Skip to main content
SpringerLink
Log in

Regulation of tone in penile cavernous smooth muscle

Established concepts and new findings

  • Published:
World Journal of Urology Aims and scope Submit manuscript

Summary

Since Benson, in 1983, reported on a potent nonadrenergic, noncholinergic (NANC) transmitter postulated to relax penile vessels and the corpus cavernosum, much new information on the mechanisms of contraction and relaxation of corporeal smooth muscle and penile vasculature has been obtained. The information currently available suggests that NANC transmitters may be involved in both contractile and relaxant responses of penile erectile tissues. There is good experimental evidence to allow the assumption that neurogenic nitric oxide (NO) is a mediator of penile erection, but even if NO probably is the most important factor for relaxation of penile vessels and the corpus cavernosum, this does not exclude the possibility that other agents released from nerves may have a modulatory function in this process. However, the roles of, for example, vasoactive intestinal polypeptide and related peptides as neurotransmitters and/or neuromodulators in the nervous control of penile erection have yet to be established. The restricted availability of human penile erectile tissues has led to the use of cavernous tissue and penile vessels from animals, both for screening and for detailed analysis of mechanisms previously demonstrated to exist also in human tissues. When interpreting the results obtained, it is important to stress that there may be important differences between human and animal tissues, that each of the tissues only gives a piece of information on the complex process of penile erection, and that the physiological and clinical importance of results from such experiments may be limited. The differing responses in different parts of the vasculature within the penis and the multiplicity of putative transmitters present in the corpus cavernosum and in perivascular nerves make further investigations necessary, as do the interactions between transmitters and neuromodulators at the neuromuscular junction, and between the neural and endothelial control of vascular tone.

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

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

References

  1. Aboseif SR, Riemer RK, Stackl W, Lue TF, Tanagho EA (1993) Quantification of prostaglandin receptors in cavernous tissue of men, monkeys and dogs. Urol Int 50:148–152

    Google Scholar 

  2. Adaikan PG (1979) Pharmacology of the human penis. MSc Thesis, University of Singapore

  3. Adaikan PG, Karim SM (1977) Effects of histamine on the human penis muscle in vitro. Eur J Pharmacol 45:261–265

    Google Scholar 

  4. Adaikan PG, Kottegoda SR, Ratnam SS (1986) Is vasoactive intestinal polypeptide the principal transmitter involved in human penile erection? J Urol 135:638–640

    Google Scholar 

  5. Adaikan PG, Lau LC, Ng SC, Ratnam SS (1991) Physiopharmacology of human penile erection — autonomic/nitrergic neurotransmission and receptors of the human corpus cavernosum. Asia Pac J Pharmacol 6:213–227

    Google Scholar 

  6. Adrian TE, Gu J, Allen JM, Tatemoto K, Polak JM, Bloom SR (1984) Neuropeptide Y in the human male genital tract. Life Sci 35:2643–2648

    Google Scholar 

  7. Andersson K-E (1993) The pharmacology of lower urinary tract smooth muscles and penile erectile tissues. Pharmacol Rev 45:253–308

    Google Scholar 

  8. Andersson K-E, Holmquist F (1990) Mechansims for contraction and relaxation of human penile smooth muscle. Int J Impotence Res 2:209–225

    Google Scholar 

  9. Andersson K-E, Hedlund H, Mattiasson A, Sjögren C, Sundler F (1983) Relaxation of isolated human corpus spongiosum induced by vasoactive intestinal polypeptide, substance P, carbachol and electrical field stimulation. World J Urol 1:203–208

    Google Scholar 

  10. Andersson K-E, Fovaeus M, Hedlund H, Lundin S (1986) Characterization of immunoreactive arginine vasopressin (AVP) in and effects of AVP on isolated human penile erectile tissue. J Urol 137:1278–1282

    Google Scholar 

  11. Andersson P-O, Bloom SR, Melander S (1984) Hemodynamics of pelvic nerve induced penile erection in the dog: possible mediation by vasoactive intestinal polypeptide. J Physiol (Lond) 350:209–224

    Google Scholar 

  12. Aoki H, Takagane H, Matzuzaka J, Banya Y, Fujioka T, Nakaya S, Kubo T, Ohhori T (1989) Quantitative analysis of outflow pathway of corpora cavernosa by pressure flow technique. J Urol 141:645–650

    Google Scholar 

  13. Azadzoi KM, Saenz de Tejada I (1991) Hypercholesterolemia impairs endothelium-dependent relaxation of rabbit corpus cavernosum smooth muscle. J Urol 146:238–240

    Google Scholar 

  14. Azadzoi KM, Saenz de Tejada I (1992) Diabetes mellitus impairs neurogenic and endothelium-dependent relaxation of rabbit corpus cavernosum smooth muscle. J Urol 148:1587–1591

    Google Scholar 

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

    Google Scholar 

  16. Bacq ZM (1935) Recherches sur la physiologie et al pharmacologie du système nerveux autonome. XII. Nature cholinergique et adrénergique des diverses innervations vasomotrices du pénis chez la chien. Arch Int Physiol 40:311–321

    Google Scholar 

  17. Berridge MJ (1987) Inositol trisphosphate and diacylglycerol: two interacting second messengers. Annu Rev Biochem 56:159–193

    Google Scholar 

  18. Bornman M, Franz RC, Jacobs DJ, Du Plessis DJ (1986) Thromboxane B2 production during erection. Andrologia 18:220–223

    Google Scholar 

  19. Bosch RJLH, Benard F, Aboseif SR, Stief CG, Stackl W, Lue TF, Tanagho EA (1989) Changes in penile hemodynamics after intracavernous injection of prostaglandin E1 and prostaglandin I2 in pigtailed monkeys. Int J Impotence Res 1:211–221

    Google Scholar 

  20. Bowman A, Drummond AH (1984) Cyclic GMP mediates neurogenic relaxation in the bovine retractor penis muscle. Br J Pharmacol 81:665–674

    Google Scholar 

  21. Bowman A, Gillespie JS (1983) Neurogenic vasodilatation in isolated bovine and canine penil arteries. J Physiol (Lond) 341:603–616

    Google Scholar 

  22. Brinton RE, Gruener R (1987) Vasopressin promotes neurite growth in cultured embryonic neurons. Synapse 1:329–334

    Google Scholar 

  23. Brock G, Breza J, Lue TF (1993) Intracavernous sodium nitroprusside: inappropriate impotence treatment. J Urol 150:864–867

    Google Scholar 

  24. Broderick G, Hypolite J, Levin RM (1991) In-vitro contractile response of the rabbit corpus cavernosa to field stimulation and autonomic agonists and antagonists: a qualitative study. Neurourol Urodyn 10:507–515

    Google Scholar 

  25. Broderick G, Gordon D, Hypolite J, Levin RM (1994) Anoxia and corporeal smooth muscle dysfunction: a model for ischemic priapism. J Urol 151:259–262

    Google Scholar 

  26. Burnett AL, Lowenstein CJ, Bredt DS, Chang TSK, Snyder SH (1992) Nitric oxide: a physiologic mediator of penile erection. Science 257:401–403

    CAS  PubMed  Google Scholar 

  27. Burnett AL, Tillman SL, Chang TSK, Epstein JI, Lowenstein CJ, Bredt DS, Snyder SH, Walsh PC (1993) Immunohistochemical localization of nitric oxide synthase in the autonomic innervation of the human penis. J Urol 150:73–76

    Google Scholar 

  28. Bush PA, Aronson WJ, Buga GM, Rajfer J, Ignarro LJ (1992) Nitric oxide is a potent relaxant of human and rabbit corpus cavernosum. J Urol 147:1650–1655

    Google Scholar 

  29. Bush PA, Aronson WJ, Rajfer J, Buga GM, Ignarro LJ (1992) Comparison of nonadrenergic, noncholinergic- and nitric oxide-mediated relaxation of corpus cavernosum. Int J Impotence Res 4:85–93

    Google Scholar 

  30. Bush PA, Gonzalez NE, Ignarro LJ (1992) Biosynthesis of nitric oxide and citrulline from L-arginine by constitutive nitric oxide synthase present in rabbit corpus cavernosum. Biochem Biophys Res Commun 186:308–314

    Google Scholar 

  31. Cabanié M, Godfraind T (1988) The role of histamine in the cardiovascular system. Drugs Exp Clin Res 14:141–147

    Google Scholar 

  32. Campos de Carvalho AC, Roy C, Moreno AP, Melman A, Hertzberg EL, Christ GJ, Spray DC (1993) Gap junctions formed of connexin43 found between smooth muscle cells of human corpus cavernosum. J Urol 149:1568–1575

    Google Scholar 

  33. Carati CJ, Creed KE, Keogh EJ (1987) Autonomic control of penile erection in dogs. J Physiol (Lond) 384:525–538

    Google Scholar 

  34. Carati CJ, Creed KE, Keogh EJ (1988) Vascular changes during erection in the dog. J Physiol (Lond) 400:75–88

    Google Scholar 

  35. Christ GJ, Maayani S, Valcic M, Melman A (1990) Pharmacological studies of human erectile tissue: characteristics of spontaneous contractions and alterations in α-adrenoceptor responsiveness with age and disease in isolated tissues. Br J Pharmacol 101:375–381

    Google Scholar 

  36. Christ GJ, Moreno AP, Parker ME, Gondre CM, Valcic M, Melman A, Spray DC (1991) Intercellular communication through gap junctions: a potential role in pharmacomechanical coupling and syncytial tissue contraction in vascular smooth muscle isolated from the human corpus cavernosum. Life Sci 49:PL195-PL200

    Google Scholar 

  37. Christ GJ, Moreno AP, Melman A, Spray DC (1992) Gap junction-mediated intercellular diffusion of Ca2+ in cultured human corporal smooth muscle. Am J Physiol 263:C373-C383

    Google Scholar 

  38. Christ GJ, Spray DC, Melman A, Brink P (1992) Electrophysiological studies of ion channels in cultured human corporal smooth muscle cells in culture. In J Impotence Res [Suppl 2] 4:A40

  39. 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 Impotence Res 5:77–96

    Google Scholar 

  40. Chuang D-M (1989) Neurotransmitter receptors and phosphoinositide turnover. Annu Rev Pharmacol Toxicol 29:71–110

    Google Scholar 

  41. Claes H, Baert L (1989) Transcutaneous nitroglycerin therapy in the treatment of impotence. Urol Int 44:309–312

    Google Scholar 

  42. Cocchia D, Rende M, Toesca A, Viola R, Stolfi VM (1990) Immunohistochemical study of neuropeptide Y-containing nerve fibers in the human clitoris and penis. Cell Biol Int Rep 10:865–875

    Google Scholar 

  43. Conti GL (1952) L'érection du pénis humaine et ses bases morphologico-vasculaires. Acta Anat 14:217–262

    Google Scholar 

  44. Costa P, Soulie-Vassal ML, Sarrazin B, Rebillard X, Navratil H, Bali JP (1993) Adrenergic receptors on smooth muscle cells isolated from human penile corpus cavernosum. J Urol 150:859–863

    Google Scholar 

  45. Crossman D, McEwan J, MacDermot I, MacIntyre I, Dollery CT (1987) Human calcitonin gene-related peptide activates adenylate cyclase and releases prostacyclin from human umbilical vein endothelial cells. Br J Pharmacol 92:695–701

    Google Scholar 

  46. Crowe R, Lincoln J, Blackley PF, Pryor JP, Lumley JSP, Burnstock G (1983) Vasoactive intestinal polypeptide-like immunoreactive nerves in the diabetic penis: a comparison between streptozotocin-treated rats and man. Diabetes 32:1075–1077

    Google Scholar 

  47. Crowe R, Burnstock G, Dickinson IK, Pryor JP (1991) The human penis: an unusual penetration of NPY-immunoreactive nerves within the medial muscle coat of the deep dorsal vein. J Urol 145:1292–1296

    Google Scholar 

  48. Dahiya R, Trigo-Rocha F, Borck G, Narayan P, Lue T (1993) Sodium nitroprusside and neurostimulation cause increased levels of cylcic guanosine monophosphate and not cyclic adenosine monophosphate during canine penile erection. Biochem Mol Biol Int 29:167–173

    Google Scholar 

  49. Dail WG, Moll MA, Weber K (1983) Localization of vasoactive intestinal polypeptide in penile erectile tissue and in the major pelvic ganglion of the rat. Neuroscience 10:1379–1386

    Google Scholar 

  50. Dail WG, McGuffee L, Minorsky N, Little S (1987) Responses of smooth muscle strips from penile erectile tissue to drugs and transmural nerve stimulation. J Auton Pharmacol 7:287–293

    Google Scholar 

  51. De Groat WC, Booth AM (1993) Neural control of penile erection. In: Maggi CA (ed) The autonomic nervous system, vol 6, ch 13. Nervous control of the urogenital system. Harwood, London, pp 465–513

    Google Scholar 

  52. Delcour C, Wespes E, Vandenbosch G, Schulman CC, Struyven J (1987) The effect of papaverine on arterial and venous hemodynamics of erection. J Urol 138: 187–189

    Google Scholar 

  53. De Mirandacara A, Claro JA, Nahoum C, De Nucci G (1992) Comparison of the penile erection induced by intracavernous injection of papaverine and histamine in patients with psychogenic erection. Int J Impotence Res 4 [Suppl 2]:P137

    Google Scholar 

  54. Derouet H, Eckert R, Trautwein W, Ziegler M (1994) Muscular cavernous single cell analysis in patients with venoocclusive dysfunction. Eur Urol 25:145–150

    Google Scholar 

  55. Djamilian M, Stief CG, Kuczyk M, Jonas U (1993) Followup results of a combination of calcitonin gene-related peptide and prostaglandin E1 in the treatment of erectile dysfunction. J Urol 149:1296–1298

    Google Scholar 

  56. Dorr LD, Brody MJ (1967) Hemodynamic mechanisms of erection in the canine penis. Am J Physiol 213:1526–1531

    Google Scholar 

  57. Emori T, Hirata Y, Ohta K, Shichiri M, Marumo F (1989) Secretory mechanism of immunoreactive endothelin in cultured bovine endothelial cells. Biochem Biophys Res Commun 160:93–100

    Google Scholar 

  58. Feelisch M (1991) The biochemical pathways of nitric oxide formation from nitrovasodilators: appropriate choice of exogenous NO donors and aspects of preparation and handling of aqueous NO solutions. J Cardiovasc Pharmacol 17 [Suppl 3]:S25-S33

    CAS  PubMed  Google Scholar 

  59. Finberg JPM, Vardi Y (1991) Evidence for a role of EDRF in penile erection. Br J Pharmacol 102:82

    Google Scholar 

  60. Finberg JPM, Levy S, Vardi Y (1993) Inhibition of nerve stimulation-induced vasodilatation in corpora cavernosa of the pithed rat by blockade of nitric oxide synthase. Br J Pharmacol 108:1038–1042

    Google Scholar 

  61. Förstermann U, Schmidt HHHW, Pollock JS, Sheng H, Mitchell JA, Warner TD, Nakane M, Murad F (1991) Isoforms of nitric oxide synthase. Biochem Pharmacol 42:1849–1857

    Google Scholar 

  62. Fournier GR, Juenemann K-P, Lue TF, Tanagho EA (1987) Mechanisms of venous occlusion during canine penile erection: an anatomic demonstration. J Urol 137:163–167

    Google Scholar 

  63. Fovaeus M, Andersson K-E, Hedlund H (1987) Effects of some calcium channel blockers on isolated human penile erectile tissue. J Urol 138:1267–1272

    Google Scholar 

  64. Furchgott RF, Zawadzki JV (1980) The obligatory role of endothelial cells in the relaxation of arterial smooth muscle by acetylcholine. Nature 288:373–376

    CAS  PubMed  Google Scholar 

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

    Google Scholar 

  66. Grundemar L, Håkansson R (1993) Multiple neuropeptide Y receptors are involved in cardiovascular regulation. Peripheral and central mechanisms. Gen Pharmacol 24:785–796

    Google Scholar 

  67. Gu J, Polak JM, Probert L, Islam KN, Marangos PJ, Mina S, Adrian TE, McGregor GP, O'Shaughnessy DJ, Bloom SR (1983) Peptidergic innervation of the human male genital tract. J Urol 130:386–391

    Google Scholar 

  68. Gu J, Polak JM, Lazarides M, Morgan R, Pryor JP, Marangos PJ, Blank MA, Bloom SR (1984) Decrease of vasoactive intestinal polypeptide (VIP) in the penises from impotent men. Lancet II:315–318

    Google Scholar 

  69. Haberman JM, Valcic M, Christ G, Melman A (1991) Vasoactive intestinal polypeptide and norepinephrine concentration in the corpora cavernosa of impotent men. Int J Impotence Res 3:21–28

    Google Scholar 

  70. Heaton JPW (1990) Synthetic nitrovasodilators are effective, in vitro, in relaxing penile tissue from impotent men: the findings and their implications. Can J Physiol Pharmacol 67:78–81

    Google Scholar 

  71. Heaton JPW, Morales A, Owen J, Saunders FW, Fenemore J (1989) Topical glyceryltrinitrate causes measurable penile arterial dilatation in impotent men. J Urol 143:729–731

    Google Scholar 

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

    Google Scholar 

  73. Hedlund H, Andersson K-E (1985) Effects of some peptides on isolated human penile erectile tissue and cavernous artery. Acta Physiol Scand 124:413–419

    Google Scholar 

  74. Hedlund H, Andersson K-E (1985) Contraction and relaxation induced by some prostanoids in isolated human penile erectile tissue and cavernous artery. J Urol 134:1245–1250

    Google Scholar 

  75. Hedlund H, Andersson K-E, Fovaeus M, Holmquist F, Uski T (1989) Characterization of contraction-mediating prostanoid receptors in human penile erectile tissues. J Urol 141:182–186

    Google Scholar 

  76. Hedlund H, Andersson K-E, Holmquist F, Uski T (1989) Effect of the thromboxane receptor antagonist AH 23848 on human isolated corpus cavernosum. Int J Impotence Res 1:19–25

    Google Scholar 

  77. Hedlund P, Alm P, Hedlund H, Larsson B, Andersson K-E (1994) Localization and effects of pituitary adenylate cyclase-activating polypeptide (PACAP) in human penile erectile tissues. Acta Physiol Scand 150:103–104

    Google Scholar 

  78. Hedlund P, Alm P, Hedlund H, Larsson B, Andersson K-E (1994) Relaxation of human corpus cavernosum by pituitary adenylate cyclase activating peptide (abstract 1066). J Urol 151:494A

    Google Scholar 

  79. Hedlund P, Holmquist F, Hedlund H, andersson K-E (1994) Effects of nicorandil on human isolated corpus cavernosum and cavernous artery. J Urol 151:1107–1113

    Google Scholar 

  80. Henderson VE, Roepke MH (1933) On the mechanism of erection. Am J Physiol 106:441–448

    Google Scholar 

  81. Holmquist F, Andersson K-E, Hedlund H (1990) Effects of pinacidil on isolated human corpus cavernosum penis. Acta Physiol Scand 138:463–469

    Google Scholar 

  82. Holmquist F, Andersson K-E, Hedlund H (1990) Actions of endothelin on isolated corpus cavernosum from rabbit and man. Acta Physiol Scand 139:113–122

    Google Scholar 

  83. Holmquist F, Hedlund H, Andersson K-E (1991) l-N G-nitro arginine inhibits non-adrenergic, non-cholinergic relaxation of human isolated corpus cavernosum. Acta Physiol Scand 141:441–442

    Google Scholar 

  84. Holmquist F, Stief CG, Jonas U, Andersson K-E (1991) Effects of the nitric oxide synthase inhibitor N G-nitro-l-arginine on the erectile response to cavernous nerve stimulation in the rabbit. Acta Physiol Scand 143:299–304

    Google Scholar 

  85. Holmquist F, Andersson K-E, Hedlund H (1992) Characterization of inhibitory neurotransmission in the isolated corpus cavernosum from rabbit and man. J Physiol (Lond) 449:295–311

    Google Scholar 

  86. Holmquist F, Kirkeby HJ, Larsson B, Forman A, Andersson K-E (1992) Functional effects, binding sites and immunolocalization of endothelin-1 in isolated penile tissues from man and rabbit. J Pharmacol Exp Ther 261:795–802

    Google Scholar 

  87. Holmquist F, Persson K, Garcia-Pascual A, Andersson K-E (1992) Phospholipase C activation by endothelin-1 and noradrenaline in isolated penile erectile tissue from rabbit. J Urol 147:1632–1635

    Google Scholar 

  88. Holmquist F, Fridstrand M, Hedlund H, Andersson K-E (1993) Actions of 3-morpholinosydnonimin (SIN-1) on rabbit isolated penile erectile tissue. J Urol 150:1310–1315

    Google Scholar 

  89. Huang PL, Dawson T, Bredt DS, Snyder SH, Fishman MC (1993) Targeted disruption of the neuronal nitric oxide synthase gene. Cell 75:1273–1286

    Google Scholar 

  90. Huggins JP, Pelton JT, Miller RC (1993) The structure and specificity of endothelin receptors: their importance in physiology and medicine. Pharmacol Ther 59:55–123

    Google Scholar 

  91. Ignarro LJ (1990) Biosynthesis and metabolism of endothelium-derived nitric oxide. Annu Rev Pharmacol Toxicol 30:535–560

    Google Scholar 

  92. Ignarro LJ, Buga GM, Wood KS, Byrns RE, Chaudhury G (1987) Endothelium-derived relaxing factor produced and released from artery and vein is nitric oxide. Proc Natl Acad Sci USA 84:9265–9269

    CAS  PubMed  Google Scholar 

  93. Ignarro LJ, Busch PA, Buga GM, Wood KS, Fukoto JM, Rajfer J (1990) Nitric oxide and cyclic GMP formation upon electrical field stimulation cause relaxation of corpus cavernosum smooth muscle. Biochem Biophys Res Commun 170:843–850

    Google Scholar 

  94. Jeremy JY, Morgan RJ, Mikhailidis DP, Dandona P (1986) Prostacyclin synthesis by the corpora cavernosa of the human penis: evidence for muscarinic control and pathological implications. Prostaglandins Leukotrienes Med 23:211–216

    Google Scholar 

  95. Jünemann K-P (1992) Pharmacotherapy of impotence: where are we going? In: Lue TF (ed) World book of impotence. Smith-Gordon and Company, London, pp 181–188

    Google Scholar 

  96. Juenemann K-P, Alken P (1989) Pharmacotherapy of erectile dysfunction: a review. Int J Impotence Res 1:71–93

    Google Scholar 

  97. Juenemann K-P, Luo J-A, Lue TF, Tanagho EA (1986) Further evidence of venous outflow restriction during erection. Br J Urol 58:320–324

    Google Scholar 

  98. Jünemann K-P, Ehmke H, Kummer W, Mayer B, Bührle CP, Alken P (1993) Coexistence of nitric oxide synthase and vasoactive intestinal polypeptide in nerve terminals of human corpus cavernosum (abstract 127). J Urol 149:245A

    Google Scholar 

  99. Kawanishi Y, Hashine K, Kimura K, Tamura M, Imagawa A (1990) Interaction of VIP and acetylcholine on the relaxation of human corpus cavernosal tissue. Int J Impotence Res 2 [Suppl 2]:9

    Google Scholar 

  100. Keast JR (1992) A possible neural source of nitric oxide in the rat penis. Neurosci Lett 143:69–73

    Google Scholar 

  101. Keast JR, Groat WC de (1989) Immunohistochemical characterization of pelvic neurons which project to the bladder, colon, or penis in rats. J Comp Neurol 288:387–400

    Google Scholar 

  102. Kiely EA, Blank MA, Bloom SR, Williams G (1987) Studies on intracavernosal VIP levels during pharmacologically induced penile erections. Br J Urol 59:334–339

    Google Scholar 

  103. Kiely EA, Bloom SR, Williams G (1989) Penile response to intracavernosal vasoactive intestinal polypeptide alone and in combination with other vasoactive agents. Br J Urol 64:191–194

    Google Scholar 

  104. Kim N, Azadzoi KM, Goldstein I, Saenz de Tejada I (1991) A nitric oxide-like factor mediates nonadrenergic-noncholinergic neurogenic relaxation of penile corpus cavernosum smooth muscle. J Clin Invest 88:112–118

    Google Scholar 

  105. Kim N, Vardi Y, Padma-Nathan H, Daley J, Goldstein I, Saenz de Tejada I (1992) Oxygen tension regulates erection by modulating nitric oxide production in corpus cavernosum. Int J Impotence Res 4 [Suppl 2]:A3

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

    Google Scholar 

  107. Kimoto Y, Kessler R, Constantinou CE (1990) Endothelium dependent relaxation of human corpus cavernosum by bradykinin. J Urol 144:1015–1017

    Google Scholar 

  108. Kirkeby HJ, Forman A, Sørensen S, Andersson K-E (1989) Effects of noradrenaline, 5-hydroxytryptamine and histamine on human penile cavernous tissue and circumflex veins. Int J Impotence Res 1:181–188

    Google Scholar 

  109. Kirkeby HJ, Jørgensen J, Ottesen B (1991) Neuropeptide Y (NPY) in human penile corpus cavernosum and circumflex veins. J Urol 145:605–609

    Google Scholar 

  110. Kirkeby HJ, Fahrenkrug J, Holmquist F, Ottesen B (1992) Vasoactive intestinal polypeptide (VIP) and peptide histidine methionine (PHM) in human penile corpus cavernosum tissue and circumflex veins: localization and in vitro effects. Eur J Clin Invest 22:24–30

    Google Scholar 

  111. Kirkeby HJ, Svane D, Poulsen J, Tøttrup A, Forman A, Andersson K-E (1993) Role of the l-arginine/nitric oxide pathway in relaxation of isolated human penile cavernous tissue and circumflex veins. Acta Physiol Scand 149:385–392

    Google Scholar 

  112. Klinge E, Sjöstrand NO (1977) Suppression of the excitatory adrenergic neurotransmission; a possible role of cholinergic nerves in the retractor penis muscle. Acta Physiol Scand 100:368–376

    Google Scholar 

  113. Knispel HH, Goessl C, Beckmann R (1991) Basal and acetylcholine-stimulated nitric oxide formation mediates relaxation of rabbit cavernous smooth muscle. J Urol 146:1429–1433

    Google Scholar 

  114. Knispel HH, Goessl C, Beckmann R (1992) Nitric oxide mediates relaxation in rabbit and human corpus cavernosum smooth muscle. Urol Res 20:253–257

    Google Scholar 

  115. Knispel HH, Goessl C, Beckmann R (1992) Nitric oxide mediates neurogenic relaxation induced in rabbit cavernous smooth muscle by eletric field stimulation. Urology 40:471–476

    Google Scholar 

  116. Kohno M, Yasunari K, Murakawa K, Yokokawa K, Horio T, Fukui T, Takeda T (1990) Release of immunoreactive endothelin from porcine aortic strips. Hypertension 15:718–723

    Google Scholar 

  117. Krall JF, Fittinghoff M, Rajfer J (1988) Characterization of cyclic nucleotide and inositol 1,4,5-trisphosphate-sensitive calcium-exchange activity of smooth muscle cells cultured from the human corpora cavernosa. Biol Reprod 39:913–922

    Google Scholar 

  118. Lamano Carvalho TL, Hodson NP, Blank MA, Watson PF, Mulderry PK, Bishop AE, Bloom SR, Polak JM (1986) Occurrence, distribution and origin of peptide-containing nerves of guinea-pig and rat male genitalia and the effects of denervation on sperm characteristics. J Anat 149:121–141

    Google Scholar 

  119. Larsen J-J, Ottesen B, Fahrenkrug J, Fahrenkrug L (1981) Vasoactive intestinal polypeptide (VIP) in the male genitourinary tract, concentration and motor effect. Invest Urol 19:211–213

    Google Scholar 

  120. Lau LC, Adaikan PG, Ratnam SS (1991) Effect of endothelin-1 on the human corpus cavernosum and penile vasculature. Asia Pac J Pharmacol 6:287–292

    Google Scholar 

  121. Lerner SE, Melman A, Christ GJ (1993) A review of erectile dysfunction: new insights and more questions. J Urol 149:1246–1255

    Google Scholar 

  122. Lincoln J, Crowe R, Blackley PF, Pryor JP, Lumley JSP, Burnstock G (1987) Changes in the VIPergic, cholinergic and adrenergic innervation of human penile tissue in diabetic and non-diabetic impotent males. J Urol 137:1053–1059

    Google Scholar 

  123. Lincoln J, Crowe R, Burnstock G (1991) Neuropeptides and impotence. In: Kirby RS, Carson C, Webster GD (eds) Impotence: diagnosis and management of male erectile dysfunction. Butterworth-Heinemann, Oxford, pp 27–31

    Google Scholar 

  124. Lue T, Tanagho E (1987) Physiology of erection and pharmacological management of impotence. J Urol 137:829–836

    Google Scholar 

  125. Lue TF, Takamura T, Schmidt RA, Palubinshos AJ, Tanagho E (1983) Hemodynamics of erection in the monkey. J Urol 130:1237–1241

    Google Scholar 

  126. Marin J, Sánchez-Ferrer CF (1990) Role of endotheliumformed nitric oxide on vascular responses. Gen Pharmacol 21:575–587

    Google Scholar 

  127. Marshall JJ, Kontos HA (1990) Endothelium-derived relaxing factors. A perspective from in vivo data. Hypertension 16:371–386

    Google Scholar 

  128. Martinez-Pineiro L, Trigo-Rocha F, Hsu GL, Heyden B von, Lue TF, Tanagho EA (1993) Cyclic guanosine monophosphate mediates penile erection in the rat. Urol Res 24:492–499

    Google Scholar 

  129. Masaki T, Yaganisawa M, Goto K (1992) Physiology and pharmacology of endothelins. Med Res Rev 12:391–421

    CAS  PubMed  Google Scholar 

  130. Matzuzaka J, Aoki H, Yeh KH, Banya Y, Fuzioka T, Kubo T, Yasuda N (1990) Experimental study of erection ejaculation reflex. Int J Impotence Res 2 [Suppl 2]:15–16

    Google Scholar 

  131. McGrath MA, Shepherd J (1976) Inhibition of adrenergic neurotransmission in canine vascular smooth muscle by histamine: mediation by H2-receptors. Circ Res 39:566–573

    Google Scholar 

  132. Meyhoff HH, Rosenkilde P, Bødker A (1992) Non-invasive management of impotence with trancutaneous nitroglycerin. Br J Urol 69:88–90

    Google Scholar 

  133. Mirone V, Imbimbo C, Palmieri A, Fabrizio F, Lamberti F, Longo N (1992) Intracavernous injection of cGMP in impotent man. Int J Impotence Res 4 [Suppl 2]:p123

    Google Scholar 

  134. Molderings GJ, Ahlen H van, Göthert M (1992) Modulation of noradrenaline release in human corpus cavernosum by presynaptic prostaglandin receptors. Int J Impotence Res 4:19–26

    Google Scholar 

  135. Moncada S, Vane JR (1979) Arachidonic acid metabolites and the interactions between platelets and blood-vessel walls. N Engl J Med 300:1142–1147

    Google Scholar 

  136. Moncada S, Gryglewski R, Bunting S, Vane JR (1976) An enzyme isolated from arteries transforms prostaglandin endoperoxides to an unstable substance that inhibits platelet aggregation. Nature 263:663–665

    Google Scholar 

  137. Moncada S, Palmer RMJ, Higgs EA (1989) Biosynthesis of nitric oxide from L-arginine. Biochem Pharmacol 38:1709–1715

    Google Scholar 

  138. Moreno AP, Campos de Carvalho AC, Christ G, Melman A, Spray DC (1993) Gap junctions between human corpus cavernosum smooth muscle cells: gating properties and unitary conductance. Am J Physiol 264:C80-C92

    Google Scholar 

  139. Moriel EZ, Gonzalez-Cavidad N, Ignarro LJ, Byrns R, Rajfer J (1993) Levels of nitric oxide metabolites do not increase during penile erection. Urology 42:551–553

    Google Scholar 

  140. Nahoum CRD, Hadler WA, Santana CAR (1988) Mast cells, histamine and penile erection. In: Goldstein I (ed) Proceedings of the Third Biennal World Meeting on Impotence. International Society for Impotence Research, Boston, p 43

    Google Scholar 

  141. Nakamura S, Naruse M, Naruse K, Demura H, Uemura H (1990) Immunocytochemical localization of endothelin in cultured bovine endothelial cells. Histochemistry 94:475–477

    Google Scholar 

  142. Ottesen B, Wagner G, Virag R, Fahrenkrug J (1984) Penile erection: possible role for vasoactive intestinal polypeptide as a neurotransmitter. BMJ 288:9–11

    Google Scholar 

  143. Owen JA, Saunders F, Harris C, Fenemore J, Reid K, Surridge D, Condra M, Morales A (1989) Topical nitroglycerin: a potential treatment for impotence. J Urol 141:546–548

    Google Scholar 

  144. Palmer RMJ, Ferrige AG, Moncada S (1987) Nitric oxide release accounts for the biological activity of endothelium-derived relaxing factor. Nature 327:524–526

    Article  CAS  PubMed  Google Scholar 

  145. Pentillä O, Vartiainen A (1964) Acetylcholine, histamine, 5-hydroxytryptamine and catecholamine contents of mammalian penile erectile and urethral tissue. Acta Pharmacol Toxicol 21:145–151

    Google Scholar 

  146. Pickard RS, Powell PH, Zar MA (1991) The effect of inhibitors of nitric oxide biosynthesis and cyclic GMP formation on nerve-evoked relaxation of human cavernosal smooth muscle. Br J Pharmacol 104:755–759

    Google Scholar 

  147. Pickard RS, Zar MA, Powell PH (1992) Nerve-evoked nitric oxide production in cavernosal tissue from potent and impotent men. Int J Impotence Res 4 [Suppl 2]:A2

  148. Pickard RS, Powell PH, Zar MA (1993) Evidence against vasoactive intestinal polypeptide as the relaxant neurotransmitter in human cavernosal smooth muscle. Br J Pharmacol 108:497–500

    Google Scholar 

  149. Polak JM, Gu J, Mina S, Bloom SR (1981) Vipergic nerves in the penis. Lancet II:217–219

    Google Scholar 

  150. Porst H (1989) Prostaglandin E1 bei erektiler Dysfunktion. Urologe 28:94–98

    Google Scholar 

  151. Porst H (1993) Prostaglandin E1 and the nitric oxide donor linsidomine for erectile failure: a diagnostic comparative study of 40 patients. J Urol 149:1280–1293

    Google Scholar 

  152. Price DT, Schwinn DA, Kim JH, Carson CC III, Caron MG, Lefkowitz RJ (1993) Alpha1 adrenergic receptor subtype mRNA expression in human corpus cavernosum (abstract 287). J Urol 149:285A

    Google Scholar 

  153. Rajfer J, Aronson WJ, Bush PA, Dorey FJ, Ignarro LJ (1992) Nitric oxide as a mediator of relaxation of the corpus cavernosum on response to nonadrenergic, noncholinergic neurotransmission. N Engl J Med 326:90–94

    Google Scholar 

  154. Rakugi H, Tabuchi Y, Nakamuru M, Nagano M, Higashimori K, Mikami H, Ogihara T, Suzuki N (1990) Evidence for endothelin-1 release from resistance vessels of rats in response to hypoxia. Biochem Biophys Res Commun 169:973–977

    Google Scholar 

  155. Rasmussen H (1986) The calcium messenger system. N Engl J Med 314:1164–1170

    Google Scholar 

  156. Roy AC, Tan SM, Kottegoda SR, Tatnam SS (1984) Ability of human corpora cavernosa muscle to generate prostaglandins and thromboxanes in vitro. IRCS Med Sci 12:608–609

    Google Scholar 

  157. Roy AC, Adaikan PG, Sen DK, Ratnam SS (1989) Prostaglandin 15-hydroxydehydrogenase activity in human penile corpora cavernosa and its significance in prostaglandin-mediated penile erection. Br J Urol 64:180–182

    Google Scholar 

  158. Roy JB, Petrone RL, Said S (1990) A clinical trial of intracavernous vasoactive intestinal peptide to induce penile erection. J Urol 143:302–304

    Google Scholar 

  159. Saenz de Tejada I, Blanco R, Goldstein I, Azadzoi K, De las Morenas A, Krane RJ, Cohen RA (1988) Cholinergic neurotransmission in human corpus cavernosum. I. Responses of isolated tissue. Am J Physiol 254:H468-H472

    Google Scholar 

  160. Saenz de Tejada I, Carson MP, Traish A, Eastman EH, Goldstein I (1989) Role of endothelin, a novel vasoconstrictor peptide, in the local control of penile smooth muscle. J Urol 141:222A

    Google Scholar 

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

    Google Scholar 

  162. Saenz de Tejada I, Carson MP, De las Morenas A, Goldstein I, Traish AM (1991) Endothelin: localization, synthesis, activity, and receptor types in human penile corpus cavernosum. Am J Physiol 261:H1078-H1085

    Google Scholar 

  163. Sánchez-Ferrer CF, Marin J (1990) Endothelium-derived contractile factors. Gen Pharmacol 21:589–603

    Google Scholar 

  164. Sathananthan AH, Adaikan PG, Lau LC, Ho J, Ratnam SS (1991) Fine structure of the human corpus cavernosum. Arch Androl 26:107–117

    Google Scholar 

  165. Schmalbruch H, Wagner G (1989) Vasoactive intestinal polypeptide (VIP)- and neuropeptide Y (NPY)-containing nerve fibres in the penile cavernous tissue of green monkeys (Cercopithecus aethiops). Cell Tissue Res 256:529–541

    Google Scholar 

  166. Shirai M, Maki A, Takanami M, Ando K, Nakamura K, Yanaihara N, Yanaihara C, Iguchi K, Fujita T, Iwanaga T (1990) Content and distribution of vasoactive intestinal polypeptide (VIP) in cavernous tissues of human penis. Urology 35:360–363

    Google Scholar 

  167. Sjöstrand NO, Klinge E (1979) Principal mechanisms controlling penile retraction and protrusion in rabbits. Acta Physiol Scand 106:199–214

    Google Scholar 

  168. Sokolovsky M (1992) Endothelins and sarafotoxins: physiological regulation, receptor subtypes and transmembrane signaling. Pharmacol Ther 54:129–149

    Google Scholar 

  169. Steers WD, Selby Jr JB (1991) Use of methylene blue and selective embolization of the pudendal artery for high flow priapism refractory to medical and surgical treatments. J Urol 146:1361–1363

    Google Scholar 

  170. Steers WD, McConnell J, Benson GS (1984) Anatomical localization and some pharmacological effects of vasoactive intestinal polypeptide in human and monkey corpus cavernosum. J Urol 132:1048–1093

    Google Scholar 

  171. Stief CG, Benard F, Bosch RJLH, Aboseif SR, Nunes L, Lue T, Tanagho E (1989) Acetylcholine as a possible neurotransmitter in penile erection. J Urol 14:1444–1448

    Google Scholar 

  172. Stief CG, Holmquist F, Allhoff EP, Andersson K-E, Jonas U (1991) Preliminary report on the effect of the nitric oxide (NO) donor SIN-1 on human cavernous tissue in vivo. World J Urol 9:237–239

    Google Scholar 

  173. Stief CG, Wetterauer U, Schaebsdau FH, Jonas U (1991) Calcitonin-gene-related peptide: a possible role in human penile erection and its therapeutic application in impotent patients. J Urol 146:1010–1014

    Google Scholar 

  174. Stief CG, Thon WF, Djamilian M, Allhof EP, Jonas U (1992) Trancutaneous registration of cavernous smooth muscle electrical activity: noninvasive diagnosis of neurogenic autonomic impotence. J Urol 147:47–50

    Google Scholar 

  175. Stief CG, Holmquist F, Djamilian M, Krah H, Andersson K-E, Jonas U (1992) Preliminary results with the nitric oxide donor linsidomine chlorhydrate in the treatment of human erectile dysfunction. J Urol 148:1437–1440

    Google Scholar 

  176. Stief CG, Benard F, Bosch R, Aboseif S, Wetterauer U, Lue TF, Tanagho EA (1993) Calcitonin gene-related peptide: possibly neurotransmitter contributes to penile erection in monkeys. Urology 41:397–401

    Google Scholar 

  177. Taher A, Stief CG, Djamilian M, Jonas U (1992) Effect of SIN1 on isolated human cavernous smooth muscle and influence of various selective phosphodiesterase inhibitors. Int J Impotence Res 4 [Suppl 2]:A9

  178. Taher A, Meyer M, Schulz-Knappe P, Forssmann W, Stief CG, Jonas U (1993) Phosphodiesterase activity in human cavernous tissue and the effect of various selective inhibitors (abstract 285). J Urol 149:285A

    Google Scholar 

  179. Takahashi Y, Aboseif SR, Benard F, Stief CG, Lue TF, Tanagho EA (1992) Effect of intracavernous simultaneous injection of acetylcholine and vasoactive intestinal polypeptide on canine penile erection. J Urol 148:446–448

    Google Scholar 

  180. Takahashi Y, Ishii N, Lue TF, Tanagho EA (1992) Effects of adenosine triphosphate on canine penile erection. Int J Impotence Res 4:27–34

    Google Scholar 

  181. Takahashi Y, Ishii N, Lue TF, Tanagho EA (1992) Effects of adenosine on canine penile erection. J Urol 148:1323–1325

    Google Scholar 

  182. Tong Y-C, Broderick G, Hypolite J, Levin RM (1992) Correlations of purinergic, cholinergic and adrenergic functions in rabbit corporal cavernosal tissue. Pharmacology 45:241–249

    Google Scholar 

  183. Trigo-Rocha F, Aronson WJ, Hohenfellner M, Ignarro LJ, Rajfer LJ, Rajfer J, Lue TF (1993) Nitric oxide and cGMP: mediators of pelvic nerve-stimulated erection in dogs. Am J Physiol 264:H419-H422

    Google Scholar 

  184. Trigo-Rocha F, Hsu GL, Donatucci CF, Lue TF (1993) The role of cyclic adenosine monophosphate, cyclic guanosine monophosphate, endothelium and nonadrenergic, noncholinergic neurotransmission in canine penile erection. J Urol 149:872–877

    Google Scholar 

  185. Trigo-Rocha F, Hsu G-L, Donatucci CF, Martinez-Pineiro L, Lue TF, Tanagho EA (1994) Intracellular mechanism of penile erection in monkeys. Neurourol Urodyn 13:71–80

    Google Scholar 

  186. Virag R, Ottesen B, Fahrenkrug J, Levy C, Wagner G (1982) Vasoactive intestinal polypeptide release during penile erection in man. Lancet II:1166

    Google Scholar 

  187. Wagner G, Brindley GS (1980) The effect of atropine and α-and β-blockers on human penile erection: a controlled pilot study. In: Zorgniotti AW, Rossi G (eds) Vasculogenic impotence. Thomas, Springfield, pp 77–81

    Google Scholar 

  188. Wagner G, Gerstenberg T (1987) Intracavernous injection of vasoactive intestinal polypeptide (VIP) does not induce erection in man per se. World J Urol 5:171–177

    Google Scholar 

  189. Wagner G, Gerstenberg T, Levin RJ (1989) Electrical activity of corpus cavernosum during flaccidity and erection of the human penis: a new diagnostic method? J Urol 142:723–725

    Google Scholar 

  190. Wahlestedt C, Reis DJ (1993) Neuropeptide Y-related peptides and their receptors — are the receptors potential therapeutic drug targets? Annu Rev Pharmacol Toxicol 32:309–352

    Google Scholar 

  191. Wang R, Higuera TR, Sikka SC, Minkes RK, Bellan JA, Kadowitz PJ, Domer FR, Hellstrom WJ (1993) Penile erections induced by vasoactive intestinal peptide and sodium nitroprusside. Urol Res 21:75–78

    Google Scholar 

  192. Wang R, Domer FR, Sikka SC, Kadowitz PJ, Hellstrom WJG (1994) Nitric oxide mediates penile erection in cats. J Urol 151:234–237

    Google Scholar 

  193. Wei M-Q, Wagner G (2601992) Extracellular calcium and contractility of porcine smooth muscle of corpus cavernosum. Int J Impotence Res 4:211–218

    Google Scholar 

  194. Wespes E, Schiffman S, Gilloteaux J, Schulman C, Vierendeels G, Menu R, Pelletier G, Vaudry H, Vanderhaeghen JJ (1988) Study of neuropeptide Y-containing nerve fibers in the human penis. Cell Tissue Res 254:69–74

    Google Scholar 

  195. Willis EA, Ottesen B, Wagner G, Sundler F, Fahrenkrug J (1981) Vasoactive intestinal polypeptide (VIP) as a possible neurotransmitter involved in penile erection. Acta Physiol Scand 113:545–547

    Google Scholar 

  196. Willis EA, Ottesen B, Wagner G, Sundler F, Fahrenkrug J (1983) Vasoactive intestinal polypeptide (VIP) as a putative neurotransmitter in penile erection. Life Sci 33:383–391

    Google Scholar 

  197. Wolfson B, Pickett S, Scott N, Kernion J de, Rajfer J (1992) Intraurethral prostaglandin E-2 cream: an alternative treatment for erectile dysfunction. Int J Impotence Res 4 [Suppl 2]:A101

  198. Wu H-S, Broderick GA, Suh J-K, Hypolite JA, Levin RM (1993) Effects of purines on rabbit corpus cavernosum contractile activity. Int J Impotence Res 5:161–167

    Google Scholar 

  199. Yajima M, Kohno S, Baba K, Komura H, Haraguchi C, Iwamoto T, Osada T (1992) The coexistence of neuropeptide Y and norepinephrine in rabbit corpus cavernosum penis: an in vitro study. Int J Impotence Res 4 [Suppl 1]:9–12

    Google Scholar 

  200. Yanagisawa M, Kurihara H, Kimura S, Tomobe Y, Kobayashi M, Mitsui Y, Yazaki Y, Goto K, Masaki T (1988) A novel potent vasoconstrictor peptide produced by vascular endothelial cells. Nature 332:411–415

    Article  PubMed  Google Scholar 

  201. Yiangou Y, Christofides ND, Gu J, Blank MA, Polak JM, Bloom SR (1985) Peptide histidine methionine (PHM) and the human male genitalia. Neuropeptides 6:133–142

    Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Department of Clinical Pharmacology, University Hospital of Lund, S-22185, Lund, Sweden

    K. -E. Andersson & F. Holmquist

Authors
  1. K. -E. Andersson
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. F. Holmquist
    View author publications

    You can also search for this author in PubMed Google Scholar

Rights and permissions

Reprints and permissions

About this article

Cite this article

Andersson, K.E., Holmquist, F. Regulation of tone in penile cavernous smooth muscle. World J Urol 12, 249–261 (1994). https://doi.org/10.1007/BF00191204

Download citation

  • Issue Date:

  • DOI: https://doi.org/10.1007/BF00191204

Keywords

Search

Navigation