Role of VR1 and CB1 receptors in modelling of cardio-respiratory response to arvanil, an endocannabinoid and vanilloid hybrid, in rats.
Cardio-respiratory effects of an intravenous injection of arvanil, a structural "hybrid" between capsaicin and anandamide, were investigated in 40 urethane-chloralose anaesthetized and spontaneously breathing rats. In the group of rats the response to arvanil was checked to establish the appropriate dose of the drug. To analyze the pattern of the cardio-respiratory effects rats were challenged with bolus injection of arvanil (0.8 mg kg(-1)) into the femoral vein. Administration of the drug evoked, in all tested rats, a significant increase of tidal volume (V(T)) and diaphragm activity, hypertension coupled with a fall in respiratory rate (f). To test the contribution of vanilloid (VR1) and cannabinoid (CB1) receptors to post-arvanil response, administrations of the drug were preceded by nonselective VR1 antagonist ruthenium red, selective VR1 antagonist SB366791 or selective CB1 antagonist AM281. All antagonists eliminated an increase in V(T) but failed to block the hypertension evoked by arvanil. Ruthenium red as well as SB366791 abolished post-arvanil fall in respiratory rate. The rise of diaphragm activity was totally eliminated by ruthenium red and markedly reduced by SB366791. AM281 blockade of post-arvanil changes in f and diaphragm activity was ineffective. These findings indicated that the post-arvanil rise of V(T) was mediated by both VR1 and CB1 receptors. Only vanilloid receptors were involved in the increase of diaphragm activity and decrease of respiratory frequency. Hypertensive response to arvanil might depend on different types of receptors.
Laboratory of Respiratory Reflexes, PAS Medical Research Center, 5 Pawińskiego Street, Warsaw, Poland. kopczynb@cmdik.pan.pl
Beata
B
Kopczyńska
D000813:Anilides / Q000494:pharmacology; D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D063385:Cannabinoid Receptor Modulators / Q000009:adverse effects*; D002211:Capsaicin / Q000009:adverse effects / Q000031:analogs & derivatives*; D002934:Cinnamates / Q000494:pharmacology; D004195:Disease Models, Animal; D063388:Endocannabinoids; D006973:Hypertension / Q000139:chemically induced* / Q000150:complications / Q000378:metabolism / Q000503:physiopathology; D007275:Injections, Intravenous; D008297:Male; D009025:Morpholines / Q000494:pharmacology; D011720:Pyrazoles / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D043884:Receptor, Cannabinoid, CB1 / Q000037:antagonists & inhibitors / Q000378:metabolism*; D012119:Respiration / Q000187:drug effects; D012120:Respiration Disorders / Q000139:chemically induced* / Q000150:complications / Q000378:metabolism / Q000503:physiopathology; D012430:Ruthenium Red / Q000494:pharmacology; D050916:TRPV Cation Channels / Q000037:antagonists & inhibitors / Q000378:metabolism*; D013990:Tidal Volume / Q000187:drug effects
D000813:Anilides; D063385:Cannabinoid Receptor Modulators; D002934:Cinnamates; D063388:Endocannabinoids; D009025:Morpholines; C477659:N-(3-methoxyphenyl)-4-chlorocinnamanilide; D011720:Pyrazoles; D043884:Receptor, Cannabinoid, CB1; D050916:TRPV Cation Channels; C493922:Trpv1 protein, rat; C121153:arvanil; D012430:Ruthenium Red; D002211:Capsaicin; C109925:AM 281