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Nicotine in High Concentration Causes Contraction of Isolated Strips of Rabbit Corpus Cavernosum

  • Nguyen, Hoai Bac (Advanced Urogenital Disease Research Center, Research Institute for Translational System Biomics, Department of Urology, Chung-Ang University Hospital) ;
  • Lee, Shin Young (Department of Urology, Seoul Medical Center) ;
  • Park, Soo Hyun (Department of Physiology, College of Medicine, Chung-Ang University) ;
  • Han, Jun Hyun (Department of Urology, Hallym University Dongtan Sacred Heart Hospital) ;
  • Lee, Moo Yeol (Department of Physiology, College of Medicine, Chung-Ang University) ;
  • Myung, Soon Chul (Advanced Urogenital Disease Research Center, Research Institute for Translational System Biomics, Department of Urology, Chung-Ang University Hospital)
  • Received : 2015.01.05
  • Accepted : 2015.04.08
  • Published : 2015.05.01

Abstract

It is well known that cigarette smoke can cause erectile dysfunction by affecting the penile vascular system. However, the exact effects of nicotine on the corpus cavernosum remains poorly understood. Nicotine has been reported to cause relaxation of the corpus cavernosum; it has also been reported to cause both contraction and relaxation. Therefore, high concentrations of nicotine were studied in strips from the rabbit corpus cavernosum to better understand its effects. The proximal penile corpus cavernosal strips from male rabbits weighing approximately 4 kg were used in organ bath studies. Nicotine in high concentrations ($10^{-5}{\sim}10^{-4}M$) produced dose-dependent contractions of the corpus cavernosal strips. The incubation with $10^{-5}M$ hexamethonium (nicotinic receptor antagonist) significantly inhibited the magnitude of the nicotine associated contractions. The nicotine-induced contractions were not only significantly inhibited by pretreatment with $10^{-5}M$ indomethacin (nonspecific cyclooxygenase inhibitor) and with $10^{-6}M$ NS-398 (selective cyclooxygenase inhibitor), but also with $10^{-6}M$ Y-27632 (Rho kinase inhibitor). Ozagrel (thromboxane $A_2$ synthase inhibitor) and SQ-29548 (highly selective TP receptor antagonist) pretreatments significantly reduced the nicotine-induced contractile amplitude of the strips. High concentrations of nicotine caused contraction of isolated rabbit corpus cavernosal strips. This contraction appeared to be mediated by activation of nicotinic receptors. Rho-kinase and cyclooxygenase pathways, especially cyclooxygenase-2 and thromboxane $A_2$, might play a pivotal role in the mechanism associated with nicotine-induced contraction of the rabbit corpus cavernosum.

Keywords

References

  1. McVary KT, Carrier S, Wessells H; Subcommittee on Smoking and Erectile Dysfunction Socioeconomic Committee, Sexual Medicine Society of North America. Smoking and erectile dysfunction: evidence based analysis. J Urol. 2001;166:1624-1632. https://doi.org/10.1016/S0022-5347(05)65641-8
  2. 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. N Engl J Med 1989;320:1025-1030. https://doi.org/10.1056/NEJM198904203201601
  3. Henningfield JE, Fant RV, Buchhalter AR, Stitzer ML. Pharmacotherapy for nicotine dependence. CA Cancer J Clin. 2005; 55:281-299; quiz 322-323, 325. https://doi.org/10.3322/canjclin.55.5.281
  4. Hukkanen J, Jacob P 3rd, Benowitz NL. Metabolism and disposition kinetics of nicotine. Pharmacol Rev. 2005;57:79-115. https://doi.org/10.1124/pr.57.1.3
  5. Benowitz NL. Pharmacology of nicotine: addiction and therapeutics. Annu Rev Pharmacol Toxicol. 1996;36:597-613. https://doi.org/10.1146/annurev.pa.36.040196.003121
  6. Zainalabidin S, Budin SB, Ramalingam A, Lim YC. Aortic remodelling in chronic nicotine-administered rat. Korean J Physiol Pharmacol. 2014;18:411-418. https://doi.org/10.4196/kjpp.2014.18.5.411
  7. Pickering TG, Schwartz JE, James GD. Ambulatory blood pressure monitoring for evaluating the relationships between lifestyle, hypertension and cardiovascular risk. Clin Exp Pharmacol Physiol. 1995;22:226-231. https://doi.org/10.1111/j.1440-1681.1995.tb01986.x
  8. Gunby P. Surgeon General emphasizes nicotine addiction in annual report on tobacco use, consequences. JAMA. 1988;259:2811. https://doi.org/10.1001/jama.1988.03720190003002
  9. Hanna ST. Nicotine effect on cardiovascular system and ion channels. J Cardiovasc Pharmacol. 2006;47:348-358.
  10. Hayashida H, Okamura T, Tomoyoshi T, Toda N. Neurogenic nitric oxide mediates relaxation of canine corpus cavernosum. J Urol. 1996;155:1122-1127. https://doi.org/10.1016/S0022-5347(01)66404-8
  11. Bagcivan I, Gokce G, Yildirim S, Sarioglu Y. Investigation of the mechanism of nicotine induced relaxation in rabbit corpus cavernosum in vitro. Urol Res. 2004;32:209-212.
  12. Klinge E, Alaranta S, Sjostrand NO. Pharmacological analysis of nicotinic relaxation of bovine retractor penis muscle. J Pharmacol Exp Ther. 1988;245:280-286.
  13. Bozkurt NB, Vural IM, Sarioglu Y, Pekiner C. Nicotine potentiates the nitrergic relaxation responses of rabbit corpus cavernosum tissue via nicotinic acetylcholine receptors. Eur J Pharmacol. 2007;558:172-178. https://doi.org/10.1016/j.ejphar.2006.11.053
  14. 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. https://doi.org/10.1254/jjp.72.231
  15. Ozturk Fincan GS, Vural IM, Ercan ZS, Sarioglu Y. Enhancement effects of nicotine on neurogenic relaxation responses in the corpus cavernosum in rabbits: the role of nicotinic acetylcholine receptor subtypes. Eur J Pharmacol. 2010;627:281-284. https://doi.org/10.1016/j.ejphar.2009.10.042
  16. Albuquerque EX, Pereira EF, Alkondon M, Rogers SW. Mammalian nicotinic acetylcholine receptors: from structure to function. Physiol Rev. 2009;89:73-120. https://doi.org/10.1152/physrev.00015.2008
  17. Webb RC. Smooth muscle contraction and relaxation. Adv Physiol Educ. 2003;27:201-206. https://doi.org/10.1152/advances.2003.27.4.201
  18. Rees RW, Ralph DJ, Royle M, Moncada S, Cellek S. Y-27632, an inhibitor of Rho-kinase, antagonizes noradrenergic contractions in the rabbit and human penile corpus cavernosum. Br J Pharmacol. 2001;133:455-458. https://doi.org/10.1038/sj.bjp.0704124
  19. Wingard CJ, Husain S, Williams J, James S. RhoA-Rho kinase mediates synergistic ET-1 and phenylephrine contraction of rat corpus cavernosum. Am J Physiol Regul Integr Comp Physiol. 2003;285:R1145-1152. https://doi.org/10.1152/ajpregu.00329.2003
  20. Needleman P, Moncada S, Bunting S, Vane JR, Hamberg M, Samuelsson B. Identification of an enzyme in platelet microsomes which generates thromboxane A2 from prostaglandin endoperoxides. Nature. 1976;261:558-560. https://doi.org/10.1038/261558a0
  21. Claria J. Cyclooxygenase-2 biology. Curr Pharm Des. 2003;9: 2177-2190. https://doi.org/10.2174/1381612033454054
  22. Crofford LJ, Lipsky PE, Brooks P, Abramson SB, Simon LS, van de Putte LB. Basic biology and clinical application of specific cyclooxygenase-2 inhibitors. Arthritis Rheum. 2000;43: 4-13. https://doi.org/10.1002/1529-0131(200001)43:1<4::AID-ANR2>3.0.CO;2-V
  23. Ji X, Nishihashi T, Trandafir CC, Wang A, Shimizu Y, Kurahashi K. Pharmacological nature of nicotine-induced contraction in the rat basilar artery: involvement of arachidonic acid metabolites. Eur J Pharmacol. 2007;577:109-114. https://doi.org/10.1016/j.ejphar.2007.08.011
  24. Daley JT, Brown ML, Watkins T, Traish AM, Huang YH, Moreland RB, De Tejada IS. Prostanoid production in rabbit corpus cavernosum: I. regulation by oxygen tension. J Urol. 1996;155:1482-1487. https://doi.org/10.1016/S0022-5347(01)66311-0
  25. Daley JT, Watkins MT, Brown ML, Martinez V, Cuevas P, Saenz de Tejada I. Prostanoid production in rabbit corpus cavernosum. II. Inhibition by oxidative stress. J Urol. 1996;156: 1169-1173. https://doi.org/10.1016/S0022-5347(01)65744-6
  26. Moreland RB, Albadawi H, Bratton C, Patton G, Goldstein I, Traish A, Watkins MT. O2-dependent prostanoid synthesis activates functional PGE receptors on corpus cavernosum smooth muscle. Am J Physiol Heart Circ Physiol. 2001;281:H552-558. https://doi.org/10.1152/ajpheart.2001.281.2.H552
  27. Angulo J, Cuevas P, La Fuente JM, Pomerol JM, Ruiz-Castane E, Puigvert A, Gabancho S, Fernandez A, Ney P, Saenz De Tejada I. Regulation of human penile smooth muscle tone by prostanoid receptors. Br J Pharmacol. 2002;136:23-30. https://doi.org/10.1038/sj.bjp.0704675
  28. Hedlund H, Andersson KE. Contraction and relaxation induced by some prostanoids in isolated human penile erectile tissue and cavernous artery. J Urol. 1985;134:1245-1250. https://doi.org/10.1016/S0022-5347(17)47704-4

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  1. Involvement of Arachidonic Acid Metabolites Pathway and Nicotinic Acetylcholine Receptors (nAChRs) on Nicotine-induced Contractions (or Relaxations) in the Basilar Artery vol.13, pp.1, 2017, https://doi.org/10.3923/ijp.2017.1.10