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


METHODS
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.


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
Cirrhosis potentiates the neurogenic relaxation of rat corpus cavernosum probably via the NO pathway and involving cannabinoid CB(1) and vanilloid VR(1) receptors.
Ghasemi
M
M
Department of Pharmacology, School of Medicine, Medical Sciences/University of Tehran, Tehran, Iran.
Sadeghipour
H
H
Shafaroodi
H
H
Nezami
B G
BG
Gholipour
T
T
Hajrasouliha
A R
AR
Tavakoli
S
S
Nobakht
M
M
Moore
K P
KP
Mani
A R
AR
Dehpour
A R
AR
D000818:Animals; D001095:Arachidonic Acids / Q000494:pharmacology; D001120:Arginine / Q000031:analogs & derivatives / Q000494:pharmacology; D015153:Blotting, Western; D063385:Cannabinoid Receptor Modulators / Q000502:physiology*; D002186:Cannabinoids / Q000494:pharmacology; D004558:Electric Stimulation; D063388:Endocannabinoids; D004791:Enzyme Inhibitors / Q000494:pharmacology; D066298:In Vitro Techniques; D008105:Liver Cirrhosis, Biliary / Q000503:physiopathology*; D008297:Male; D009126:Muscle Relaxation / Q000187:drug effects / Q000502:physiology; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology; D009569:Nitric Oxide / Q000502:physiology*; D020030:Nitric Oxide Donors / Q000494:pharmacology; D052248:Nitric Oxide Synthase Type I / Q000037:antagonists & inhibitors / Q000378:metabolism; D009599:Nitroprusside / Q000494:pharmacology; D010413:Penis / Q000294:innervation / Q000503:physiopathology*; D010656:Phenylephrine / Q000494:pharmacology; D053284:Polyunsaturated Alkamides / Q000494:pharmacology; D051381:Rats; D015398:Signal Transduction / Q000502:physiology*; D050916:TRPV Cation Channels / Q000037:antagonists & inhibitors; D014662:Vasoconstrictor Agents / Q000494:pharmacology
D001095:Arachidonic Acids; D063385:Cannabinoid Receptor Modulators; D002186:Cannabinoids; D063388:Endocannabinoids; D004791:Enzyme Inhibitors; C109599:N(omega)-propylarginine; D020030:Nitric Oxide Donors; D053284:Polyunsaturated Alkamides; D050916:TRPV Cation Channels; D014662:Vasoconstrictor Agents; D009599:Nitroprusside; D010656:Phenylephrine; D009569:Nitric Oxide; D001120:Arginine; D052248:Nitric Oxide Synthase Type I; C078814:anandamide; D019331:NG-Nitroarginine Methyl Ester