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Investigation of cavernosal smooth muscle dysfunction in low flow priapism using an in vitro model

International Journal of Impotence Research volume 17, pages 10–18 (2005)Cite this article

Abstract

The effects of hypoxia (pO2: 50 mmHg), acidosis (pH: 6.9) or glucopenia (absence of glucose) in vitro on the tone of the rabbit corpus cavernosum were investigated. The recovery of smooth muscle contractility following exposure to these conditions was also assessed. Hypoxia, acidosis or glucopenia alone or in combination showed a sustained reduction in the tone. Reperfusion of tissue strips showed complete recovery of smooth muscle tone for all conditions except when hypoxia and glucopenia were combined or when hypoxia, glucopenia and acidosis were used in combination. Incomplete recovery of tone was associated with a significant reduction in tissue ATP concentrations and an increase in the number of TUNEL (terminal deoxynucleotidyl transferase-mediated dUTP nick-end labelling)-positive nuclei. This indicates that following reversal of hypoxia, acidosis and glucopenia, failure of conventional α-adrenergic agonists to produce tumescence in low flow priapism is associated with irreversible smooth muscle cell dysfunction, which is linked to ATP reduction and smooth muscle cell death.

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References

  1. Broderick GA, Harkaway R . Pharmacologic erection: time-dependent changes in the corporal environment. Int J Impot Res 1994; 6: 9–16.

    CAS  PubMed  Google Scholar 

  2. Rees RW et al. The management of low-flow priapism with the immediate insertion of a penile prosthesis. BJU Int 2002; 90: 893–897.

    Article  CAS  Google Scholar 

  3. Bertram RA, Webster GD, Carson III CC . Priapism: etiology, treatment, and results in series of 35 presentations. Urology 1985; 26: 229–232.

    Article  CAS  Google Scholar 

  4. Broderick GA et al. Anoxia and corporal smooth muscle dysfunction: a model for ischemic priapism. J Urol 1994; 151: 259–262.

    Article  CAS  Google Scholar 

  5. Kim NN et al. Altered contractility of rabbit penile corpus cavernosum smooth muscle by hypoxia. J Urol 1996; 155: 772–778.

    Article  CAS  Google Scholar 

  6. Saenz dT I et al. Acidosis impairs rabbit trabecular smooth muscle contractility. J Urol 1997; 157: 722–726.

    Article  Google Scholar 

  7. Liu SP, Horan P, Levin RM . Digital analysis of the pharmacological effects of in vitro ischemia on rabbit corpus cavernosum. Pharmacology 1998; 56: 216–222.

    Article  CAS  Google Scholar 

  8. Liu SP, Mogavero LJ, Levin RM . Correlation of calcium-activated ATPase activity, lipid peroxidation, and the contractile response of rabbit corporal smooth muscle treated with in vitro ischemia. Gen Pharmacol 1999; 32: 345–349.

    Article  CAS  Google Scholar 

  9. Kim JJ, Moon DG, Koh SK . The role of nitric oxide in vivo feline erection under hypoxia. Int J Impot Res 1998; 10: 145–150.

    Article  CAS  Google Scholar 

  10. Moon DG, Lee DS, Kim JJ . Altered contractile response of penis under hypoxia with metabolic acidosis. Int J Impot Res 1999; 11: 265–271.

    Article  CAS  Google Scholar 

  11. Reiner PB, Laycock AG, Doll CJ . A pharmacological model of ischemia in the hippocampal slice. Neurosci Lett 1990; 119: 175–178.

    Article  CAS  Google Scholar 

  12. Knull HR, Bose D . Reversibility of mechanical and biochemical changes in smooth muscle due to anoxia and substrate depletion. Am J Physiol 1975; 229: 329–333.

    Article  CAS  Google Scholar 

  13. Corbett AD, Lees GM . Depressant effects of hypoxia and hypoglycaemia on neuro-effector transmission of guinea-pig intestine studied in vitro with a pharmacological model. Br J Pharmacol 1997; 120: 107–115.

    Article  CAS  Google Scholar 

  14. Pessina F et al. The effect of anoxia and glucose-free solutions on the contractile response of guinea-pig detrusor strips to intrinsic nerve stimulation and the application of excitatory agonists. J Urol 1997; 157: 2375–2380.

    Article  CAS  Google Scholar 

  15. Cellek S, Moncada S . Nitrergic control of peripheral sympathetic responses in the human corpus cavernosum: a comparison with other species. Proc Natl Acad Sci USA 1997; 94: 8226–8231.

    Article  CAS  Google Scholar 

  16. Bradford MM . A rapid and sensitive method for the quantitation of microgram quantities of protein utilizing the principle of protein-dye binding. Anal Biochem 1976; 72: 248–254.

    Article  CAS  Google Scholar 

  17. Dogan A et al. Micronodular T-cell/histiocyte-rich large B-cell lymphoma of the spleen: histology, immunophenotype, and differential diagnosis. Am J Surg Pathol 2003; 27: 903–911.

    Article  Google Scholar 

  18. Rees DD et al. Dexamethasone prevents the induction by endotoxin of a nitric oxide synthase and the associated effects on vascular tone: an insight into endotoxin shock. Biochem Biophys Res Commun 1990; 173: 541–547.

    Article  CAS  Google Scholar 

  19. Cellek S, Moncada S . Modulation of noradrenergic responses by nitric oxide from inducible nitric oxide synthase. Nitric Oxide 1997; 1: 204–210.

    Article  CAS  Google Scholar 

  20. Soloviev AI, Basilyuk OV . Evidence for decrease in myofilament responsiveness to Ca2+ during hypoxia in spontaneously active vascular smooth muscle in rats. Exp Physiol 1993; 78: 395–402.

    Article  CAS  Google Scholar 

  21. Austin C, Wray S . Extracellular pH signals affect rat vascular tone by rapid transduction into intracellular pH changes. J Physiol 1993; 466: 1–8.

    Article  CAS  Google Scholar 

  22. Stadelmann C, Lassmann H . Detection of apoptosis in tissue sections. Cell Tissue Res 2000; 301: 19–31.

    Article  CAS  Google Scholar 

  23. Carmeliet P et al. Role of HIF-1alpha in hypoxia-mediated apoptosis, cell proliferation and tumour angiogenesis. Nature 1998; 394: 485–490.

    Article  CAS  Google Scholar 

  24. Bruick RK . Oxygen sensing in the hypoxic response pathway: regulation of the hypoxia-inducible transcription factor. Genes Dev 2003; 17: 2614–2623.

    Article  CAS  Google Scholar 

  25. Dong Z et al. Up-regulation of apoptosis inhibitory protein IAP-2 by hypoxia. Hif-1-independent mechanisms. J Biol Chem 2001; 276: 18702–18709.

    Article  CAS  Google Scholar 

  26. El Bahnasawy MS, Dawood A, Farouk A . Low-flow priapism: risk factors for erectile dysfunction. BJU Int 2002; 89: 285–290.

    Article  CAS  Google Scholar 

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Acknowledgements

A Muneer and this work are supported by St Peter's Andrology Research Fund. S Cellek is a fellow of Juvenile Diabetes Research Foundation International. The authors thank Dr V Hollis for help in measuring pO2.

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Authors and Affiliations

  1. The St Peter's Andrology Centre, University College London, London, UK

    A Muneer, P D Kell, D J Ralph & S Minhas

  2. Wolfson Institute for Biomedical Research, University College London, London, UK

    A Muneer & S Cellek

  3. Department of Histopathology, University College London, London, UK

    A Dogan

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  1. A Muneer
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  2. S Cellek
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  3. A Dogan
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  4. P D Kell
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Correspondence to S Minhas.

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Muneer, A., Cellek, S., Dogan, A. et al. Investigation of cavernosal smooth muscle dysfunction in low flow priapism using an in vitro model. Int J Impot Res 17, 10–18 (2005). https://doi.org/10.1038/sj.ijir.3901231

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  • DOI: https://doi.org/10.1038/sj.ijir.3901231

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