Effects of endocannabinoids in mice lacking fatty acide amide hydrolase

Written by Brassai Attila, Pacher Pál, Bátkai Sándor, Offertáler László, Douglas Osei-Hyiaman, Jie Liu, Judy Harvey-White, Bán Erika-Gyöngyi, Kovács Ágnes, Járai Zoltán, Benjamin F. Cravatt, Kunos György

The endocannabinoid anandamide exerts neurobehavioral, cardiovascular and immune-regulatory effects through cannabinoid receptors (CB). FAAH is an enzyme responsible for the in vivo degradation of anandamide. Recent experimental studies have suggested that targeting the endocannabinergic system by FAAH inhibitors is a promising approach for the treatment of anxiety, inflammation and hypertension. In this study we compared the effects of anandamid and HU210 and also the Western blot and the baroreflex sensitivity of FAAH knockout (FAAH-/-) mice and their wild-type (FAAH+/+) littermates. Baseline cardiovascular parameters were similar in FAAH-/- and FAAH+/+ mice. FAAH-/- mice displayed increased sensitivity to anandamideinduced, CB1-mediated hypotension and decreased cardiac contractility compared to FAAH+/+ littermates. Our results indicate that mice lacking FAAH have a normal hemodynamic profile, but they have a higher anandamid concentration in their myocardium.

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