Anandamide induces cardiovascular and respiratory reflexesviavasosensory nerves in the anaesthetized rat

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Abstract
We tested the hypothesis that sensory nerves innervating blood vessels play a role in the local and systemic regulation of the cardiovascular and respiratory (CVR) systems. We measured CVR reflexes evoked by administration of anandamide (86 – 863 nmoles) and capsaicin (0.3 – 10 nmoles) into the hindlimb vasculature of anaesthetized rats. Anandamide and capsaicin each caused a rapid dose‐dependent reflex fall in blood pressure and an increase in ventilation when injected intra‐arterially into the hindlimb. Action of both agonists at the vanilloid receptor (VR1) on perivascular sensory nerves was investigated using capsazepine (1 mg kg−1i.a.) a competitive VR1 antagonist, ruthenium red (1 mg kg−1i.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−1i.a.) was used to determine agonist activity at the CB1receptor. Capsazepine, ruthenium red, or acute VR1 desensitization by capsaicin‐pretreatment, markedly attenuated the reflex CVR responses evoked by anandamide and capsaicin (Pt‐test). Blockade of CB1had no significant effect on the responses to anandamide. Local sectioning of the femoral and sciatic nerves attenuated CVR responses to anandamide and capsaicin (PviaVR1 located on sensory nerve endings within the hindlimb vasculature. British Journal of Pharmacology(2001)134, 655–663; doi:10.1038/sj.bjp.0704296