Systemic and portal hemodynamic effects of anandamide.
The endogenous cannabinoid anandamide causes hypotension and mesenteric arteriolar dilation. A detailed analysis of its effects on systemic and portal venous hemodynamics had not yet been performed. We assessed the effects of anandamide (0.4-10 mg/kg) on systemic and portal hemodynamics with and without prior treatment with various antagonists. The specific antagonists used included SR-141716A, N(omega)-nitro-L-arginine methyl ester, indomethacin, and nordihydroguaiaretic acid. Anandamide produced a dose-dependent decrease in mean arterial pressure due to a drop in systemic vascular resistance (SVR) that was accompanied by a compensatory rise in cardiac output. Anandamide also elicited an increase in both portal venous flow and pressure, along with a decline in mesenteric vascular resistance (MVR). Pretreatment with 3 mg/kg SR-141716A, a CB(1) antagonist, prevented the decline of SVR and MVR from the lower dose of anandamide. Antagonism of nitric oxide synthetase, cyclooxygenase, or 5-lipoxygenase did not prevent the systemic nor the portal hemodynamic effects of anandamide. Furthermore, the use of R-methanandamide, a stable analog of anandamide, produced similar hemodynamic effects on the mesenteric vasculature, thereby implying that the effects of anandamide are not related to its breakdown products. Anandamide produced profound, dose-dependent alterations in both the systemic and portal circulations that could be at least partially blocked by pretreatment with SR-141716A.
Garcia
N
N
Divisions of Gastroenterology and Hepatology, Department of Internal Medicine, Virginia Commonwealth University- Medical College of Virginia, Richmond, Virginia 23298-0711, USA.
Járai
Z
Z
Mirshahi
F
F
Kunos
G
G
Sanyal
A J
AJ
D000818:Animals; D001095:Arachidonic Acids / Q000494:pharmacology*; D001794:Blood Pressure / Q000187:drug effects* / Q000502:physiology; D002121:Calcium Channel Blockers / Q000494:pharmacology*; D002186:Cannabinoids / Q000037:antagonists & inhibitors; D002302:Cardiac Output / Q000187:drug effects / Q000502:physiology; D016861:Cyclooxygenase Inhibitors / Q000494:pharmacology; D063388:Endocannabinoids; D004791:Enzyme Inhibitors / Q000494:pharmacology; D006339:Heart Rate / Q000187:drug effects / Q000502:physiology; D006975:Hypertension, Portal / Q000188:drug therapy / Q000503:physiopathology; D007213:Indomethacin / Q000494:pharmacology; D008102:Liver Circulation / Q000187:drug effects* / Q000502:physiology; D008297:Male; D009637:Masoprocol / Q000494:pharmacology; D008638:Mesenteric Arteries / Q000187:drug effects / Q000502:physiology; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology; D010880:Piperidines / Q000494:pharmacology; D053284:Polyunsaturated Alkamides; D011169:Portal Vein / Q000187:drug effects / Q000502:physiology; D011720:Pyrazoles / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D000077285:Rimonabant; D013152:Splanchnic Circulation / Q000187:drug effects / Q000502:physiology
D001095:Arachidonic Acids; D002121:Calcium Channel Blockers; D002186:Cannabinoids; D016861:Cyclooxygenase Inhibitors; D063388:Endocannabinoids; D004791:Enzyme Inhibitors; D010880:Piperidines; D053284:Polyunsaturated Alkamides; D011720:Pyrazoles; D009637:Masoprocol; D000077285:Rimonabant; C078814:anandamide; D019331:NG-Nitroarginine Methyl Ester; D007213:Indomethacin