Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

  • Review
  • Published:

Physiological regulation of penile arteries and veins

International Journal of Impotence Research volume 20, pages 17–29 (2008)Cite this article

Abstract

Recent experimental evidence suggests that arterial insufficiency precedes the structural and functional changes in corpora cavernosa (CC) leading to organic erectile dysfunction (ED). The present review gives an overview of the physiological factors involved in the regulation of penile vasculature. Sympathetic nerves maintain flaccidity and tonically released noradrenaline induces vasoconstriction of both arteries and veins through α1- and α2-postsynaptic receptors and downregulates its own release and that of nitric oxide (NO) through α2-presynaptic receptors. The sympathetic cotransmitter neuropeptide Y (NPY) modulates noradrenergic vasoconstriction in penile small arteries by both enhancing and depressing noradrenaline contractions through Y1- and Y2-postsynaptic and a NO-independent atypical endothelial receptor, respectively. Activation of α1-adrenoceptors involves both Ca2+ influx through L-type and receptor-operated Ca2+ channels (ROC) and Ca2+ sensitization mechanisms mediated by protein kinase C (PKC), tyrosine kinases (TKs) and Rho kinase (RhoK). In addition, RhoK can regulate Ca2+ entry in penile arteries upon receptor stimulation. Vasodilatation of penile arteries and large veins during erection is mediated by neurally released NO. The subsequent increased arterial inflow to the cavernosal sinoids and shear stress on the endothelium lining penile arteries activates endothelial NO production through Akt phosphorylation of endothelial NO synthase (eNOS). NO stimulates guanylate cyclase and increased cyclic guanin 3′-monophosphate (cGMP) levels in turn activate protein kinase G (PKG), which enhances K+ efflux through Ca2+-activated (KCa) and voltage-dependent Ca2+ (Kv) channels in penile arteries and veins, respectively. PKG-mediated decrease in Ca2+ sensitivity and its regulation by RhoK remains to be clarified in penile vasculature. Phosphodiesterase type 5 (PDE5) inhibitors are potent vasodilators of penile resistance arteries and increase the content and effects of basally released endothelial NO. Endothelium-dependent relaxations of penile small arteries also include an endothelium-derived hyperpolarizing factor (EDHF)-type response, which is impaired in diabetes and hypertension-associated ED. Locally produced contractile and relaxant prostanoids regulate penile venous and arterial tone, respectively. The latter activates prostaglandin I (IP) and prostaglandin E (EP) receptors coupled to adenylate cyclase and to the increase of cyclic adenosine monophosphate (cAMP) levels, which in turn stimulates K+ efflux through ATP-sensitive K+ (KATP) channels. There is a crosstalk between the cGMP and cAMP signaling pathways in penile small arteries. Relevant issues such as the mechanisms underlying the excitation–secretion coupling of the endothelial cells, as well as those involved in cell proliferation and vascular remodeling of the penile vasculature remain to be elucidated. In addition, only few studies have investigated the changes in structure and function of penile arteries in cardiovascular risk situations leading to ED.

This is a preview of subscription content, access via your institution

Access options

Buy this article

  • Purchase on SpringerLink
  • Instant access to full article PDF
Buy now

Prices may be subject to local taxes which are calculated during checkout

Figure 1
Figure 2

Similar content being viewed by others

References

  1. Lue TF . Erectile dysfunction. New Engl J Med 2000; 342: 1802–1813.

    CAS  PubMed  Google Scholar 

  2. Sullivan ME, Thompson CS, Dashwood MR, Khan MA, Jeremy JY, Morgan RJ et al. Nitric oxide and penile erection: is erectile dysfunction another manifestation of vascular disease? Cardiovasc Res 1999; 43: 658–665.

    CAS  PubMed  Google Scholar 

  3. Montorsi P, Montorsi F, Schukman C . Is erectile dysfunction the tip of the iceberg of a systemic vascular disorder? Eur Urol 2003; 44: 352–354.

    PubMed  Google Scholar 

  4. Andersson KE, Wagner G . Physiology of penile erection. Physiol Rev 1995; 75: 191–236.

    CAS  PubMed  Google Scholar 

  5. Broderick GA . Evidence based assessment of erectile dysfunction. Int J Impot Res 1998; 10: S64–S73.

    PubMed  Google Scholar 

  6. Simonsen U, García-Sacristán A, Prieto D . Penile arteries and erection. J Vasc Res 2002; 39: 283–303.

    CAS  PubMed  Google Scholar 

  7. Montorsi F, Sarteschi M, Maga T, Guazzoni G, Fabris GF, Rigatti P et al. Functional anatomy of cavernous helicine arterioles in potent subjects. J Urol 1998; 159: 808–810.

    CAS  PubMed  Google Scholar 

  8. Saenz de Tejada I, Angulo J, Cellek S, Gonzalez-Cadavid N, Heaton J, Pickard R et al. Physiology of erectile function and pathophysiology of erectile dysfunction. In: Lue TF, Bason R, Rosen R, Guliano F, Khoury S, Montorsi F (eds). Sexual Medicine: Sexual Dysfunctions in Men and Woman. Health Publications: Paris, 2004, pp 287–344.

    Google Scholar 

  9. Saenz de Tejada I, Moroukian P, Tessier J, Kim J, Goldstein I, Frohrib D . Trabecular smooth muscle modulates the capacitor function of the penis. Studies on a rabbit model. Am J Physiol 1991; 260: H1590–H1595.

    CAS  PubMed  Google Scholar 

  10. Udelson D, L'Esperance J, Morales AM, Patel R, Goldstein I . The mechanics od corporal veno-occlusion in penile erection: a theory on the effect of stretch-associated luminal constrictability on outflow resistance. Int J Impot Res 2000; 12: 315–327.

    CAS  PubMed  Google Scholar 

  11. Kirkeby HJ, Forman A, Sorensen S, Andersson KE . Alpha-adrenoceptor function in isolated penile circumflex veins from potent and impotent men. J Urol 1989; 142: 1369–1371.

    CAS  PubMed  Google Scholar 

  12. Kirkeby HJ, Jorgensen JC, Ottesen B . Neuropeptide Y (NPY) in human penile corpus cavernosum tissue and circumflex veins—occurrence and in vitro effects. J Urol 1991; 145: 605–609.

    CAS  PubMed  Google Scholar 

  13. Hayashida H, Fujimoto H, Yoshida K, Tomoyoshi T, Okamura T, Toda N . Comparison of neurogenic contraction and relaxation in canine corpus cavernosum and penile artery and vein. Jpn J Pharmacol 1996; 72: 231–240.

    CAS  PubMed  Google Scholar 

  14. Segarra G, Medina P, Domenech C, Martinez Leon JB, Vila JM, Aldasoro M et al. Neurogenic contraction and relaxation of human penile deep dorsal vein. Br J Pharmacol 1998; 124: 788–794.

    CAS  PubMed  PubMed Central  Google Scholar 

  15. Segarra G, Medina P, Domenech C, Vila JM, Martinez-Leon JB, Aldasoro M et al. Role of vasopressin on adrenergic neurotransmission in human penile blood vessels. J Pharmacol Exp Ther 1998; 286: 1315–1320.

    CAS  PubMed  Google Scholar 

  16. Martinez AC, Prieto D, Hernandez M, Rivera L, Recio P, Garcia-Sacristan A et al. Endothelial mechanisms underlying responses to ACh in the horse deep dorsal penile vein. Eur J Pharmacol 2005; 515: 150–159.

    CAS  PubMed  Google Scholar 

  17. Martinez AC, Hernandez M, Rivera L, Recio P, Garcia-Sacristan A, Benedito S . Muscarinic receptor subtypes mediate vasorelaxation in isolated horse deep dorsal penile vein. Urology 2003; 62: 357–361.

    PubMed  Google Scholar 

  18. Melman A, Gingell JC . The epidemiology and pathophysiology of erectile dysfunction. J Urol 1999; 161: 5–11.

    CAS  PubMed  Google Scholar 

  19. Martinez AC, Stankevicius E, Jakobsen P, Simonsen U . Blunted non-nitric oxide vasodilatory neurotransmission in penile arteries from renal hypertensive rats. Vascul Pharmacol 2006; 44: 354–362.

    CAS  PubMed  Google Scholar 

  20. Giuliano F, Bernabe J, Jardin A, Rousseau JP . Antierectile role of the sympathetic nervous system in rats. J Urol 1993; 150: 519–524.

    CAS  PubMed  Google Scholar 

  21. Saenz de Tejada I, Kim N, Lagan I, Krane RJ, Goldstein I . Regulation of adrenergic activity in penile corpus cavernosum. J Urol 1989b; 142: 1117–1121.

    CAS  PubMed  Google Scholar 

  22. Hedlund H, Andersson K-E . Comparison of the responses to drugs acting on adrenoreceptors and muscarinic receptors in human isolated corpus cavernosum and cavernous artery. J Auton Pharmacol 1985; 5: 81–88.

    CAS  PubMed  Google Scholar 

  23. Simonsen U, Prieto D, Hernández M, García Sacristán A . Adrenoceptor-mediated regulation of the contractility in horse penile resistance arteries. J Vasc Res 1997; 34: 90–102.

    CAS  PubMed  Google Scholar 

  24. Recio P, Prieto D, Martinez MP, Garcia P, Rivera L, Benedito S et al. Immunohistochemical and functional evidence for a noradrenergic regulation in the horse penile deep dorsal vein. Int J Impot Res 2004; 16: 486–491.

    CAS  PubMed  Google Scholar 

  25. Wespes E, Schiffmann S, Gilloteaux J, Schulman C, Vierendeels G, Menu R et al. Study of neuropeptide Y-containing nerve fibers in the human penis. Cell Tissue Res 1988; 254: 69–74.

    CAS  PubMed  Google Scholar 

  26. Prieto D, Rivera L, Martínez P, Benedito S, García-Sacristán A, Hernández M . Heterogeneity of the neuropeptide Y (NPY) contractile and relaxing receptors in horse penile small arteries. Br J Pharmacol 2004; 143: 976–986.

    CAS  PubMed  PubMed Central  Google Scholar 

  27. Kirkeby HJ, Lundbech PE, Djurhuus JC, Forman A . Effects of vasoactive intestinal peptide, peptide histidine methionine, and neuropeptide Y on intracavernous pressure in the rabbit. Urology 1992; 40: 270–276.

    CAS  PubMed  Google Scholar 

  28. Prieto D, Buus C, Mulvany MJ, Nilsson H . Interactions between neuropeptide Y and the adenylate cyclase pathway in rat mesenteric small arteries: role of membrane potential. J Physiol 1997; 502: 281–292.

    CAS  PubMed  PubMed Central  Google Scholar 

  29. Prieto D, Buus CL, Mulvany MJ, Nilsson H . Neuropeptide Y regulates intracellular calcium through different signalling pathways linked to a Y(1)-receptor in rat mesenteric small arteries. Br J Pharmacol 2000; 129: 1689–1699.

    CAS  PubMed  PubMed Central  Google Scholar 

  30. Daley JT, Brown ML, Watkins T, Traish AM, Huang YH, Moreland RB et al. Prostanoid production in rabbit corpus cavernosum: I. Regulation by oxygen tension. J Urol 1996; 155: 1482–1487.

    CAS  PubMed  Google Scholar 

  31. Azadzoi KM, Kim N, Brown ML, Goldstein I, Cohen RA, Saenz de Tejada I . Endothelium-derived nitric oxide and cyclooxygenase products modulate corpus cavernosum smooth muscle tone. J Urol 1992; 147: 220–225.

    CAS  PubMed  Google Scholar 

  32. Minhas S, Cartledge J, Eardley I . The role of prostaglandins in penile erection. Prostaglandins Leukot Essent Fatty Acids 2000; 62: 137–146.

    CAS  PubMed  Google Scholar 

  33. Hedlund H, Andersson KE, Fovaeus M, Holmquist F, Uski T . Characterization of contraction-mediating prostanoid receptors in human penile erectile tissues. J Urol 1989; 141: 182–186.

    CAS  PubMed  Google Scholar 

  34. Angulo J, Cuevas P, La Fuente JM, Pomerol JM, Ruiz-Castane E, Puigvert A et al. Regulation of human penile smooth muscle tone by prostanoid receptors. Br J Pharmacol 2002; 136: 23–30.

    CAS  PubMed  PubMed Central  Google Scholar 

  35. Kifor I, Williams GH, Vickers MA, Sullivan MP, Jodbert P, Dluhy RG . Tissue angiotensin II as a modulator of erectile function. I. Angiotensin peptide content, secretion and effects in the corpus cavernosum. J Urol 1997; 157: 1920–1925.

    CAS  PubMed  Google Scholar 

  36. Park JK, Kim SZ, Kim SH, Park YK, Cho KW . Renin angiotensin system in rabbit corpus cavernosum: functional characterization of angiotensin II receptors. J Urol 1997; 158: 653–658.

    CAS  PubMed  Google Scholar 

  37. Becker AJ, Uckert S, Stief CG, Truss MC, Machtens S, Scheller F et al. Possible role of bradykinin and angiotensin II in the regulation of penile erection and detumescence. Urology 2001; 57: 193–198.

    CAS  PubMed  Google Scholar 

  38. Comiter CV, Sullivan MP, Yalla SV, Kifor I . Effect of angiotensin II on corpus cavernosum smooth muscle in relation to nitric oxide environment: in vitro studies in canines. Int J Impot Res 1997; 9: 135–140.

    CAS  PubMed  Google Scholar 

  39. Toblli JE, Stella I, Mazza ON, Ferder L, Inserra F . Different effect of losartan and amlodipine on penile structures in male spontaneously hypertensive rats. Am J Nephrol 2004; 24: 614–623.

    CAS  PubMed  Google Scholar 

  40. Holmquist F, Kirkeby HJ, Larsson B, Forman A, Alm P, Andersson KE . Functional effects, binding sites and immunolocalization of endothelin-1 in isolated penile tissues from man and rabbit. J Pharmacol Exp Ther 1992; 261: 795–802.

    CAS  PubMed  Google Scholar 

  41. Parkkisenniemi UM, Palkama A, Virtanen I, Klinge E . The endothelin ET(B) receptor agonist [125I]BQ-3020 binds predominantly to nerves in the bovine retractor penis muscle and penile artery. Pharmacol Toxicol 2000; 87: 234–241.

    CAS  PubMed  Google Scholar 

  42. Ari G, Vardi Y, Hoffman A, Finberg JP . Possible role for endothelins in penile erection. Eur J Pharmacol 1996; 307: 69–74.

    CAS  PubMed  Google Scholar 

  43. Giraldi A, Serels S, Autieri M, Melman A, Christ GJ . Endothelin-1 as a putative modulator of gene expression and cellular physiology in cultured human corporal smooth muscle cells. J Urol 1998; 160: 1856–1862.

    CAS  PubMed  Google Scholar 

  44. Somlyo AP, Somlyo AV . Signal transduction by G-proteins, rho-kinase and protein phosphatase to smooth muscle and non-muscle myosin II. J Physiol 2000; 522: 177–185.

    CAS  PubMed  PubMed Central  Google Scholar 

  45. Berridge MJ . Calcium signalling: dynamics, homeostasis and remodelling. Nat Rev Mol Cell Biol 2003; 4: 517–529.

    CAS  PubMed  Google Scholar 

  46. McFadzean I, Gibson A . The developing relationship between receptor-operated and store-operated calcium channels in smooth muscle. Br J Pharmacol 2002; 135: 1–13.

    CAS  PubMed  PubMed Central  Google Scholar 

  47. Villalba N, Stankevicius E, Garcia Sacristán A, Simonsen U, Prieto D . Contribution of both Ca2+ entry and Ca2+ sensitization to the α1-adrenergic vasoconstriction of rat penile small arteries. Am J Physiol Heart Circ Physiol 2007; 292: H1157–H1169.

    CAS  PubMed  Google Scholar 

  48. Williams BA, Liu C, Deyoung L, Brock GB, Sims SM . Regulation of intracellular Ca2+ release in corpus cavernosum smooth muscle: synergism between nitric oxide and cGMP. Am J Physiol Cell Physiol 2005; 288: C650–C658.

    CAS  PubMed  Google Scholar 

  49. Golovina VA . Cell proliferation is associated with enhanced capacitative Ca2+ entry in human arterial myocytes. Am J Physiol 1999; 277: C343–C349.

    CAS  PubMed  Google Scholar 

  50. Chitaley K, Wingard CJ, Webb RC, Branam H, Stopper VS, Lewis RW et al. Antagonism of Rho-kinase stimulates rat penile erection via a nitric oxide-independent pathway. Nat Med 2001; 7: 119–122.

    CAS  PubMed  Google Scholar 

  51. Chitaley K, Bivalacqua TJ, Champion HC, Usta MF, Hellstrom WJ, Mills TM et al. Adeno-associated viral gene transfer of dominant negative RhoA enhances erectile function in rats. Biochem Biophys Res Commun 2002; 298: 427–432.

    CAS  PubMed  Google Scholar 

  52. Wang H, Eto M, Steers WD, Somlyo AP, Somlyo AV . RhoA-mediated Ca2+ sensitization in erectile function. J Biol Chem 2002; 277: 30614–30621.

    CAS  PubMed  Google Scholar 

  53. Stanckevicius E, Villalba N, Simonsen U, Prieto D . Rho kinase regulates calcium entry through a non l-type non store-operated calcium channel in rat dorsal penile artery. J Vasc Res 2006; 43 (Suppl 1): 54.

    Google Scholar 

  54. Moncada S, Higgs EA . The discovery of nitric oxide and its role in vascular biology. Br J Pharmacol 2006; 147 (Suppl 1): S193–S201.

    CAS  PubMed  PubMed Central  Google Scholar 

  55. Burnett AL, Lowenstein CJ, Bredt DS, Chang TS, Snyder SH . Nitric oxide: a physiologic mediator of penile erection. Science 1992; 257: 401–403.

    CAS  PubMed  Google Scholar 

  56. Hedlund P, Alm P, Andersson KE . NO synthase in cholinergic nerves and NO-induced relaxation in the rat isolated corpus cavernosum. Br J Pharmacol 1999; 127: 349–360.

    CAS  PubMed  PubMed Central  Google Scholar 

  57. Hedlund P, Ny L, Alm P, Andersson KE . Cholinergic nerves in human corpus cavernosum and spongiosum contain nitric oxide synthase and heme oxygenase. J Urol 2000; 164: 868–875.

    CAS  PubMed  Google Scholar 

  58. Dail WG, Barba V, Leyba L, Galindo R . Neural and endothelial nitric oxide synthase activity in rat penile erectile tissue. Cell Tissue Res 1995; 282: 109–116.

    CAS  PubMed  Google Scholar 

  59. Simonsen U, Prieto D, Saenz de Tejada I, Garcia-Sacristan A . Involvement of nitric oxide in the non-adrenergic non-cholinergic neurotransmission of horse deep penile arteries: role of charybdotoxin-sensitive K(+)-channels. Br J Pharmacol 1995; 116: 2582–2590.

    CAS  PubMed  PubMed Central  Google Scholar 

  60. Simonsen U, Prieto D, Delgado JA, Hernandez M, Resel L, Sáenz de Tejada I et al. Nitric oxide is involved in the inhibitory neurotransmission and endothelium-dependent relaxations of human small penile arteries. Clin Sci 1997; 92: 269–275.

    CAS  Google Scholar 

  61. Prieto D, Simonsen U, Hernández M, García-Sacristán A . Contribution of K+ channels and ouabain-sensitive mechanisms to the endothelium-dependent relaxations of horse penile small arteries. Br J Pharmacol 1998; 123: 1609–1620.

    CAS  PubMed  PubMed Central  Google Scholar 

  62. Kirkeby HJ, Svane D, Poulsen J, Tottrup A, Forman A, Andersson KE . Role of the L-arginine/nitric oxide pathway in relaxation of isolated human penile cavernous tissue and circumflex veins. Acta Physiol Scand 1993; 149: 385–392.

    CAS  PubMed  Google Scholar 

  63. Burnett AL, Nelson RJ, Calvin DC, Liu JX, Demas GE, Klein SL et al. Nitric oxide-dependent penile erection in mice lacking neuronal nitric oxide synthase. Mol Med 1996; 2: 288–296.

    CAS  PubMed  PubMed Central  Google Scholar 

  64. Burnett AL, Chang AG, Crone JK, Huang PL, Sezen SE . Noncholinergic penile erection in mice lacking the gene for endothelial nitric oxide synthase. J Androl 2002; 23: 92–97.

    CAS  PubMed  Google Scholar 

  65. Gonzalez-Cadavid NF, Burnett AL, Magee TR, Zeller CB, Vernet D, Smith N et al. Expression of penile neuronal nitric oxide synthase variants in the rat and mouse penile nerves. Biol Reprod 2000; 63: 704–714.

    CAS  PubMed  Google Scholar 

  66. Hurt KJ, Sezen SF, Champion HC, Crone JK, Palese MA, Huang PL et al. Alternatively spliced neuronal nitric oxide synthase mediates penile erection. Proc Natl Acad Sci USA 2006; 103: 3440–3443.

    CAS  PubMed  PubMed Central  Google Scholar 

  67. Simonsen U, Prieto D, Hernández M, Saénz de Tejada I, García-Sacristán A . Prejunctional alpha2-adrenoceptors inhibit the non-adrenergic non-cholinergic neurogenic relaxations in horse penile resistance arteries. J Urol 1997; 157: 2356–2360.

    CAS  PubMed  Google Scholar 

  68. Simonsen U, Contreras J, Garcia-Sacristan A, Martinez AC . Effect of sildenafil on non-adrenergic non-cholinergic neurotransmission in bovine penile small arteries. Eur J Pharmacol 2001; 412: 155–169.

    CAS  PubMed  Google Scholar 

  69. Lugg J, Ng C, Rajfer J, Gonzalez-Cadavid N . Cavernosal nerve stimulation in the rat reverses castration-induced decrease in penile NOS activity. Am J Physiol 1996; 271: E354–E361.

    CAS  PubMed  Google Scholar 

  70. Escrig A, Marin R, Mas M . Repeated PGE1 treatment enhances nitric oxide and erection responses to nerve stimulation in the rat penis by upregulating constitutive NOS isoforms. J Urol 1999; 162: 2205–2210.

    CAS  PubMed  Google Scholar 

  71. Kim N, Vardi Y, Padma-Nathan H, Daley J, Goldstein I, Saenz de Tejada I . Oxygen tension regulates the nitric oxide pathway. Physiological role in penile erection. J Clin Invest 1993; 91: 437–442.

    CAS  PubMed  PubMed Central  Google Scholar 

  72. Azadzoi KM . Vasculogenic erectile dysfunction: beyond the haemodynamic changes. BJU Int 2006; 97: 11–16.

    PubMed  Google Scholar 

  73. Moreland RB, Albadawi H, Bratton C, Patton G, Goldstein I, Traish A et al. O2-dependent prostanoid synthesis activates functional PGE receptors on corpus cavernosum smooth muscle. Am J Physiol Heart Circ Physiol 2001; 281: H552–H558.

    CAS  PubMed  Google Scholar 

  74. Martinez AC, Prieto D, Raposo R, Delgado JA, Resel L, Garcia-Sacristan A et al. Endothelium-independent relaxation induced by histamine in human dorsal penile artery. Clin Exp Pharmacol Physiol 2000; 27: 500–507.

    CAS  PubMed  Google Scholar 

  75. Ruiz Rubio JL, Hernandez M, Rivera de los Arcos L, Martinez AC, Garcia-Sacristan A, Prieto D . Mechanisms of prostaglandin E1-induced relaxation in penile resistance arteries. J Urol 2004; 171: 968–973.

    CAS  PubMed  Google Scholar 

  76. Rivera de los Arcos LR, Prieto D, Martinez AC, Benedito S, Hernandez M, Garcia-Sacristan A . An in vitro method of studying functional responses of penile resistance arteries under isobaric conditions. J Urol 2004; 171: 1974–1978.

    PubMed  Google Scholar 

  77. Angulo J, Cuevas P, Moncada I, Martin-Morales A, Allona A, Fernandez A et al. Rationale for the combination of PGE(1) and S-nitroso-glutathione to induce relaxation of human penile smooth muscle. J Pharmacol Exp Ther 2000; 295: 586–593.

    CAS  PubMed  Google Scholar 

  78. Moreland RB, Hsieh G, Nakane M, Brioni JD . The biochemical and neurologic basis for the treatment of male erectile dysfunction. J Pharmacol Exp Ther 2001; 296: 225–234.

    CAS  PubMed  Google Scholar 

  79. Nehra A, Azadzoi KM, Moreland RB, Pabby A, Siroky MB, Krane RJ et al. Cavernosal expandability is an erectile tissue mechanical property which predicts trabecular histology in an animal model of vasculogenic erectile dysfunction. J Urol 1998; 159: 2229–2236.

    CAS  PubMed  Google Scholar 

  80. Seftel AD, Sun P, Swindle R . The prevalence of hypertension, hyperlipidemia, diabetes mellitus and depression in men with erectile dysfunction. J Urol 2004; 171: 2341–2345.

    PubMed  Google Scholar 

  81. Busse R, Fleming I . Regulation of endothelium-derived vasoactive autacoid production by hemodynamic forces. Trends Pharmacol Sci 2003; 24: 24–29.

    CAS  PubMed  Google Scholar 

  82. Liu XR, Gillespie JS, Gibson IF, Martin W . Effects of NG-substituted analogues of L-arginine on NANC relaxation of the rat anococcygeus and bovine retractor penis muscles and the bovine penile artery. Br J Pharmacol 1991; 104: 53–58.

    CAS  PubMed  PubMed Central  Google Scholar 

  83. Angulo J, Cuevas P, Fernandez A, Gabancho S, Videla S, Saenz de Tejada I . Calcium dobesilate potentiates endothelium-derived hyperpolarizing factor-mediated relaxation of human penile resistance arteries. Br J Pharmacol 2003; 139: 854–862.

    CAS  PubMed  PubMed Central  Google Scholar 

  84. Angulo J, Cuevas P, Fernandez A, Gabancho S, Allona A, Martin-Morales A et al. Diabetes impairs endothelium-dependent relaxation of human penile vascular tissues mediated by NO and EDHF. Biochem Biophys Res Commun 2003; 312: 1202–1208.

    CAS  PubMed  Google Scholar 

  85. Virag R, Floresco J, Richard G . Impairment of shear-stress-mediated vasodilation of cavernous arteries in erectile dysfunction. Int J Impot Res 2004; 16: 39–42.

    CAS  PubMed  Google Scholar 

  86. Joannides R, Haefeli WE, Linder L, Richard V, Bakkali EH, Thuillez C et al. Nitric oxide is responsible for flow-dependent dilatation of human peripheral conduit arteries in vivo. Circulation 1995; 91: 1314–1319.

    CAS  PubMed  Google Scholar 

  87. Paniagua OA, Bryant MB, Panza JA . Role of endothelial nitric oxide in shear stress-induced vasodilation of human microvasculature: diminished activity in hypertensive and hypercholesterolemic patients. Circulation 2001; 103: 1752–1758.

    CAS  PubMed  Google Scholar 

  88. Hurt KJ, Musicki B, Palese MA, Crone JK, Becker RE, Moriarity JL et al. Akt-dependent phosphorylation of endothelial nitric-oxide synthase mediates penile erection. Proc Natl Acad Sci USA 2002; 99: 4061–4066.

    CAS  PubMed  PubMed Central  Google Scholar 

  89. Dimmeler S, Fleming I, Fisslthaler B, Hermann C, Busse R, Zeiher AM . Activation of nitric oxide synthase in endothelial cells by Akt-dependent phosphorylation. Nature 1999; 399: 601–605.

    CAS  PubMed  Google Scholar 

  90. Bivalacqua TJ, Usta MF, Champion HC, Kadowitz PJ, Hellstrom WJ . Endothelial dysfunction in erectile dysfunction: role of the endothelium in erectile physiology and disease. J Androl 2003; 24 (Suppl 6): S17–S37.

    CAS  PubMed  Google Scholar 

  91. Ming XF, Viswambharan H, Barandier C, Ruffieux J, Kaibuchi K, Rusconi S et al. Rho GTPase/Rho kinase negatively regulates endothelial nitric oxide synthase phosphorylation through the inhibition of protein kinase B/Akt in human endothelial cells. Mol Cell Biol 2002; 22: 8467–8477.

    CAS  PubMed  PubMed Central  Google Scholar 

  92. Bivalacqua TJ, Champion HC, Usta MF, Cellek S, Chitaley K, Webb RC et al. RhoA/Rho-kinase suppresses endothelial nitric oxide synthase in the penis: a mechanism for diabetes-associated erectile dysfunction. Proc Natl Acad Sci USA 2004; 101: 9121–9126.

    CAS  PubMed  PubMed Central  Google Scholar 

  93. Busse R, Edwards G, Feletou M, Fleming I, Vanhoutte PM, Weston AH . EDHF: bringing the concepts together. Trends Pharmacol Sci 2002; 23: 374–380.

    CAS  PubMed  Google Scholar 

  94. Kun A, Martinez AC, Tanko LB, Pataricza J, Papp JG, Simonsen U . Ca2+-activated K+ channels in the endothelial cell layer involved in modulation of neurogenic contractions in rat penile arteries. Eur J Pharmacol 2003; 474: 103–115.

    CAS  PubMed  Google Scholar 

  95. Saenz de Tejada I, Goldstein I, Azadzoi K, Krane RJ, Cohen RA . Impaired neurogenic and endothelium-mediated relaxation of penile smooth muscle from diabetic men with impotence. New Engl J Med 1989; 320: 1025–1030.

    CAS  PubMed  Google Scholar 

  96. Behr-Roussel D, Gorny D, Mevel K, Compagnie S, Kern P, Sivan V et al. Erectile dysfunction in spontaneously hypertensive rats: pathophysiological mechanisms. Am J Physiol Regul Integr Comp Physiol 2003; 284: R682–R688.

    CAS  PubMed  Google Scholar 

  97. Gupta S, Moreland RB, Munarriz R, Daley J, Goldstein I, Saenz de Tejada I . Possible role of Na(+)-K(+)-ATPase in the regulation of human corpus cavernosum smooth muscle contractility by nitric oxide. Br J Pharmacol 1995; 116: 2201–2206.

    CAS  PubMed  PubMed Central  Google Scholar 

  98. Hedlund P, Aszodi A, Pfeifer A, Alm P, Hofmann F, Ahmad M et al. Erectile dysfunction in cyclic GMP-dependent kinase I-deficient mice. Proc Natl Acad Sci USA 2000; 97: 2349–2354.

    CAS  PubMed  PubMed Central  Google Scholar 

  99. Schlossmann J, Fiel R, Hofmann F . Signalling through NO and cGMP-dependent protein kinases. Ann Med 2003; 35: 21–27.

    CAS  PubMed  Google Scholar 

  100. Christ GJ . K channels as molecular targets for the treatment of erectile dysfunction. J Androl 2002; 23: S10–S19.

    CAS  PubMed  Google Scholar 

  101. Prieto D, Rivera L, Benedito S, Recio P, Villalba N, Hernandez M et al. Ca2+-activated K+ (KCa) channels are involved in the relaxations elicited by sildenafil in penile resistance arteries. Eur J Pharmacol 2006; 531: 232–237.

    CAS  PubMed  Google Scholar 

  102. Sauzeau V, Le Jeune H, Cario-Toumaniantz C, Smolenski A, Lohmann SM, Bertoglio J et al. Cyclic GMP-dependent protein kinase signaling pathway inhibits RhoA-induced Ca2+ sensitization of contraction in vascular smooth muscle. J Biol Chem 2000; 275: 21722–21729.

    CAS  PubMed  Google Scholar 

  103. Mills TM, Chitaley K, Lewis RW, Webb RC . Nitric oxide inhibits RhoA/Rho-kinase signaling to cause penile erection. Eur J Pharmacol 2002; 439: 173–174.

    CAS  PubMed  Google Scholar 

  104. Linder AE, Leite R, Lauria K, Mills TM, Webb RC . Penile erection requires association of soluble guanylyl cyclase with endothelial caveolin-1 in rat corpus cavernosum. Am J Physiol Regul Integr Comp Physiol 2006; 290: R1302–R1308.

    CAS  PubMed  Google Scholar 

  105. Seftel AD . Phosphodiesterase type 5 inhibitors: molecular pharmacology and interactions with other phosphodiesterases. Curr Pharm Des 2005; 11: 4047–4058.

    CAS  PubMed  Google Scholar 

  106. Lin CS, Lau A, Tu R, Lue TF . Expression of three isoforms of cGMP-binding cGMP-specific phosphodiesterase (PDE5) in human penile cavernosum. Biochem Biophys Res Commun 2000; 268: 628–635.

    CAS  PubMed  Google Scholar 

  107. Lin CS, Chow S, Lau A, Tu R, Lue TF . Identification and regulation of human PDE5A gene promoter. Biochem Biophys Res Commun 2001; 280: 684–692.

    CAS  PubMed  Google Scholar 

  108. Waldkirch E, Uckert S, Yildirim H, Sohn M, Jonas U, Stief CG et al. Cyclic AMP-specific and cyclic GMP-specific phosphodiesterase isoenzymes in human cavernous arteries—immunohistochemical distribution and functional significance. World J Urol 2005; 23: 405–410.

    CAS  PubMed  Google Scholar 

  109. Prieto D, Rivera L, Recio P, Rubio JL, Hernandez M, Garcia-Sacristan A . Role of nitric oxide in the relaxation elicited by sildenafil in penile resistance arteries. J Urol 2006; 175: 1164–1170.

    CAS  PubMed  Google Scholar 

  110. Ballard SA, Gingell CJ, Tang K, Turner LA, Price ME, Naylor AM . Effects of sildenafil on the relaxation of human corpus cavernosum tissue in vitro and on the activities of cyclic nucleotide phosphodiesterase isozymes. J Urol 1998; 159: 2164–2171.

    CAS  PubMed  Google Scholar 

  111. Ruiz Rubio JL, Hernandez M, Rivera de los Arcos L, Benedito S, Recio P, Garcia P et al. Role of ATP-sensitive K+ channels in relaxation of penile resistance arteries. Urology 2004; 63: 800–805.

    PubMed  Google Scholar 

  112. Lee SW, Wang HZ, Zhao W, Ney P, Brink PR, Christ GJ . Prostaglandin E1 activates the large-conductance KCa channel in human corporal smooth muscle cells. Int J Impot Res 1999; 11: 189–199.

    CAS  PubMed  Google Scholar 

  113. Stief CG, Uckert S, Becker AJ, Harringer W, Truss MC, Forssmann WG et al. Effects of sildenafil on cAMP and cGMP levels in isolated human cavernous and cardiac tissue. Urology 2000; 55: 146–150.

    CAS  PubMed  Google Scholar 

Download references

Acknowledgements

Dolores Prieto was supported by Grants no. PR1/06-14441-A from the Universidad Complutense de Madrid and Grant no. SAF2006-09191 from the Ministerio de Educación y Ciencia (España).

Author information

Authors and Affiliations

  1. Departamento de Fisiología, Facultad de Farmacia, Universidad Complutense de Madrid, Madrid, Spain

    D Prieto

Authors
  1. D Prieto
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to D Prieto.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Prieto, D. Physiological regulation of penile arteries and veins. Int J Impot Res 20, 17–29 (2008). https://doi.org/10.1038/sj.ijir.3901581

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/sj.ijir.3901581

Keywords

This article is cited by

Search

Advanced search

Quick links