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Vascular effects of anandamide and N ‐acylvanillylamines in the human forearm and skin microcirculation
Author(s) -
Movahed Pouya,
Evilevitch Vladimir,
Andersson Tomas L G,
Jönsson Bo A G,
Wollmer Per,
Zygmunt Peter M,
Högestätt Edward D
Publication year - 2005
Publication title -
british journal of pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.432
H-Index - 211
eISSN - 1476-5381
pISSN - 0007-1188
DOI - 10.1038/sj.bjp.0706313
Subject(s) - anandamide , capsazepine , trpv1 , vasodilation , medicine , endocannabinoid system , microcirculation , cannabinoid receptor , anesthesia , chemistry , microneurography , endocrinology , heart rate , transient receptor potential channel , receptor , antagonist , blood pressure , baroreflex
The endocannabinoid anandamide is an emerging potential signalling molecule in the cardiovascular system. Anandamide causes vasodilatation, bradycardia and hypotension in animals and has been implicated in the pathophysiology of endotoxic, haemorrhagic and cardiogenic shock, but its vascular effects have not been studied in man. Human forearm blood flow and skin microcirculatory flow were recorded using venous occlusion plethysmography and laser‐Doppler perfusion imaging (LDPI), respectively. Each test drug was infused into the brachial artery or applied topically on the skin followed by a standardized pin‐prick to disrupt the epidermal barrier. Anandamide failed to affect forearm blood flow when administered intra‐arterially at infusion rates of 0.3–300 nmol min −1 . The highest infusion rate led to an anandamide concentration of approximately 1 μ M in venous blood as measured by mass spectrometry. Dermal application of anandamide significantly increased skin microcirculatory flow and coapplication of the transient receptor potential vanilloid 1 (TRPV 1 ) antagonist capsazepine inhibited this effect. The TRPV 1 agonists capsaicin, olvanil and arvanil all induced concentration‐dependent increases in skin blood flow and burning pain when administered dermally. Coapplication of capsazepine inhibited blood flow and pain responses to all three TRPV 1 agonists. This study shows that locally applied anandamide is a vasodilator in the human skin microcirculation. The results are consistent with this lipid being an activator of TRPV 1 on primary sensory nerves, but do not support a role for anandamide as a circulating vasoactive hormone in the human forearm vascular bed.British Journal of Pharmacology (2005) 146 , 171–179. doi: 10.1038/sj.bjp.0706313