Pharmacological evidence for anandamide amidase in human cardiac and vascular tissues.
The present report demonstrates the presence of antianandamide and anticannabinoid receptor 1 immunopositive material on the saphenous vascular endothelium. The endogenous cannabinoid, anandamide, in a dose-dependent manner stimulated the release of nitric oxide (NO) from saphenous vein, internal thoracic artery and right atrium tissue segments in vitro. This process can be antagonized by the nitric oxide synthase (NOS) 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 I antagonist SR 141716A (2.9+/-1.0 nM NO; P<0.01). Furthermore, in the presence of varying concentrations of methylarachidonylfluorophosphonate, an anandamide amidase inhibitor, 10(-8) M anandamide stimulates a higher peak level of NO that remains elevated for a longer period of time (P<0.05) compared to anandamide alone, demonstrating the presence of anandamide amidase in human vascular tissues. Morphine, as anandamide, can stimulate the release of NO from right atria. This process can be inhibited by the opiate receptor antagonist naloxone and the NOS inhibitor L-NAME. As expected SR 141716A (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 data demonstrate that cannabinoid signalling is involved with the regulation of the microvascular environment.
Department of Surgery, Health Sciences Center, State University of New York at Stony Brook, 11794, USA.
T V
TV
Bilfinger
M
M
Salzet
C
C
Fimiani
D G
DG
Deutsch
G
G
Tramu
G B
GB
Stefano
D000581:Amidohydrolases / Q000037:antagonists & inhibitors / Q000378:metabolism*; D002186:Cannabinoids / Q000378:metabolism; D004730:Endothelium, Vascular / Q000378:metabolism*; D006325:Heart Atria / Q000378:metabolism; D006801:Humans; D009206:Myocardium / Q000378:metabolism*; D009569:Nitric Oxide / Q000378:metabolism; D012501:Saphenous Vein / Q000378:metabolism; D013895:Thoracic Arteries / Q000378:metabolism
D002186:Cannabinoids; D009569:Nitric Oxide; D000581:Amidohydrolases; C087226:arachidonoylethanolamide synthase