Role of the nitric oxide pathway and the endocannabinoid system in neurogenic relaxation of corpus cavernosum from biliary cirrhotic rats

M. Ghasemi, H. Sadeghipour, H. Shafaroodi, B. G. Nezami, T. Gholipour, Amir R. Hajrasouliha, S. Tavakoli, M. Nobakht, K. P. Moore, A. R. Mani, A. R. Dehpour

Research output: Contribution to journalArticle

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Abstract

Background and purpose: Relaxation of corpus cavernosum, which is mediated by nitric oxide (NO) released from non-adrenergic non-cholinergic (NANC) neurotransmission, is critical for inducing penile erection and can be affected by many pathophysiological conditions. However, the peripheral effect of liver cirrhosis on erectile function is as yet unknown. The aim of the present study was to investigate the effect of biliary cirrhosis on NANC-mediated relaxation of rat corpus cavernosum and the possible roles of endocannabinoid and nitric oxide systems in this model. Experimental approach: Cirrhosis was induced by bile duct ligation. Controls underwent sham operation. Four weeks later, strips of corpus cavernosum were mounted in a standard organ bath and NANC-mediated relaxations were obtained by applying electrical field stimulation. Key results: The NANC-mediated relaxation was enhanced in corporal strips from cirrhotic animals. Anandamide potentiated the relaxations in both groups. Either AM251 (CB 1 antagonist) or capsazepine (vanilloid VR 1 antagonist), but not AM630 (CB 2 antagonist), prevented the enhanced relaxations of cirrhotic strips. Either the non-selective NOS inhibitor L-NAME or the selective neuronal NOS inhibitor L-NPA inhibited relaxations in both groups, but cirrhotic groups were more resistant to the inhibitory effects of these agents. Relaxations to sodium nitroprusside (NO donor) were similar in tissues from the two groups. Conclusions and implications: Cirrhosis potentiates the neurogenic relaxation of rat corpus cavernosum probably via the NO pathway and involving cannabinoid CB 1 and vanilloid VR 1 receptors.

Original languageEnglish (US)
Pages (from-to)591-601
Number of pages11
JournalBritish Journal of Pharmacology
Volume151
Issue number5
DOIs
StatePublished - Jul 14 2007
Externally publishedYes

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Endocannabinoids
Nitric Oxide
Fibrosis
Penile Erection
Nitric Oxide Donors
Biliary Liver Cirrhosis
Cannabinoids
NG-Nitroarginine Methyl Ester
Nitroprusside
Bile Ducts
Baths
Synaptic Transmission
Liver Cirrhosis
Electric Stimulation
Ligation

Keywords

  • Cannabinoids
  • Cirrhosis
  • Corpus cavernosum
  • Erection
  • NANC (non-adrenergic non-cholinergic) relaxation
  • Nitric oxide (NO)
  • Rats

ASJC Scopus subject areas

  • Pharmacology

Cite this

Role of the nitric oxide pathway and the endocannabinoid system in neurogenic relaxation of corpus cavernosum from biliary cirrhotic rats. / Ghasemi, M.; Sadeghipour, H.; Shafaroodi, H.; Nezami, B. G.; Gholipour, T.; Hajrasouliha, Amir R.; Tavakoli, S.; Nobakht, M.; Moore, K. P.; Mani, A. R.; Dehpour, A. R.

In: British Journal of Pharmacology, Vol. 151, No. 5, 14.07.2007, p. 591-601.

Research output: Contribution to journalArticle

Ghasemi, M, Sadeghipour, H, Shafaroodi, H, Nezami, BG, Gholipour, T, Hajrasouliha, AR, Tavakoli, S, Nobakht, M, Moore, KP, Mani, AR & Dehpour, AR 2007, 'Role of the nitric oxide pathway and the endocannabinoid system in neurogenic relaxation of corpus cavernosum from biliary cirrhotic rats', British Journal of Pharmacology, vol. 151, no. 5, pp. 591-601. https://doi.org/10.1038/sj.bjp.0707279
Ghasemi, M. ; Sadeghipour, H. ; Shafaroodi, H. ; Nezami, B. G. ; Gholipour, T. ; Hajrasouliha, Amir R. ; Tavakoli, S. ; Nobakht, M. ; Moore, K. P. ; Mani, A. R. ; Dehpour, A. R. / Role of the nitric oxide pathway and the endocannabinoid system in neurogenic relaxation of corpus cavernosum from biliary cirrhotic rats. In: British Journal of Pharmacology. 2007 ; Vol. 151, No. 5. pp. 591-601.
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abstract = "Background and purpose: Relaxation of corpus cavernosum, which is mediated by nitric oxide (NO) released from non-adrenergic non-cholinergic (NANC) neurotransmission, is critical for inducing penile erection and can be affected by many pathophysiological conditions. However, the peripheral effect of liver cirrhosis on erectile function is as yet unknown. The aim of the present study was to investigate the effect of biliary cirrhosis on NANC-mediated relaxation of rat corpus cavernosum and the possible roles of endocannabinoid and nitric oxide systems in this model. Experimental approach: Cirrhosis was induced by bile duct ligation. Controls underwent sham operation. Four weeks later, strips of corpus cavernosum were mounted in a standard organ bath and NANC-mediated relaxations were obtained by applying electrical field stimulation. Key results: The NANC-mediated relaxation was enhanced in corporal strips from cirrhotic animals. Anandamide potentiated the relaxations in both groups. Either AM251 (CB 1 antagonist) or capsazepine (vanilloid VR 1 antagonist), but not AM630 (CB 2 antagonist), prevented the enhanced relaxations of cirrhotic strips. Either the non-selective NOS inhibitor L-NAME or the selective neuronal NOS inhibitor L-NPA inhibited relaxations in both groups, but cirrhotic groups were more resistant to the inhibitory effects of these agents. Relaxations to sodium nitroprusside (NO donor) were similar in tissues from the two groups. Conclusions and implications: Cirrhosis potentiates the neurogenic relaxation of rat corpus cavernosum probably via the NO pathway and involving cannabinoid CB 1 and vanilloid VR 1 receptors.",
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AU - Ghasemi, M.

AU - Sadeghipour, H.

AU - Shafaroodi, H.

AU - Nezami, B. G.

AU - Gholipour, T.

AU - Hajrasouliha, Amir R.

AU - Tavakoli, S.

AU - Nobakht, M.

AU - Moore, K. P.

AU - Mani, A. R.

AU - Dehpour, A. R.

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N2 - Background and purpose: Relaxation of corpus cavernosum, which is mediated by nitric oxide (NO) released from non-adrenergic non-cholinergic (NANC) neurotransmission, is critical for inducing penile erection and can be affected by many pathophysiological conditions. However, the peripheral effect of liver cirrhosis on erectile function is as yet unknown. The aim of the present study was to investigate the effect of biliary cirrhosis on NANC-mediated relaxation of rat corpus cavernosum and the possible roles of endocannabinoid and nitric oxide systems in this model. Experimental approach: Cirrhosis was induced by bile duct ligation. Controls underwent sham operation. Four weeks later, strips of corpus cavernosum were mounted in a standard organ bath and NANC-mediated relaxations were obtained by applying electrical field stimulation. Key results: The NANC-mediated relaxation was enhanced in corporal strips from cirrhotic animals. Anandamide potentiated the relaxations in both groups. Either AM251 (CB 1 antagonist) or capsazepine (vanilloid VR 1 antagonist), but not AM630 (CB 2 antagonist), prevented the enhanced relaxations of cirrhotic strips. Either the non-selective NOS inhibitor L-NAME or the selective neuronal NOS inhibitor L-NPA inhibited relaxations in both groups, but cirrhotic groups were more resistant to the inhibitory effects of these agents. Relaxations to sodium nitroprusside (NO donor) were similar in tissues from the two groups. Conclusions and implications: Cirrhosis potentiates the neurogenic relaxation of rat corpus cavernosum probably via the NO pathway and involving cannabinoid CB 1 and vanilloid VR 1 receptors.

AB - Background and purpose: Relaxation of corpus cavernosum, which is mediated by nitric oxide (NO) released from non-adrenergic non-cholinergic (NANC) neurotransmission, is critical for inducing penile erection and can be affected by many pathophysiological conditions. However, the peripheral effect of liver cirrhosis on erectile function is as yet unknown. The aim of the present study was to investigate the effect of biliary cirrhosis on NANC-mediated relaxation of rat corpus cavernosum and the possible roles of endocannabinoid and nitric oxide systems in this model. Experimental approach: Cirrhosis was induced by bile duct ligation. Controls underwent sham operation. Four weeks later, strips of corpus cavernosum were mounted in a standard organ bath and NANC-mediated relaxations were obtained by applying electrical field stimulation. Key results: The NANC-mediated relaxation was enhanced in corporal strips from cirrhotic animals. Anandamide potentiated the relaxations in both groups. Either AM251 (CB 1 antagonist) or capsazepine (vanilloid VR 1 antagonist), but not AM630 (CB 2 antagonist), prevented the enhanced relaxations of cirrhotic strips. Either the non-selective NOS inhibitor L-NAME or the selective neuronal NOS inhibitor L-NPA inhibited relaxations in both groups, but cirrhotic groups were more resistant to the inhibitory effects of these agents. Relaxations to sodium nitroprusside (NO donor) were similar in tissues from the two groups. Conclusions and implications: Cirrhosis potentiates the neurogenic relaxation of rat corpus cavernosum probably via the NO pathway and involving cannabinoid CB 1 and vanilloid VR 1 receptors.

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