Anandamide induces cardiovascular and respiratory reflexes via vasosensorynerves in the anaesthetized rat

1 We tested the hypothesis that sensory nerves innervating blood vessels pl ay a role in the local and systemic regulation of the cardiovascular and re spiratory (CVR) systems. We measured CVR reflexes evoked by administration of anandamide (86 - 863 nmoles) and capsaicin (0.3 - 10 nmoles) into the hi ndlimb vasculature of anaesthetized rats. 2 Anandamide and capsaicin each caused a rapid dose-dependent reflex fall i n blood pressure and an increase in ventilation when injected intra-arteria lly into the hindlimb. 3 Action of both agonists at the vanilloid receptor (VR1) on perivascular s ensory nerves was investigated using capsazepine (1 mg kg(-1) i.a.) a compe titive VR1 antagonist, ruthenium red (1 mg kg(-1) i.a.), a non-competitive antagonist at VR1, or a desensitizing dose of capsaicin (200 nmoles i.a.). The cannabinoid receptor antagonist SR141716 (1 mg kg(-1) i.a.) was used to determine agonist activity at the CB, receptor. 4 Capsazepine, ruthenium red, or acute VR1 desensitization by capsaicin-pre treatment, markedly attenuated the reflex CVR responses evoked by anandamid e and capsaicin (P <0.05; paired Student's t-test). Blockade of CB, had no significant effect on the responses to anandamide. 5 Local sectioning of the femoral and sciatic nerves attenuated CVR respons es to anandamide and capsaicin (P <0.05). Vagotomy or carotid sinus section ing had no significant effect on anandamide-or capsaicin-induced responses. 6 These data demonstrate that both the endogenous cannabinoid, anandamide, and the vanilloid, capsaicin, evoke CVR reflexes when injected intra-arteri ally into the rat hindlimb. These responses appear to be mediated reflexly via VR1 located on sensory nerve endings within the hindlimb vasculature.