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 microM 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 (TRPV1) antagonist
capsazepine inhibited this effect. The TRPV1 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 TRPV1 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 TRPV1 on primary sensory nerves, but do not support a role for
anandamide as a circulating vasoactive
hormone in the human forearm vascular bed.