Advertisement

Nitric Oxide and Other Neurotransmitters of the Corpus Cavernosum

  • Nestor F. Gonzalez-Cadavid
  • Jacob Rajfer

Abstract

The physiology of erection comprises three distinct processes acting in concert: (1) increased arterial inflow, (2) active cavernosal smooth-muscle relaxation, and (3) decreased venous outflow. Cavernosal smooth-muscle relaxation appears to be the key event in a normal erection. Therefore, the cavernosal smooth muscle may be the critical site where erectile dysfunction begins.1

Keywords

Nitric Oxide Nitric Oxide Erectile Dysfunction Vasoactive Intestinal Peptide Vasoactive Intestinal Polypeptide 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  1. 1.
    Saenz de Tejada I. Mechanisms for the regulation of penile smooth muscle contractility. In: Lue T, ed. World Book of Impotence. Nishimura, London: Smith Gordon; 1992: 264–292.Google Scholar
  2. 2.
    Moncada S, Higgs A. The L-arginine-nitric oxide pathway. N Engl J Med 1993; 329: 2002–2012.PubMedCrossRefGoogle Scholar
  3. 3.
    Lowenstein CHJ, Dinerman JL, Snyder SH. Nitric oxide: a physiologic messenger. Ann Intern Med 1994; 120: 227–237.PubMedGoogle Scholar
  4. 4.
    Murad F. The nitric oxide-cyclic GMP signal transduction system for intracellular and intercellular communication. Recent Prog Horm Res 1994; 49: 239–248.PubMedGoogle Scholar
  5. 5.
    Forsterman U, Closs EI, Pollock JS, et al. Nitric oxide isozymes. Characterization, purification, molecular cloning and functions. Hypertension 1994; 23: 1121–1131.CrossRefGoogle Scholar
  6. 6.
    Fukuto JM, Chaudhuri G. Inhibition of constitutive and inducible nitric oxide synthase: potential selective inhibition. Annu Rev Pharmacol Ther 1995; 35: 165–194.CrossRefGoogle Scholar
  7. 7.
    Gross SS, Wolin MS. Nitric oxide: pathophysiological mechanisms. Annu Rev Physiol 1995; 57: 737–769.PubMedCrossRefGoogle Scholar
  8. 8.
    Mehta JL. Endothelium, coronary vasodilation, and organic nitrates. Am Heart J 1995; 129: 382–391.PubMedCrossRefGoogle Scholar
  9. 9.
    Umans JG, Levy R. Nitric oxide in the regulation of blood flow and arterial pressure. Annu Rev Physiol 1995; 57: 771–790.PubMedCrossRefGoogle Scholar
  10. 10.
    Rand MJ, Li CG. Nitric oxide as a neurotransmitter in peripheral nerves: nature of transmitter and mechanism of transmission. Annu Rev Physiol 1995; 57: 659–682.PubMedCrossRefGoogle Scholar
  11. 11.
    Zhang J, Snyder SH. Nitric oxide in the nervous system. Annu Rev Pharmacol Toxicol 1995; 35: 213–233.PubMedCrossRefGoogle Scholar
  12. 12.
    Lugg J, Gonzalez-Cadavid NF, Rajfer J. The role of nitric oxide in erectile function. J Androl 1995; 16: 2–6.PubMedGoogle Scholar
  13. 13.
    Giuliano FA, Rampin O, Benoit G, et al. Neural control of penile erection. Urol Clin North Am 1995; 22: 747–766.PubMedGoogle Scholar
  14. 14.
    Burnett AL. Role of nitric oxide in the physiology of erection. Biol Reprod 1995; 52: 485–489.PubMedCrossRefGoogle Scholar
  15. 15.
    Burnett AL. Nitric oxide control of lower genitourinary tract functions: a review. Urology 1995; 45: 1071–1083.PubMedCrossRefGoogle Scholar
  16. 16.
    Ignarro LJ, Bush PA, Buga GM, et al. Nitric oxide and cyclic GMP formation upon electric field stimulation cause relaxation of corpus cavernosum smooth muscle. Biochem Biophys Res Commun 1990; 170: 843–850.PubMedCrossRefGoogle Scholar
  17. 17.
    Knispel HH, Goessl C, Beckmann R. Basal and acetylcholine-stimulated nitric oxide formation mediates relaxation of rabbit cavernous smooth muscle. J Urol 1991; 146: 1429–1433.PubMedGoogle Scholar
  18. 18.
    Kim N, Azadzoi KM, Golstein I, et al. A nitric oxide-like factor mediates nonadrenergicnoncholinergic neurogenic relaxation of penile corpus cavernosum smooth muscle. J Clin Invest 1991; 88: 112–118.PubMedCrossRefGoogle Scholar
  19. 19.
    Pickard RS, Powell PH, Zar MA. The effect of inhibitors of nitric oxide biosynthesis and cyclic GMP formation on nerve-evoked relaxation of human cavernosal smooth muscle. Br J Pharmacol 1991; 104: 755–759.PubMedCrossRefGoogle Scholar
  20. 20.
    Holmquist F, Hedlund H, Andersson KE. LN°-nitro arginine inhibits non-adrenergic, noncholinergic relaxation of human isolated corpus cavernosum. Acta Physiol Scand 1991; 141: 441–442.PubMedCrossRefGoogle Scholar
  21. 21.
    Rajfer J, Aronson WJ, Bush PA, et al. Nitric oxide as a mediator of relaxation of the corpus cavernosum in response to nonadrenergic, noncholinergic neurotransmission. N Engl J Med 1992; 326: 90–94.PubMedCrossRefGoogle Scholar
  22. 22.
    Bush PA, Aronson WJ, Buga GM, et al. Nitric oxide is a potent relaxant of human and rabbit corpus cavernosum. J Urol 1992; 147: 1650–1655.PubMedGoogle Scholar
  23. 23.
    Azadzoi KM, Kim N, Brown ML, et al. Endothelium-derived nitric oxide and cyclooxygenase products modulate corpus cavernosum smooth muscle tone. J Urol 1992; 147: 220–225.PubMedGoogle Scholar
  24. 24.
    Knispel HH, Goessl C, Beckmann R. Nitric oxide mediates neurogenic relaxation induced in rabbit cavernous smooth muscle by electric field stimulation. Urology 1992; 40: 471–476.PubMedCrossRefGoogle Scholar
  25. 25.
    Knispel HH, Goessl C, Beckmann R. Nitric oxide mediates relaxation in rabbit and human corpus cavernosum smooth muscle. Urol Res 1992; 20: 253–257.PubMedCrossRefGoogle Scholar
  26. 26.
    Kirkeby HJ, Svane D, Poulsen J, et al. 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.PubMedCrossRefGoogle Scholar
  27. 27.
    Holmquist F, Fridstrand M, Hedlund H, et al. Actions of 3-morpholinsidomine (SIN-1) on rabbit isolated penile erectile tissue. J Urol 1993; 150: 1310–1315.PubMedGoogle Scholar
  28. 28.
    Hedlund P, Holmquist F, Hedlund H, et al. Effects of nicorandil on human isolated corpus cavernosum and cavernous artery. J Urol 1994; 151: 1107–1113.PubMedGoogle Scholar
  29. 29.
    Chen X, Lee TJ. Ginsenosides-induced nitric oxide-mediated relaxation of the rabbit corpus cavernosum. Br J Pharmacol 1995; 115: 15–18.PubMedCrossRefGoogle Scholar
  30. 30.
    Levin RM, Hypolite J, Broderick GA. Comparative studies on rabbit corpus cavernosal contraction and relaxation. An in vitro study. J Androl 1994; 15: 36–40.PubMedGoogle Scholar
  31. 31.
    Hayashida H, Okamura T, Tomoyoshi T, et al. Neurogenic nitric oxide mediates relaxation of canine corpus cavernosum. J Urol 1966; 155: 1122–1127.CrossRefGoogle Scholar
  32. 32.
    Holmquist F, Stief CG, Jonas U, et al. Effects of the nitric oxide synthase inhibitor NG-nitro-Larginine on the erectile response to cavernous nerve stimulation in the rabbit. Acta Physiol Scand 1991; 143: 299–304.PubMedCrossRefGoogle Scholar
  33. 33.
    Quinlan DM, Nelson RJ, Partin AW, et al. The rat as a model for the study of penile erection. J Urol 1989; 141: 656–661.PubMedGoogle Scholar
  34. 34.
    Burnett AL, Lowenstein CJ, Bredt D, et al. Nitric oxide: a physiologic mediator of penile erection. Science 1992; 257: 401–403.PubMedCrossRefGoogle Scholar
  35. 35.
    Mills TM, Wiedmeier VT, Stopper VS. Androgen maintenance of erectile function in the rat penis. Biol Reprod 1992; 46: 3424–3428.CrossRefGoogle Scholar
  36. 36.
    Martinez-Pineiro L, Trigo-Rocha F, Hsu GL, et al. Cyclic guanosine monophosphate mediates penile erection in the rat. Eur Urol 1993; 24: 492–499.PubMedGoogle Scholar
  37. 37.
    Finberg JP, Levy S, Vardi Y. Inhibition of nerve stimulation-induced vasodilatation in corpora cavernosa of the pithed rat by blockade of nitric oxide synthase. Br J Pharmacol 1993; 108: 1038–1042.PubMedCrossRefGoogle Scholar
  38. 38.
    Garban H, Vernet D, Freedman A, et al. Effect of aging on nitric oxide-mediated penile erection in the rat. Am J Physiol 1995; 268: H467 - H475.PubMedGoogle Scholar
  39. 39.
    Garban H, Marquez D, Cai L, et al. Restoration of normal penile erectile response in aged rats by long-term treatment with androgens. Biol Reprod 1995; 53: 1365–1372.PubMedCrossRefGoogle Scholar
  40. 40.
    Martinez-Piíeiro L, Brock G, Trigo Rocha F, et al. Rat model for the study of penile erection: pharmacologic and electrical stimulation parameters. Eur Urol 1994; 25: 62–70.Google Scholar
  41. 41.
    Giuliano F, Bernabe J, Jardin A, et al. Antierectile role of the sympathetic nervous system in rats. J Urol 1993; 150: 519–524.PubMedGoogle Scholar
  42. 42.
    Trigo-Rocha F, Aronson WJ, Hohenfellner M, et al. Nitric oxide and cGMP: mediators of pelvic nerve-stimulated erection in dogs. Am J Physiol 1993; 264: H419 - H422.PubMedGoogle Scholar
  43. 43.
    Trigo-Rocha F, Hsu GL, Donatucci CF, et al. The role of cyclic adenosine monophosphate, cyclic guanosine monophosphate, endothelium and nonadrenergic, noncholinergic neurotransmission in canine penile erection. J Urol 1993; 149: 872–877.PubMedGoogle Scholar
  44. 44.
    Wang R, Domer FR, Sikka SC, et al. Nitric oxide mediates penile erection in cats. J Urol 1994; 151: 234–237.PubMedGoogle Scholar
  45. 45.
    Heaton JPW, Varrin SJ, Morales A. The characterization of a bioassay of erectile function in a rat model. J Urol 1991; 145: 1099–1102.PubMedGoogle Scholar
  46. 46.
    Melis MR, Argiolas A. Nitric oxide synthase inhibitors prevent apomorphine-and oxytocin-induced penile erection and yawning in male rats. Brain Res Bull 1993; 32: 71–74.PubMedCrossRefGoogle Scholar
  47. 47.
    Melis MR, Stancampiano R, Argiolas A. Nitric oxide synthase inhibitors prevent N-methylD-aspartic acid-induced penile erection and yawning in male rats. Neurosci Lett 1994; 179: 912.CrossRefGoogle Scholar
  48. 48.
    Paick J-S, Lee SW. The neural mechanism of apomorphine-induced erection: an experimental study by comparison with electrostimulation-induced erection in the rat model. J Urol 1994; 152: 2125–2128.PubMedGoogle Scholar
  49. 49.
    Hull EM, Lumley LA, Matuszewich L, et al. The roles of nitric oxide in sexual function of male rats. Neuropharmacology 1994; 33: 1499–1504.PubMedCrossRefGoogle Scholar
  50. 50.
    Bush PA, Gonzalez NE, Ignarro LJ. Biosynthesis of nitric oxide and citrulline from L-arginine by constitutive nitric oxide synthase present in rabbit corpus cavernosum. Biochem Biophys Res Commun 1992; 186: 308–314.PubMedCrossRefGoogle Scholar
  51. 51.
    Keast JR. A possible neural source of nitric oxide in the rat penis. Neurosci Lett 1992; 143: 69–73.PubMedCrossRefGoogle Scholar
  52. 52.
    McNeill DL, Papka RE, Harris CH. CGRP immunoreactivity and NADPH-diaphorase in afferent nerves of the rat penis. Peptides 1992; 13: 1239–1246.PubMedCrossRefGoogle Scholar
  53. 53.
    Alm P, Larsson B, Ekblad E, et al. Immunohistochemical localization of peripheral nitric oxide synthase-containing nerves using antibodies raised against synthesized C- and N-terminal fragments of a cloned enzyme from rat brain. Acta Physiol Scand 1993; 148: 421–429.PubMedCrossRefGoogle Scholar
  54. 54.
    Vizzard MA, Erdman SL, Forstermann U, et al. Differential distribution of nitric oxide synthase in neural pathways to the urogenital organs (urethra, penis, urinary bladder) of the rat. Brain Res 1994; 646: 279–291.PubMedCrossRefGoogle Scholar
  55. 55.
    Ding YQ, Wang YQ, Qin BZ, et al. The major pelvic ganglion is the main source of nitric oxide synthase-containing nerve fibers in penile erectile tissue of the rat. Neurosci Lett 1993; 164: 187–189.PubMedCrossRefGoogle Scholar
  56. 56.
    Schirar A, Giuliano F, Rampin O, et al. A large proportion of pelvic neurons innervating the corpora cavernosa of the rat penis exhibit NADPH-diaphorase activity. Cell Tissue Res 1994; 278: 517–525.PubMedCrossRefGoogle Scholar
  57. 57.
    Domoto T, Tsumori T. Co-localization of nitric oxide synthase and vasoactive intestinal peptide immunoreactivity in neurons of the major pelvic ganglion projecting to the rat rectum and penis. Cell Tissue Res 1994; 278: 273–278.PubMedCrossRefGoogle Scholar
  58. 58.
    Ding YQ, Takada M, Kaneko T, et al. Colocalization of vasoactive intestinal polypeptide and nitric oxide in penis-innervating neurons in the major pelvic ganglion of the rat. Neurosci Res 1995; 22: 129–131.PubMedCrossRefGoogle Scholar
  59. 59.
    Burnett AL, Saito S, Maguire MP, et al. Localization of nitric oxide synthase in spinal nuclei innervating pelvic ganglia. J Urol 1995; 153: 212–217.PubMedCrossRefGoogle Scholar
  60. 60.
    Carrier S, Zvara P, Nunes L, et al. Regeneration of nitric oxide synthase-containing nerves after cavernous nerve neurotomy in the rat. J Urol 1995; 153: 1722–1727.PubMedCrossRefGoogle Scholar
  61. 61.
    Burnett AL, Tillman SL, Chang TS, et al. Immunohistochemical localization of nitric oxide synthase in the autonomic innervation of the human penis. J Urol 1993; 150: 73–76.PubMedGoogle Scholar
  62. 62.
    Leone AM, Wiklund NP, Hokfelt T, et al. Release of nitric oxide by nerve stimulation in the human urogenital tract. Neuroreport 1994; 5: 733–736.PubMedCrossRefGoogle Scholar
  63. 63.
    Brock G, Nunes L, Padma-Nathan H, et al. Nitric oxide synthase: a new diagnostic tool for neurogenic impotence. Urology 1993; 42: 412–417.PubMedCrossRefGoogle Scholar
  64. 64.
    Tamura M, Kagawa S, Kimura K, et al. Coexistence of nitric oxide synthase, tyrosine hydroxylase and vasoactive intestinal polypeptide in human penile tissue. A triple histochemical and immunohistochemical study. J Urol 1995; 153: 530–534.PubMedCrossRefGoogle Scholar
  65. 65.
    Jen PYP, Dixon JS, Gearhart JP, et al. Nitric oxide synthase and tyrosine hydroxylase are colocalized in nerves supplying the postnatal human male genitourinary organs. J Urol 1966; 155: 1117–1121.CrossRefGoogle Scholar
  66. 66.
    Bredt DS, Snyder SH. Nitric oxide mediates glutamate-linked enhancement of cGMP levels in the cerebellum. Proc Natl Acad Sci USA 1989; 86: 9030–9033.PubMedCrossRefGoogle Scholar
  67. 67.
    Lugg J, Rajfer J, Gonzalez-Cadavid NF. Dihydrotestosterone is the active androgen in the maintenance of nitric oxide mediated penile erection in the rat. Endocrinology 1995; 136: 1495–1501.PubMedCrossRefGoogle Scholar
  68. 68.
    Vernet D, Cai L, Garban H, et al. Reduction of penile nitric oxide synthase in diabetic BB/ WORdP (type I) and BBZ/WORdP (type II) rats with erectile dysfunction. Endocrinology 1995; 136: 5709–5717.PubMedCrossRefGoogle Scholar
  69. 69.
    Lugg J, Ng Ch, Rajfer J, et al. Cavernosal nerve stimulation reverses castration-induced decrease in rat penile nitric oxide synthase activity. Am J Physiol 1996; 271: 354–361.Google Scholar
  70. 70.
    Penson DF, Ng Ch, Cai L, et al. Androgen dependence of neuronal nitric oxide synthase content and erectile function in the rat penis. In: Stamler J, Gross S, Moncada S, Higgs AE, eds. The Biology of Nitric Oxide. London: Portland Press; 1996.Google Scholar
  71. 71.
    Penson DF, Ng Ch, Cai L, et al. Androgen and pituitary control of penile nitric oxide synthase and erectile function in the rat. Biol Reprod 1996; 55: 567–574.PubMedCrossRefGoogle Scholar
  72. 72.
    Xie Y, Garban H, Ng Ch, et al. Effect of longterm passive smoking on erectile function and penile nitric oxide synthase in the rat. J Urol 1996.Google Scholar
  73. 73.
    Penson DF, Ng Ch, Rajfer J, et al. Adrenal control of erectile function and nitric oxide synthase in the rat penis. J Urol 1996; 155: 617A (#1224).Google Scholar
  74. 74.
    Garban H, Murray FT, Said SI, et al. Normal erectile response to cavernosal nerve stimulation in diabetic BB rats with decreased penile nitric oxide synthase (NOS). 10th International Congress on Endocrinology, San Francisco, CA, 1996: 1–189.Google Scholar
  75. 75.
    Cai L, Murray FT, Rajfer J, et al. Glucose regulates the in vitro content of NOS isoforms in rat penile and pelvic plexus tissue. 10th International Congress on Endocrinology, San Francisco, CA, 1996: 3–854.Google Scholar
  76. 76.
    Chamness SL, Ricker JK, Crone CL, et al. The effect of androgen on nitric oxide synthase in the male reproductive tract of the rat. Fertil Steril 1995; 63: 1101–1107.PubMedGoogle Scholar
  77. 77.
    Hung A, Vernet D, Rajavashisth T, et al. Expression of the inducible nitric oxide synthase in smooth muscle cells from the rat penile corpora cavernosa. J Androl 1995; 16: 469–481.PubMedGoogle Scholar
  78. 78.
    Huang PL, Dawson TM, Bredt DS, et al. Targeted disruption of the neuronal nitric oxide synthase gene. Cell 1993; 75: 1273–1286.PubMedCrossRefGoogle Scholar
  79. 79.
    Nelson RJ, Demas GE, Huang PL, et al. Behavioral abnormalities in male mice lacking neuronal nitric oxide synthase. Nature 1995; 378: 383–386.PubMedCrossRefGoogle Scholar
  80. 80.
    Huang PL, Huang Z, Mashimo H, et al. Hypertension in mice lacking the gene for endothelial nitric oxide synthase. Nature 1995; 377: 239–242.PubMedCrossRefGoogle Scholar
  81. 81.
    Wei X-Q, Charles IG, Smith A, et al. Altered immune responses in mice lacking inducible nitric oxide synthase. Nature 1995; 375: 408–411.PubMedCrossRefGoogle Scholar
  82. 82.
    MacMicking JD, Nathan C, Horn G, et al. Altered responses to bacterial infection and endotoxic shock in mice lacking inducible nitric oxide synthase. Cell 1995; 81: 641–650.PubMedCrossRefGoogle Scholar
  83. 83.
    Snyder SH. No endothelial NO. Nature 1995; 377: 196–197.PubMedCrossRefGoogle Scholar
  84. 84.
    O’Dell TJ, Huang PL, Dawson TM, et al. Endothelial NOS and the blockade of LTP by NOS inhibitors in mice lacking neuronal NOS. Science 1994; 265: 542–546.PubMedCrossRefGoogle Scholar
  85. 85.
    Mills TM, Stopper VS, Wiedmeier VT. Effects of castration and androgen replacement on the hemodynamics of penile erection in the rat. Biol Reprod 1994; 51: 234–238.PubMedCrossRefGoogle Scholar
  86. 86.
    Heaton JPW, Varrin SJ. Effects of castration and exogenous testosterone supplementation in an animal model of penile erection. J Urol 1994; 151: 797–803.PubMedGoogle Scholar
  87. 87.
    Gonzalez-Cadavid NF, Rajfer J. Androgen receptors and penile growth during sexual maturation. In: Hussmann DA, ed. Dialogues in Pediatric Urology, 1996: 19: 4–8.Google Scholar
  88. 88.
    Moody JA, Vernet D, Rajfer J, Gonzalez-Cadavid NF. Effects of the long-term oral administration of L-arginine on the rat erectile response. J Urol 1997 (abstract), in press.Google Scholar
  89. 89.
    Kim N, Vardi Y, Padma-Nathan H, et al. Oxygen tension regulates the nitric oxide pathway. Physiological role in penile erection. J Clin Invest 1993; 91: 437–442.PubMedCrossRefGoogle Scholar
  90. 90.
    Kim NN, Kim JJ, Hypolite J, et al. Altered contractibility of rabbit penile corpus cavernosum smooth muscle by hypoxia. J Urol 1996; 155: 772–778.PubMedCrossRefGoogle Scholar
  91. 91.
    Elabbady AA, Gagnon C, Hassouna MM, et al. Diabetes mellitus increases nitric oxide synthase in penises but not in major pelvic ganglia of rats. Br J Urol 1995; 76: 196–202.PubMedCrossRefGoogle Scholar
  92. 92.
    Carrier S, Hricak H, Lee SS, et al. Radiation-induced decrease in nitric oxide synthase-containing nerves in the rat penis. Radiology 1995; 195: 95–99.PubMedGoogle Scholar
  93. 93.
    Turner J, McLennan PL, Abeywardena MY, et al. Absence of coronary or aortic atherosclerosis in rats having dietary lipid modified vulnerability to cardiac arrhythmias. Atherosclerosis 1990; 82: 105–112.PubMedCrossRefGoogle Scholar
  94. 94.
    Moody JA, Penson DF, Rajfer J, et al. Augmented erectile response to cavernosal nerve stimulation in the spontaneously hypertensive rat. J Urol,1996: 618A, #1229.Google Scholar
  95. 95.
    Schaad NC, Vanacek J, Schulz PE. Photoneural regulation of rat pineal nitric oxide synthase. J Neurochem 1994; 62: 2496–2499.PubMedCrossRefGoogle Scholar
  96. 96.
    Verge VMK, Xu Z, Xu X-J, et al. Marked increase in nitric oxide synthase mRNA in rat dorsal root ganglia after peripheral axotomy: in situ hybridization and functional studies. Proc Natl Acad Sci USA 1994; 89: 11617–11621.CrossRefGoogle Scholar
  97. 97.
    Moriel EZ, González-Cadavid NF, Ignarro LJ, et al. Serum levels of nitric oxide metabolites do not increase during penile erection. Urology 1993; 42: 551–554.PubMedCrossRefGoogle Scholar
  98. 98.
    Ottessen B, Fahrenkrug J. Vasoactive intestinal polypeptide and other preprovasoactive intestinal polypeptide-derived peptides in the female and male genital tract: localization, biosynthesis, and functional and clinical significance. Am J Obstet Gynecol 1995; 172: 1615–1631.CrossRefGoogle Scholar
  99. 99.
    Hauser-Kronberger C, Hacker GW, Graf AH, et al. Neuropeptides in the human penis: an immunohistochemical study. J Androl 1994; 15: 510–520.PubMedGoogle Scholar
  100. 100.
    Miller MA, Morgan RI, Thompson CS, et al. Effects of papaverine and vasointestinal polypeptide on penile and vascular cAMP and cGMP in control and diabetic animals: an in vitro study. Int J Impot Res 1995; 7: 91–100.PubMedGoogle Scholar
  101. 101.
    Yeh KH, Aoki H, Matsuzaka J, et al. Participation of vasoactive intestinal polypeptide (VIP) as a humoral mediator in the erectile response of canine corpus cavernosum penis. J Androl 1994; 15: 187–193.PubMedGoogle Scholar
  102. 102.
    Takahashi Y, Aboseif SR, Benard F, et al. Effect of intracavernous simultaneous injection of acetylcholine and vasoactive intestinal polypeptide on canine penile erection. J Urol 1992; 148: 446–448.PubMedGoogle Scholar
  103. 103.
    Gerstenberg TC, Metz P, Ottesen B, et al. Intracavernous self-injection with vasoactive intestinal polypeptide and phentolamine in the management of erectile failure. J Urol 1992; 147: 1277–1279.PubMedGoogle Scholar
  104. 104.
    Wang R, Higuera TR, Sikka SC, et al. Penile erections induced by vasoactive intestinal peptide and sodium nitroprusside. Urol Res 1993; 21: 75–78.PubMedCrossRefGoogle Scholar
  105. 105.
    Pickard RS, Powell PH, Zar MA. Evidence against vasoactive intestinal polypeptide as the relaxant neurotransmitter in human cavernosal smooth muscle. Br J Pharmacol 1993; 108: 497–500.PubMedCrossRefGoogle Scholar
  106. 106.
    McNeill DL, Papka RE, Harris CH. CGRP immunoreactivity and NADPH-diaphorase in afferent nerves of the rat penis. Peptides 1992; 13: 1239–1246.PubMedCrossRefGoogle Scholar
  107. 107.
    Stief CG, Benard F, Bosch R, et al. Calcitonin gene-related peptide: possibly neurotransmitter contributes to penile erection in monkeys. Urology 1993; 41: 397–401.PubMedCrossRefGoogle Scholar
  108. 108.
    Djamilian M, Stief CG, Kuczyk M, et al. Follow-up results of a combination of calcitonin gene-related peptide and prostaglandin E, in the treatment of erectile dysfunction. J Urol 1993; 149: 1296–1298.PubMedGoogle Scholar
  109. 109.
    Truss MC, Becker AJ, Thon WF, et al. Intracavernous calcitonin gene-related peptide plus prostaglandin E1: possible alternative to penile implants in selected patients. Eur Urol 1994; 26: 40–45.PubMedGoogle Scholar
  110. 110.
    Mombouli J-V, Vanhoutte PM. Kinins and endothelial control of vascular smooth muscle. Annu Rev Pharmacol Toxicol 1995; 35: 679–705.PubMedCrossRefGoogle Scholar
  111. 111.
    Saenz de Tejada I. Commentary on mechanisms for the regulation of the penile smooth muscle contractility. J. Urol 1995; 153: 1762.CrossRefGoogle Scholar
  112. 112.
    Bell CR, Sullivan ME, Dashwood MR, et al. The density and distribution of endothelin 1 and endothelin receptor subtypes in normal and diabetic rat corpus cavernosum. Br J Urol 1995; 76: 203–207.PubMedCrossRefGoogle Scholar
  113. 113.
    Christ GJ, Lerner SE, Kim DC, et al. Endothelin-1 as a putative modulator of erectile dysfunction: I. Characteristics of contraction of isolated corporal tissue strips. J Urol 1995; 153: 1998–2003.PubMedCrossRefGoogle Scholar
  114. 114.
    Traish AM, Netsuwan N, Daley J, et al. A heterogeneous population of cd adrenergic receptors mediates contraction of human corpus cavernosum smooth muscle to norepinephrine. J Urol 1995; 153: 222–227.PubMedCrossRefGoogle Scholar
  115. 115.
    Stief CG, Holmquist F, Djamilian M, et al. Preliminary results with the nitric oxide donor linsidomine chlorhydrate in the treatment of human erectile dysfunction. J Urol 1992; 148: 1437–1440.PubMedGoogle Scholar
  116. 116.
    Truss MC, Becker AJ, Djamilian MH, et al. Role of the nitric oxide donor linsidomine chlorhydrate (SIN-1) in the diagnosis and treatment of erectile dysfunction. Urology 1994; 44: 553–556.PubMedCrossRefGoogle Scholar
  117. 117.
    Wegner H, Knispel HH. Effect of nitric oxide donor, linsidomine chlorhydrate, in treatment of human erectile dysfunction caused by venous leakage. Urology 1993; 42: 409–411.PubMedCrossRefGoogle Scholar
  118. 118.
    Porst H. Prostaglandin E, and the nitric oxide donor linsidomine for erectile failure: a diagnostic comparative study of 40 patients. J Urol 1993; 149: 1280–1283.PubMedGoogle Scholar
  119. 119.
    Brock G, Breza J, Lue TF. Intracavernous sodium nitroprusside: inappropiate impotence treatment. J Urol 1993; 150: 864–867.PubMedGoogle Scholar
  120. 120.
    Martinez-Pineiro L, Lopez-Tello J, Alonso Dorrego JM, et al. Preliminary results of a comparative study with intracavernous sodium nitroprusside and prostaglandin E, in patients with erectile dysfunction. J Urol 1995; 153: 1487–1490.PubMedCrossRefGoogle Scholar
  121. 121.
    Hellstrom WJ, Monga M, Wang R, et al. Penile erection in the primate: induction with nitric-oxide donors. J Urol 1994; 151: 1723–1727.PubMedGoogle Scholar
  122. 122.
    Trigo-Rocha F, Hsu GL, Donatucci CF, et al. Intracellular mechanism of penile erection in monkeys. Neurourol Urodynam 1994; 13: 71–80.CrossRefGoogle Scholar
  123. 123.
    Trigo-Rocha F, Martinez-Pineiro L, Donatucci CF, et al. Sodium nitroprusside: physiologic effects as a nitric oxide donor in three species. Int J Impot Res 1995; 7: 49–56.PubMedGoogle Scholar
  124. 124.
    Mirone V, Palmieri A, Nistico G. Intracavernous cyclic GMP produces penile erection in patients with erectile dysfunction [letter]. Br J Urol 1993; 71: 365.PubMedGoogle Scholar

Copyright information

© Springer Science+Business Media New York 1997

Authors and Affiliations

  • Nestor F. Gonzalez-Cadavid
  • Jacob Rajfer

There are no affiliations available

Personalised recommendations