PHARMACOLOGICAL EVIDENCE FOR ANANDAMIDE AMIDASE IN HUMAN CARDIAC AND VASCULAR TISSUES

The present report demonstrates the presence of antianandamide and ant icannabinoid receptor 1 immunopositive material on the saphenous vascu lar endothelium. The endogenous cannabinoid, anandamide, in a dose-dep endent manner stimulated the release of nitric oxide (NO) from sapheno us vein, internal thoracic artery and right atrium tissue segments in vitro. This process can be antagonized by the nitric oxide synthase (N OS) inhibitor, N-omega-nitro-L-arginine methyl ester (L-NAME) (10(-4) M; 3.4 +/- 0.9 nM NO; P<0.01 compared to anandamide alone), as well as by the cannabinoid receptor 1 antagonist SR 141716A (2.9 +/- 1.0 nM N O; P<0,01). Furthermore, in the presence of varying concentrations of methylarachidonylfluorophosphonate, an anandamide amidase inhibitor, 1 0(-8) M anandamide stimulates a higher peak level of NO that remains e levated for a longer period of time (P<0.05) compared to anandamide al one, demonstrating the presence of anandamide amidase in human vascula r tissues. Morphine, as anandamide, can stimulate the release of NO fr om right atria. This process can be inhibited by the opiate receptor a ntagonist naloxone and the NOS inhibitor L-NAME. As expected SR 141716 A (10(-6) M; 26 + 3.8 NO nM in the presence of 10(-7) M morphine) did not antagonize morphine's ability to release NO. Taken together, the d ata demonstrate that cannabinoid signalling is involved with the regul ation of the microvascular environment. (C) 1998 Elsevier Science Irel and Ltd.