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

Ghasemi, M. and Sadeghipour, H. and Shafaroodi, H. and Nezami, B.G. and Gholipour, T. and Hajrasouliha, A.R. and Tavakoli, S. and Nobakht, M. and Moore, K.P. and Mani, A.R. and Dehpour, A.R. (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, 151 (5). pp. 591-601.

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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. © 2007 Nature Publishing Group All rights reserved.

Item Type: Article
Additional Information: cited By 20
Uncontrolled Keywords: 1 (2,4 dichlorophenyl) 5 (4 iodophenyl) 4 methyl n (1 piperidyl) 1h pyrazole 3 carboxamide; 6 iodo 3 (4 methoxybenzoyl) 2 methyl 1 (2 morpholinoethyl)indole; anandamide; arginine derivative; cannabinoid 1 receptor; cannabinoid 2 receptor; cannabinoid receptor antagonist; capsazepine; endocannabinoid; n propyl l arginine; n(g) nitroarginine methyl ester; nitric oxide; nitric oxide synthase inhibitor; nitroprusside sodium; unclassified drug; vanilloid receptor 1, animal experiment; animal model; animal tissue; article; bile duct ligation; biliary cirrhosis; controlled study; corpus cavernosum; drug inhibition; drug potentiation; electrostimulation; male; neurotransmission; nonhuman; priority journal; rat, Animals; Arachidonic Acids; Arginine; Blotting, Western; Cannabinoids; Electric Stimulation; Endocannabinoids; Enzyme Inhibitors; Liver Cirrhosis, Biliary; Male; Muscle Relaxation; NG-Nitroarginine Methyl Ester; Nitric Oxide; Nitric Oxide Donors; Nitric Oxide Synthase Type I; Nitroprusside; Penis; Phenylephrine; Polyunsaturated Alkamides; Rats; Signal Transduction; TRPV Cation Channels; Vasoconstrictor Agents
Subjects: QV Pharmacology
Divisions: School of Rehabilitation Sciences
Depositing User: parto mrs bakhtminoo
Date Deposited: 26 Feb 2019 10:31
Last Modified: 26 Feb 2019 10:31

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