PULMONARY ACTIONS OF ANANDAMIDE, AN ENDOGENOUS CANNABINOID RECEPTOR AGONIST, IN GUINEA-PIGS

Anandamide (arachidonylethanolamide), 5,8,11,14-eicosatetraenamide, (N -2-hydroxyethyl), was tested for bronchodilator and anti-inflammatory activities. Conscious guinea pigs were given cumulative i.v, doses of anandamide (1.0, 3.0, and 10.0 mg/kg) to assess its effect on dynamic compliance (C-dyn), total pulmonary resistance (R-L), tidal volume (V- T) and breathing frequency (f). Other guinea pigs were exposed to an a erosol of A23187 (6S-[6 alpha(2S ,3S *),8 beta(R *),9 beta,11 iro[5.5 ]undec-2-yl]methyl]-4-benzoxazolecarboxylic acid) until C-dyn decrease d by 50% (similar to 5 min) and at 20 min, cumulative i.v, doses of an andamide (1.0, 3.0, and 10.0 mg/kg) were administered and reversal of C-dyn examined. After the final dose of anandamide, the animals were k illed and excised lung gas volumes (ELGV), i.e., pulmonary gas trappin g, measured. Other animals were treated i.v. with anandamide (10.0 mg/ kg), exposed to an aerosol of A23187 until labored breathing began, an d then killed 1 h later. Anandamide did not significantly affect C-dyn , R-L, V-T and f. ELGV values of anandamide-treated guinea pigs were n ot different from those of vehicle-treated animals. Anandamide failed to reverse A23187-induced decreases in C-dyn and to reduce A23187-asso ciated ELGV increases. Also, it did not prevent the prolonged airway o bstruction caused by A23187. Histological evaluation revealed that ana ndamide significantly reduced A23187-related airway epithelial injury and pulmonary leukocytosis. However, it did not prevent A23187-induced peribronchiolar granulocytic accumulation. Our results suggest that i n vivo anandamide has minimal direct airway smooth muscle-related acti ons, however it may possess modest anti-inflammatory properties. (C) 1 998 Elsevier Science B.V. All rights reserved.