The contribution of VR1 and CB1 receptors and the role of the afferent vagal pathway in modelling of cardio-respiratory effects of anandamide in rats.
Anaesthetized and spontaneously breathing rats were used to study the cardio-respiratory effects of intravenous anandamide administration. To investigate the role of particular levels of the afferent pathway in this response rats were challenged with bolus injection of anandamide (1 mg kg(-1)) into the femoral vein while intact, following bilateral superior laryngeal nerves (SLNs) section and after midcervical vagotomy. To test the hypothesis that the activation of the vanilloid receptors (VR1) as well as cannabinoid receptors (CB1) contributes to the anandamide-induced response administrations of anandamide were preceded by nonselective VR1 antagonist ruthenium red or selective CB1 antagonist AM281. Anandamide evoked apnoea of mean duration of 4.84+/-0.75 s in all animals while intact which was shortened by subsequent neurotomies, after SLNs section to 3.3+/-0.57 s (P<0.05) and after midcervical vagi section to 1.99+/-0.24 s (P<0.01). In post-apnoeic breathing tidal volume (V(T)) was reduced in all neural states. Anandamide evoked hypotension in the intact and SLNs neurotomized rats. Midcervical vagotomy reduced this fall in blood pressure. Both antagonists ruthenium red and AM281 eliminated post-anandamide apnoea and hypotension but had no effect on post-apnoeic depression of V(T). Subsequent SLNs and cervical vagi sections did not eliminate but only reduced post-anandamide depression of breathing. Midcervical vagotomy lessened anandamide-induced hypotension. Apnoeic and hypotensive response to anandamide was mediated by both VR1 and CB1 receptors. Post-anandamide decline of V(T) might depend on different type of receptors.
Kopczyńska
Beata
B
Laboratory of Respiratory Reflexes, PAS Medical Research Center, 5 Pawińskiego St., 02-106 Warsaw, Poland. kopczynb@cmdik.pan.pl
D000344:Afferent Pathways / Q000502:physiology; D000818:Animals; D001049:Apnea / Q000139:chemically induced / Q000378:metabolism; D001095:Arachidonic Acids / Q000008:administration & dosage*; D001794:Blood Pressure / Q000187:drug effects; D002121:Calcium Channel Blockers / Q000008:administration & dosage*; D063385:Cannabinoid Receptor Modulators / Q000008:administration & dosage*; D063388:Endocannabinoids; D006321:Heart / Q000187:drug effects*; D007022:Hypotension / Q000139:chemically induced / Q000378:metabolism; D007275:Injections, Intravenous; D008297:Male; D053284:Polyunsaturated Alkamides / Q000008:administration & dosage*; D051381:Rats; D017208:Rats, Wistar; D043884:Receptor, Cannabinoid, CB1 / Q000819:agonists / Q000502:physiology*; D012119:Respiration / Q000187:drug effects*; D012430:Ruthenium Red / Q000494:pharmacology; D050916:TRPV Cation Channels / Q000819:agonists / Q000037:antagonists & inhibitors / Q000502:physiology*; D014628:Vagotomy; D014630:Vagus Nerve / Q000187:drug effects / Q000502:physiology*
D001095:Arachidonic Acids; D002121:Calcium Channel Blockers; D063385:Cannabinoid Receptor Modulators; D063388:Endocannabinoids; D053284:Polyunsaturated Alkamides; D043884:Receptor, Cannabinoid, CB1; D050916:TRPV Cation Channels; C494484:TRPV1 receptor; D012430:Ruthenium Red; C078814:anandamide