Anandamide induces cardiovascular and respiratory reflexes via vasosensory nerves in the anaesthetized rat.
1. 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. 2. 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. 3. Action of both agonists at the vanilloid receptor (VR1) on perivascular sensory nerves was investigated using capsazepine (1 mg kg(-1) i.a.) a competitive 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(1) receptor. 4. Capsazepine, ruthenium red, or acute VR1 desensitization by capsaicin-pretreatment, markedly attenuated the reflex CVR responses evoked by anandamide and capsaicin (P< 0.05; paired Student's t-test). Blockade of CB(1) had no significant effect on the responses to anandamide. 5. Local sectioning of the femoral and sciatic nerves attenuated CVR responses to anandamide and capsaicin (P< 0.05). Vagotomy or carotid sinus sectioning 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-arterially into the rat hindlimb. These responses appear to be mediated reflexly via VR1 located on sensory nerve endings within the hindlimb vasculature.
Smith
P J
PJ
Department of Neuroscience, University of Edinburgh Medical School, 1 George Square, Edinburgh EH8 9JZ. Paula.Smith@ed.ac.uk
McQueen
D S
DS
D000777:Anesthetics / Q000008:administration & dosage / Q000494:pharmacology*; D000818:Animals; D001095:Arachidonic Acids / Q000494:pharmacology*; D001794:Blood Pressure / Q000187:drug effects / Q000502:physiology; D002121:Calcium Channel Blockers / Q000494:pharmacology*; D002211:Capsaicin / Q000494:pharmacology; D002319:Cardiovascular System / Q000187:drug effects*; D063388:Endocannabinoids; D008297:Male; D009475:Neurons, Afferent / Q000187:drug effects* / Q000502:physiology; D053284:Polyunsaturated Alkamides; D012123:Pulmonary Ventilation / Q000187:drug effects / Q000502:physiology; D051381:Rats; D017208:Rats, Wistar; D012018:Reflex / Q000187:drug effects; D012137:Respiratory System / Q000187:drug effects*
D000777:Anesthetics; D001095:Arachidonic Acids; D002121:Calcium Channel Blockers; D063388:Endocannabinoids; D053284:Polyunsaturated Alkamides; D002211:Capsaicin; C078814:anandamide