Skip to main content
PMC home page
British Journal of Pharmacology logoLink to British Journal of Pharmacology
. 1995 Nov;116(5):2517–2523. doi: 10.1111/j.1476-5381.1995.tb15104.x

Nitric oxide synthase in dog urethra: a histochemical and pharmacological analysis.

M Takeda 1, H Lepor 1
PMCID: PMC1909067  PMID: 8581293

Abstract

1. To examine the presence of nitric oxide synthase (NOS) activity in female dog urethra, pharmacological experiments were performed using electrical field stimulation (EFS), guanethidine, atropine, NG-nitro-L-arginine methyl ester and L-arginine, NOS immunohistochemistry using specific anti-NOS antibody, and reduced nicotinamide adenine dinucleotide phosphate (NADPH) diaphorase staining were also performed. 2. EFS caused frequency-dependent contractions in all urethral preparations, but in the presence of guanethidine and atropine, EFS caused significant relaxation in the proximal urethra and was without effect on the distal urethra. 3. In the presence of guanethidine, atropine, and NG-nitro-L-arginine methyl ester, small contractions to EFS were re-established in the proximal urethra, but not in the distal urethra. NG-nitro-D-arginine methyl ester had no such effect. 4. In the presence of guanethidine, atropine, and NG-nitro-L-arginine methyl ester, the addition of L-arginine, restored the EFS-elicited relaxant responses previously seen with guanethidine and atropine alone in the proximal urethra (at 30 Hz; 12.89 +/- 5.27% to -2.44 +/- 4.43%, mean +/- s.e., P < 0.05). D-Arginine had no such effect. 5. In the distal urethra, the addition of NG-nitro-L-arginine methyl ester and then L-arginine had no effect on responses to EFS in preparations treated with guanethidine and atropine. 6. Sodium nitroprusside caused relaxation in both the proximal and distal urethra. The relaxant responses per cm2 cross sectional area in the proximal and distal urethra were 1.23 +/- 0.29, and 2.02 +/- 0.54 g cm-2 cross sectional area (mean +/- s.e.), respectively: there was no significant difference between them. 7. Both NOS and NADPH diaphorase-positive neurones were present in dog urethra, the densities of both being higher in the proximal urethra than in the distal urethra. 8. These results show that female dog urethra possesses NOS nerves and that endogenous NO may play a role in relaxation in the proximal but not the distal urethra.

Full text

PDF
2517

Images in this article

2521Figure 5
on p.2521
2521Figure 6
on p.2521
2522Figure 7
on p.2522

Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Andersson K. E., Garcia Pascual A., Persson K., Forman A., Tøttrup A. Electrically-induced, nerve-mediated relaxation of rabbit urethra involves nitric oxide. J Urol. 1992 Jan;147(1):253–259. doi: 10.1016/s0022-5347(17)37208-7. [DOI] [PubMed] [Google Scholar]
  2. Andersson K. E., Mattiasson A., Sjögren C. Electrically induced relaxation of the noradrenaline contracted isolated urethra from rabbit and man. J Urol. 1983 Jan;129(1):210–214. doi: 10.1016/s0022-5347(17)51986-2. [DOI] [PubMed] [Google Scholar]
  3. Bredt D. S., Hwang P. M., Glatt C. E., Lowenstein C., Reed R. R., Snyder S. H. Cloned and expressed nitric oxide synthase structurally resembles cytochrome P-450 reductase. Nature. 1991 Jun 27;351(6329):714–718. doi: 10.1038/351714a0. [DOI] [PubMed] [Google Scholar]
  4. Bredt D. S., Snyder S. H. Isolation of nitric oxide synthetase, a calmodulin-requiring enzyme. Proc Natl Acad Sci U S A. 1990 Jan;87(2):682–685. doi: 10.1073/pnas.87.2.682. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. Bredt D. S., Snyder S. H. Nitric oxide mediates glutamate-linked enhancement of cGMP levels in the cerebellum. Proc Natl Acad Sci U S A. 1989 Nov;86(22):9030–9033. doi: 10.1073/pnas.86.22.9030. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. Bult H., Boeckxstaens G. E., Pelckmans P. A., Jordaens F. H., Van Maercke Y. M., Herman A. G. Nitric oxide as an inhibitory non-adrenergic non-cholinergic neurotransmitter. Nature. 1990 May 24;345(6273):346–347. doi: 10.1038/345346a0. [DOI] [PubMed] [Google Scholar]
  7. Burnett A. L., Lowenstein C. J., Bredt D. S., Chang T. S., Snyder S. H. Nitric oxide: a physiologic mediator of penile erection. Science. 1992 Jul 17;257(5068):401–403. doi: 10.1126/science.1378650. [DOI] [PubMed] [Google Scholar]
  8. Burnett A. L., Tillman S. L., Chang T. S., Epstein J. I., Lowenstein C. J., Bredt D. S., Snyder S. H., Walsh P. C. Immunohistochemical localization of nitric oxide synthase in the autonomic innervation of the human penis. J Urol. 1993 Jul;150(1):73–76. doi: 10.1016/s0022-5347(17)35401-0. [DOI] [PubMed] [Google Scholar]
  9. Crowe R., Burnstock G. A histochemical and immunohistochemical study of the autonomic innervation of the lower urinary tract of the female pig. Is the pig a good model for the human bladder and urethra? J Urol. 1989 Feb;141(2):414–422. doi: 10.1016/s0022-5347(17)40785-3. [DOI] [PubMed] [Google Scholar]
  10. Garcia-Pascual A., Costa G., Garcia-Sacristan A., Andersson K. E. Relaxation of sheep urethral muscle induced by electrical stimulation of nerves: involvement of nitric oxide. Acta Physiol Scand. 1991 Apr;141(4):531–539. doi: 10.1111/j.1748-1716.1991.tb09114.x. [DOI] [PubMed] [Google Scholar]
  11. Gu J., Blank M. A., Huang W. M., Islam K. N., McGregor G. P., Christofides N., Allen J. M., Bloom S. R., Polak J. M. Peptide-containing nerves in human urinary bladder. Urology. 1984 Oct;24(4):353–357. doi: 10.1016/0090-4295(84)90209-7. [DOI] [PubMed] [Google Scholar]
  12. Hashimoto S., Kigoshi S., Muramatsu I. Nitric oxide-dependent and -independent neurogenic relaxation of isolated dog urethra. Eur J Pharmacol. 1993 Feb 9;231(2):209–214. doi: 10.1016/0014-2999(93)90451-m. [DOI] [PubMed] [Google Scholar]
  13. Heidler H., Casper F., Thüroff J. W. Role of striated sphincter muscle in urethral closure under stress conditions: an experimental study. Urol Int. 1987;42(3):195–200. doi: 10.1159/000281894. [DOI] [PubMed] [Google Scholar]
  14. Holmquist F., Hedlund H., Andersson K. E. L-NG-nitro arginine inhibits non-adrenergic, non-cholinergic relaxation of human isolated corpus cavernosum. Acta Physiol Scand. 1991 Mar;141(3):441–442. doi: 10.1111/j.1748-1716.1991.tb09103.x. [DOI] [PubMed] [Google Scholar]
  15. Knowles R. G., Palacios M., Palmer R. M., Moncada S. Formation of nitric oxide from L-arginine in the central nervous system: a transduction mechanism for stimulation of the soluble guanylate cyclase. Proc Natl Acad Sci U S A. 1989 Jul;86(13):5159–5162. doi: 10.1073/pnas.86.13.5159. [DOI] [PMC free article] [PubMed] [Google Scholar]
  16. Li C. G., Rand M. J. Evidence for a role of nitric oxide in the neurotransmitter system mediating relaxation of the rat anococcygeus muscle. Clin Exp Pharmacol Physiol. 1989 Dec;16(12):933–938. doi: 10.1111/j.1440-1681.1989.tb02404.x. [DOI] [PubMed] [Google Scholar]
  17. Low J. A. Urethral behavior during the involuntary detrusor contraction. Am J Obstet Gynecol. 1977 May 1;128(1):32–42. doi: 10.1016/0002-9378(77)90292-7. [DOI] [PubMed] [Google Scholar]
  18. Moncada S. The 1991 Ulf von Euler Lecture. The L-arginine: nitric oxide pathway. Acta Physiol Scand. 1992 Jul;145(3):201–227. doi: 10.1111/j.1748-1716.1992.tb09359.x. [DOI] [PubMed] [Google Scholar]
  19. Moore P. K., Oluyomi A. O., Babbedge R. C., Wallace P., Hart S. L. L-NG-nitro arginine methyl ester exhibits antinociceptive activity in the mouse. Br J Pharmacol. 1991 Jan;102(1):198–202. doi: 10.1111/j.1476-5381.1991.tb12153.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  20. Palmer R. M., Ashton D. S., Moncada S. Vascular endothelial cells synthesize nitric oxide from L-arginine. Nature. 1988 Jun 16;333(6174):664–666. doi: 10.1038/333664a0. [DOI] [PubMed] [Google Scholar]
  21. Palmer R. M., Ferrige A. G., Moncada S. Nitric oxide release accounts for the biological activity of endothelium-derived relaxing factor. Nature. 1987 Jun 11;327(6122):524–526. doi: 10.1038/327524a0. [DOI] [PubMed] [Google Scholar]
  22. Rajfer J., Aronson W. J., Bush P. A., Dorey F. J., Ignarro L. J. Nitric oxide as a mediator of relaxation of the corpus cavernosum in response to nonadrenergic, noncholinergic neurotransmission. N Engl J Med. 1992 Jan 9;326(2):90–94. doi: 10.1056/NEJM199201093260203. [DOI] [PubMed] [Google Scholar]
  23. SCOTT F. B., QUESADA E. M., CARDUS D. STUDIES ON THE DYNAMICS OF MICTURITION: OBSERVATIONS ON HEALTHY MEN. J Urol. 1964 Nov;92:455–463. doi: 10.1016/S0022-5347(17)63987-9. [DOI] [PubMed] [Google Scholar]
  24. Schmidt H. H., Gagne G. D., Nakane M., Pollock J. S., Miller M. F., Murad F. Mapping of neural nitric oxide synthase in the rat suggests frequent co-localization with NADPH diaphorase but not with soluble guanylyl cyclase, and novel paraneural functions for nitrinergic signal transduction. J Histochem Cytochem. 1992 Oct;40(10):1439–1456. doi: 10.1177/40.10.1382087. [DOI] [PubMed] [Google Scholar]
  25. THOMAS E., PEARSE A. G. THE SOLITARY ACTIVE CELLS. HISTOCHEMICAL DEMONSTRATION OF DAMAGE-RESISTANT NERVE CELLS WITH A TPN-DIAPHORASE REACTION. Acta Neuropathol. 1964 Jan 2;3:238–249. doi: 10.1007/BF00684399. [DOI] [PubMed] [Google Scholar]
  26. Tanagho E. A., Miller E. R. Initiation of voiding. Br J Urol. 1970 Apr;42(2):175–183. doi: 10.1111/j.1464-410x.1970.tb10019.x. [DOI] [PubMed] [Google Scholar]
  27. Thüroff J. W., Casper F., Heidler H. Pelvic floor stress response: reflex contraction with pressure transmission to the urethra. Urol Int. 1987;42(3):185–189. doi: 10.1159/000281892. [DOI] [PubMed] [Google Scholar]
  28. Tøttrup A., Svane D., Forman A. Nitric oxide mediating NANC inhibition in opossum lower esophageal sphincter. Am J Physiol. 1991 Mar;260(3 Pt 1):G385–G389. doi: 10.1152/ajpgi.1991.260.3.G385. [DOI] [PubMed] [Google Scholar]

Articles from British Journal of Pharmacology are provided here courtesy of The British Pharmacological Society

RESOURCES