G, Goldstein I, Jannini EA, Lenzi A, Porst H, Salonia A, Traish AM, Maggi M (2014) A critical analysis of the role of testosterone in erectile function: from pathophysiology to treatment-a systematic review. Eur Urol 65:99–112

    Article  CAS  PubMed  Google Scholar 

  • Jacob C, Anwar A, Burkholz T (2008) Perspective on recent developments on sulfur-containing agents and hydrogen sulfide signaling. Planta Med 74:1580–1592

    Article  CAS  PubMed  Google Scholar 

  • Jiang B, Tang G, Cao K, Wu L, Wang R (2010) Molecular mechanism for H(2)S-induced activation of K(ATP) channels. Antioxid Redox Signal 12:1167–1178

    Article  CAS  PubMed  Google Scholar 

  • Kajioka S, Nakayama S, Asano H, Seki N, Naito S, Brading AF (2008) Levcromakalim and MgGDP activate small conductance ATP-sensitive K + channels of K+ channel pore 6.1/sulfonylurea receptor 2A in pig detrusor smooth muscle cells: uncoupling of cAMP signal pathways. J Pharmacol Exp Ther 327:114–123

    Article  CAS  PubMed  Google Scholar 

  • Kardong KV (2005) The urogenital system. In: Vertebrates: compartive anatomy, function, evolution. McGraw Hill Higher Education, New York, pp 577–578 (Chapter 14)

    Google Scholar 

  • Karicheti V, Christ GJ (2001) Physiological roles for K+ channels and gap junctions in urogenital smooth muscle: implications for improved understanding of urogenital function, disease and therapy. Curr Drug Targets 2:1–20

    Article  CAS  PubMed  Google Scholar 

  • Kashfi K (2014) Anti-cancer activity of new designer hydrogen sulfide-donating hybrids. Antioxid Redox Signal 20:831–846

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Kashfi K, Olson KR (2013) Biology and therapeutic potential of hydrogen sulfide and hydrogen sulfide-releasing chimeras. Biochem Pharmacol 85:689–703

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Li J, Li Y, Du Y, Mou K, Sun H, Zang Y, Liu C (2011) Endogenous hydrogen sulfide as a mediator of vas deferens smooth muscle relaxation. Fertil Steril 95:1833–1835

    Article  CAS  PubMed  Google Scholar 

  • Li Y, Zang Y, Fu S, Zhang H, Gao L, Li J (2012) H2S relaxes vas deferens smooth muscle by modulating the large conductance Ca2 + −activated K+ (BKCa) channels via a redox mechanism. J Sex Med 9:2806–2813

    Article  PubMed  Google Scholar 

  • Li L, Fox B, Keeble J, Salto-Tellez M, Winyard PG, Wood ME, Moore PK, Whiteman M (2013) The complex effects of the slow-releasing hydrogen sulfide donor GYY4137 in a model of acute joint inflammation and in human cartilage cells. J Cell Mol Med 17:365–376

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Matsunami M, Miki T, Nishiura K, Hayashi Y, Okawa Y, Nishikawa H, Sekiguchi F, Kubo L, Ozaki T, Tsujiuchi T, Kawabata A (2012) Involvement of the endogenous hydrogen sulfide/Ca(v) 3.2 T-type Ca2+ channel pathway in cystitis-related bladder pain in mice. Br J Pharmacol 167:917–928

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Meng J, Ganesan Adaikan P, Srilatha B (2013) Hydrogen sulfide promotes nitric oxide production in corpus cavernosum by enhancing expression of endothelial nitric oxide synthase. Int J Impot Res 25:86–90

    Article  CAS  PubMed  Google Scholar 

  • Milsom I, Abrams P, Cardozo L, Roberts RG, Thuroff J, Wein AJ (2001) How widespread are the symptoms of an overactive bladder and how are they managed? A population-based prevalence study. BJU Int 87:760–766

    Article  CAS  PubMed  Google Scholar 

  • Mirone V, Sorrentino R, di Villa BR, Imbimbo C, Palmieri A, Fusco F, Tajana G, Cirino G (2000) A standardized procedure for using human corpus cavernosum strips to evaluate drug activity. J Pharmacol Toxicol Methods 44:477–482

    Article  CAS  PubMed  Google Scholar 

  • Munaron L, Avanzato D, Moccia F, Mancardi D (2013) Hydrogen sulfide as a regulator of calcium channels. Cell Calcium 53:77–84

    Article  CAS  PubMed  Google Scholar 

  • Mustafa AK, Sikka G, Gazi SK, Steppan J, Jung SM, Bhunia AK, Barodka VM, Gazi FK, Barrow RK, Wang R, Amzel LM, Berkowitz DE, Snyder SH (2011) Hydrogen sulfide as endothelium-derived hyperpolarizing factor sulfhydrates potassium channels. Circ Res 109:1259–1268

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Nehra A, Jackson G, Miner M, Billups KL, Burnett AL, Buvat J, Carson CC, Cunningham GR, Ganz P, Goldstein I, Guay AT, Hackett G, Kloner RA, Kostis J, Montorsi P, Ramsey M, Rosen R, Sadovsky R, Seftel AD, Shabsigh R, Vlachopoulos C, Wu FC (2012) The Princeton III Consensus recommendations for the management of erectile dysfunction and cardiovascular disease. Mayo Clin Proc 87:766–778

    Article  PubMed Central  PubMed  Google Scholar 

  • Nelson CP, Rainbow RD, Brignell JL, Perry MD, Willets JM, Davies NW, Standen NB, Challiss RA (2011) Principal role of adenylyl cyclase 6 in K+ channel regulation and vasodilator signalling in vascular smooth muscle cells. Cardiovasc Res 91:694–702

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Nilius B, Owsianik G, Voets T, Peters JA (2007) Transient receptor potential cation channels in disease. Physiol Rev 87:165–217

    Article  CAS  PubMed  Google Scholar 

  • Olson KR (2014) Hydrogen sulfide as an oxygen sensor. Antioxid Redox Signal 22(5):377–397

    Article  PubMed  Google Scholar 

  • Patacchini R, Maggi CA, Meli A (1990) Capsaicin-like activity of some natural pungent substances on peripheral endings of visceral primary afferents. Naunyn Schmiedebergs Arch Pharmacol 342:72–77

    Article  CAS  PubMed  Google Scholar 

  • Patacchini R, Santicioli P, Giuliani S, Maggi CA (2004) Hydrogen sulfide (H2S) stimulates capsaicin-sensitive primary afferent neurons in the rat urinary bladder. Br J Pharmacol 142:31–34

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Patacchini R, Santicioli P, Giuliani S, Maggi CA (2005) Pharmacological investigation of hydrogen sulfide (H2S) contractile activity in rat detrusor muscle. Eur J Pharmacol 509:171–177

    Article  CAS  PubMed  Google Scholar 

  • Petkov GV, Heppner TJ, Bonev AD, Herrera GM, Nelson MT (2001) Low levels of KATP channel activation decrease excitability and contractility of urinary bladder. Am J Physiol Regul Integr Comp Physiol 280:R1427–R1433

    CAS  PubMed  Google Scholar 

  • Price DE, Gingell JC, Gepi-Attee S, Warcham K, Yates P, Boolell M (1998) Sildenafil: study of a novel oral treatment for erectile dysfunction in diabetic men. Diabet Med 15:821–825

    Article  CAS  PubMed  Google Scholar 

  • Qiu X, Villalta J, Lin G, Lue TF (2012) Role of hydrogen sulfide in the physiology of penile erection. J Androl 33:529–535

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Rendell MS, Rajfer J, Wicker PA, Smith MD (1999) Sildenafil for treatment of erectile dysfunction in men with diabetes. A randomized controlled trial. JAMA 281:421–426

    Article  CAS  PubMed  Google Scholar 

  • Ruiz Rubio JL, Hernández M, Arcos L, Benedito S, Recio P, García P, García-Sacristán A, Prieto D (2004) Role of ATP-sensitive K+ channels in relaxation of penile resistance arteries. Urology 63:800–805

    Article  PubMed  Google Scholar 

  • Saenz de Tejada I, Anglin G, Knight JR, Emmick JT (2002) Effects of tadalafil on erectile dysfunction in men with diabetes. Diabetes Care 25:2159–2164

    Article  PubMed  Google Scholar 

  • Salloum FN, Chau VQ, Hoke NN, Abbate A, Varma A, Ockaili RA, Toldo S, Kukreja RC (2009) Phosphodiesterase-5 inhibitor, tadalafil, protects against myocardial ischemia/reperfusion through protein-kinase g-dependent generation of hydrogen sulfide. Circulation 120:S31–S36

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Schultheiss D, Badalyan R, Pilatz A, Gabouev AI, Schlote N, Wefer J, von Wasielewski R, Mertsching H, Sohn M, Stief CG, Jonas U (2003) Androgen and estrogen receptors in the human corpus cavernosum penis: immunohistochemical and cell culture results. World J Urol 21:320–324

    Article  CAS  PubMed  Google Scholar 

  • Shieh CC, Feng J, Buckner SA, Brioni JD, Coghlan MJ, Sullivan JP, Gopalakrishnan M (2001) Functional implication of spare ATP-sensitive K+ channels in bladder smooth muscle cells. J Pharmacol Exp Ther 296:669–675

    CAS  PubMed  Google Scholar 

  • Shukla N, Rossoni G, Hotston M, Sparatore A, Del Soldato P, Tazzari V, Persad R, Angelini GD, Jeremy JY (2009) Effect of hydrogen sulphide-donating sildenafil (ACS6) on erectile function and oxidative stress in rabbit isolated corpus cavernosum and in hypertensive rats. BJU Int 103:1522–1529

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Spektor M, Rodriguez R, Rosenbaum RS, Wang HZ, Melman A, Christ GJ (2002) Potassium channels and human corporeal smooth muscle cell tone: further evidence of the physiological relevance of the Maxi-K channel subtype to the regulation of human corporeal smooth muscle tone in vitro. J Urol 167:2628–2635

    Article  CAS  PubMed  Google Scholar 

  • Srilatha B, Adaikan PG, Moore PK (2006) Possible role for the novel gasotransmitter hydrogen sulphide in erectile dysfunction–a pilot study. Eur J Pharmacol 535:280–282

    Article  CAS  PubMed  Google Scholar 

  • Srilatha B, Adaikan PG, Li L, Moore PK (2007) Hydrogen sulphide: a novel endogenous gasotransmitter facilitates erectile function. J Sex Med 4:1304–1311

    Article  CAS  PubMed  Google Scholar 

  • Srilatha B, Hu L, Adaikan GP, Moore PK (2009) Initial characterization of hydrogen sulfide effects in female sexual function. J Sex Med 6:1875–1884

    Article  CAS  PubMed  Google Scholar 

  • Srilatha B, Muthulakshmi P, Adaikan PG, Moore PK (2012) Endogenous hydrogen sulfide insufficiency as a predictor of sexual dysfunction in aging rats. Aging Male 15:153–158

    Article  CAS  PubMed  Google Scholar 

  • Story GM, Peier AM, Reeve AJ, Eid SR, Mosbacher J, Hricik TR, Earley TJ, Hergarden AC, Andersson DA, Hwang SW, McIntyre P, Jegla T, Bevan S, Patapoutian A (2003) ANKTM1, a TRP-like channel expressed in nociceptive neurons, is activated by cold temperatures. Cell 112:819–829

    Article  CAS  PubMed  Google Scholar 

  • Streng T, Axelsson HE, Hedlund P, Andersson DA, Jordt SE, Bevan S, Andersson KE, Högestätt ED, Zygmunt PM (2008) Distribution and function of the hydrogen sulfide-sensitive TRPA1 ion channel in rat urinary bladder. Eur Urol 53:391–399

    Article  CAS  PubMed  Google Scholar 

  • Tang G, Yang G, Jiang B, Ju Y, Wu L, Wang R (2013) H2S is an endothelium-derived hyperpolarizing factor. Antioxid Redox Signal 19:1634–1646

    Article  CAS  PubMed  Google Scholar 

  • Traish AM, Goldstein I, Kim NN (2007) Testosterone and erectile function: from basic research to a new clinical paradigm for managing men with androgen insufficiency and erectile dysfunction. Eur Urol 52:54–70

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Venkateswarlu K, Giraldi A, Zhao W, Wang HZ, Melman A, Spektor M, Christ GJ (2002) Potassium channels and human corporeal smooth muscle cell tone: diabetes and relaxation of human corpus cavernosum smooth muscle by adenosine triphosphate sensitive potassium channel openers. J Urol 168:355–361

    Article  CAS  PubMed  Google Scholar 

  • Vickers MA, Satyanarayana R (2002) Phosphodiesterase type 5 inhibitors for the treatment of erectile dysfunction in patients with diabetes mellitus. Int J Impot Res 14:466–471

    Article  CAS  PubMed  Google Scholar 

  • Wang R (2003) The gasotransmitter role of hydrogen sulfide. Antioxid Redox Signal 5:493–501

    Article  PubMed  Google Scholar 

  • Wang R (2009) Hydrogen sulfide: a new EDRF. Kidney Int 76:700–704

    Article  CAS  PubMed  Google Scholar 

  • Xu S, Liu Z, Liu P (2014) Targeting hydrogen sulfide as a promising therapeutic strategy for atherosclerosis. Int J Cardiol 172:313–317

    Article  PubMed  Google Scholar 

  • Yang J, Wang T, Yang J, Rao K, Zhan Y, Chen RB, Liu Z, Li MC, Zhuan L, Zang GH, Guo SM, Xu H, Wang SG, Liu JH, Ye ZQ (2013) S-allyl cysteine restores erectile function through inhibition of reactive oxygen species generation in diabetic rats. Andrology 1:487–494

    Article  CAS  PubMed  Google Scholar 

  • Yetik-Anacak G, Sorrentino R, Linder AE, Murat N (2014) Gas what: NO is not the only answer to sexual function. Br J Pharmacol 172(6):1434–1454

    Article  PubMed  Google Scholar 

  • Yildiz O, Seyrek M, Irkilata HC, Yildirim I, Tahmaz L, Dayanc M (2009) Testosterone might cause relaxation of human corpus cavernosum by potassium channel opening action. Urology 74:229–232

    Article  PubMed  Google Scholar 

  • Zhao W, Wang R (2002) H2S-induced vasorelaxation and underlying cellular and molecular mechanisms. Am J Physiol Heart Circ Physiol 283:H474–H480

    Article  CAS  PubMed  Google Scholar 

  • Zhao W, Zhang J, Lu Y, Wang R (2001) The vasorelaxant effect of H2S as a novel endogenous gaseous KATP channel opener. EMBO J 20:6008–6016

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Zhao K, Li S, Wu L, Lai C, Yang G (2014) Hydrogen sulfide represses androgen receptor transactivation by targeting at the second zinc finger module. J Biol Chem 289:20824–20835

    Article  CAS  PubMed  Google Scholar 

  • Zuo C, Huang YM, Jiang R, Yang HF, Cheng B, Chen F (2014) Endogenous hydrogen sulfide and androgen deficiency-induced erectile dysfunction in rats. Zhonghua Nan Ke Xue 20:605–612

    CAS  PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Department of Pharmacy, University of Naples, Federico II, Via D. Montesano, 49, Naples, 80131, Italy

    Roberta d’Emmanuele di Villa Bianca, Giuseppe Cirino & Raffaella Sorrentino

Authors
  1. Roberta d’Emmanuele di Villa Bianca
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Giuseppe Cirino
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Raffaella Sorrentino
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Giuseppe Cirino .

Editor information

Editors and Affiliations

  1. National University of Singapore, Singapore, Singapore

    Philip K. Moore

  2. ST. Luke's Campus, University of Exeter Medical School, Exeter, United Kingdom

    Matt Whiteman

Rights and permissions

Reprints and permissions

Copyright information

© 2015 Springer International Publishing Switzerland

About this chapter

Cite this chapter

di Villa Bianca, R.d., Cirino, G., Sorrentino, R. (2015). Hydrogen Sulfide and Urogenital Tract. In: Moore, P., Whiteman, M. (eds) Chemistry, Biochemistry and Pharmacology of Hydrogen Sulfide. Handbook of Experimental Pharmacology, vol 230. Springer, Cham. https://doi.org/10.1007/978-3-319-18144-8_5

Download citation

Publish with us

Policies and ethics

Search

Navigation