Endogenous cannabinoids: a new system involved in the homeostasis of arterial pressure in experimental cirrhosis in the rat.
OBJECTIVE
Recent studies have described the existence of endogenous cannabinoids with vasodilator activity because of their interaction with peripheral CB1 receptors, anandamide being the most extensively investigated. The study investigated whether endogenous cannabinoids are involved in the pathogenesis of the cardiovascular disturbances in experimental cirrhosis.


METHODS
Arterial pressure, cardiac output, and total peripheral resistance were measured before and after the administration of a cannabinoid CB1 receptor antagonist to cirrhotic rats with ascites and to control rats. Blood pressure was also assessed in normotensive recipient rats after the intravenous administration of blood cells or isolated monocytes obtained from cirrhotic and control rats. Moreover, the endogenous content of anandamide was measured in circulating monocytes of cirrhotic and control rats by gas chromatography/mass spectrometry.


RESULTS
CB1 receptor blockade did not modify systemic hemodynamics in control rats, but significantly increased arterial pressure and peripheral resistance in cirrhotic animals. Blood cell suspension or monocytes from cirrhotic animals, but not from controls, induced arterial hypotension in recipient rats. Finally, anandamide was solely detected in monocytes of cirrhotic animals.


CONCLUSIONS
Monocytes of cirrhotic rats with ascites are activated to produce anandamide and this substance contributes to arterial hypotension in experimental cirrhosis.
Ros
Josefa
J
Hormonal Laboratory, Hospital Clínic Universitari, Barcelona, Spain.
Clària
Joan
J
To-Figueras
Jordi
J
Planagumà
Anna
A
Cejudo-Martín
Pilar
P
Fernández-Varo
Guillermo
G
Martín-Ruiz
Raúl
R
Arroyo
Vicente
V
Rivera
Francisca
F
Rodés
Juan
J
Jiménez
Wladmiro
W
D000818:Animals; D001095:Arachidonic Acids / Q000032:analysis; D001794:Blood Pressure / Q000187:drug effects / Q000502:physiology*; D002186:Cannabinoids / Q000378:metabolism*; D063388:Endocannabinoids; D004791:Enzyme Inhibitors / Q000494:pharmacology; D006706:Homeostasis / Q000502:physiology*; D008106:Liver Cirrhosis, Experimental / Q000378:metabolism*; D008297:Male; D009000:Monocytes / Q000737:chemistry / Q000378:metabolism / Q000637:transplantation; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology; D010880:Piperidines / Q000494:pharmacology; D053284:Polyunsaturated Alkamides; D011720:Pyrazoles / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D043882:Receptors, Cannabinoid; D011955:Receptors, Drug / Q000037:antagonists & inhibitors; D000077285:Rimonabant; D014655:Vascular Resistance / Q000187:drug effects / Q000502:physiology
D001095:Arachidonic Acids; D002186:Cannabinoids; D063388:Endocannabinoids; D004791:Enzyme Inhibitors; D010880:Piperidines; D053284:Polyunsaturated Alkamides; D011720:Pyrazoles; D043882:Receptors, Cannabinoid; D011955:Receptors, Drug; D000077285:Rimonabant; C078814:anandamide; D019331:NG-Nitroarginine Methyl Ester