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Am J Physiol Gastrointest Liver Physiol 280: G14-G20, 2001;
0193-1857/01 $5.00
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Vol. 280, Issue 1, G14-G20, January 2001

Systemic and portal hemodynamic effects of anandamide

Nelson Garcia Jr.1, Zoltán Járai2, Faridoddin Mirshahi1, George Kunos2, and Arun J. Sanyal

1 Divisions of Gastroenterology and Hepatology, Department of Internal Medicine, and 2 Department of Pharmacology, Virginia Commonwealth University- Medical College of Virginia, Richmond, Virginia 23298-0711

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, Nomega -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 CB1 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.

portal vein flow; portal vein pressure; cannabinoids; SR-141716A; portal hypertension; blood pressure; splanchnic blood flow; cirrhosis


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