Central and peripheral components of the pressor effect of anandamide in urethane-anaesthetized rats.
1. We wanted to search for the mechanism(s) responsible for the brief pressor response induced by anandamide in urethane-anaesthetized rats. 2. The anandamide-induced pressor effect was not modified by the antagonists of cannabinoid CB(1) and vanilloid TRPV(1) receptors, SR 141716A (3 micromol kg(-1)) and capsazepine (1 micromol kg(-1)), respectively, by bilateral vagotomy and by pithing. Replacement of urethane by pentobarbitone virtually abolished the pressor effect of anandamide, both in pithed and vagotomized and in 'intact' rats (i.e. not treated in this manner). 3. The pressor effect of anandamide was reduced by the nonselective TRPV family inhibitor ruthenium red (3 micromol kg(-1)) and by the blocker of L-type calcium channels nifedipine (1 micromol kg(-1)), both in pithed urethane-anaesthetized rats and in 'intact' urethane-anaesthetized rats. The nonselective beta-adrenoceptor antagonist propranolol (0.1 or 0.3 micromol kg(-1)) and the nonselective NMDA receptor antagonist MK-801 (1 micromol kg(-1)) diminished the anandamide-induced vasopressor response in 'intact' but not in pithed rats. The inhibitory effect of propranolol in 'intact' rats was mimicked by the beta(2)-adrenoceptor antagonist ICI 118551 (1 micromol kg(-1)), but not by the beta(1)-adrenoceptor antagonist CGP 20712 (1 micromol kg(-1)). 4. The present study revealed that two mechanisms may be responsible for the anandamide-induced pressor response in urethane-anaesthetized rats. The first involves the central nervous system (probably the medulla oblongata) and is sensitive to propranolol and MK-801. The second, which is located peripherally (most probably in blood vessels), is sensitive to nifedipine, ruthenium red and pentobarbitone and, hence, probably represents a Ca(2+)-dependent mode of action.
Kwolek
Grzegorz
G
Zakład Fizjologii Doświadczalnej, Akademia Medyczna w Białymstoku, ul. Mickiewicza 2A, 15-089 Białystok 8, Poland.
Zakrzeska
Agnieszka
A
Schlicker
Eberhard
E
Göthert
Manfred
M
Godlewski
Grzegorz
G
Malinowska
Barbara
B
D000319:Adrenergic beta-Antagonists / Q000494:pharmacology; D000758:Anesthesia; D000818:Animals; D001095:Arachidonic Acids / Q000494:pharmacology*; D001794:Blood Pressure / Q000187:drug effects*; D002121:Calcium Channel Blockers / Q000494:pharmacology*; D002490:Central Nervous System / Q000187:drug effects*; D003655:Decerebrate State; D016291:Dizocilpine Maleate / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D004347:Drug Interactions; D063388:Endocannabinoids; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology; D006339:Heart Rate / Q000187:drug effects; D007473:Ion Channels / Q000037:antagonists & inhibitors; D008297:Male; D017933:Peripheral Nervous System / Q000187:drug effects*; D053284:Polyunsaturated Alkamides; D051381:Rats; D017208:Rats, Wistar; D043884:Receptor, Cannabinoid, CB1 / Q000037:antagonists & inhibitors; D011955:Receptors, Drug / Q000037:antagonists & inhibitors; D050916:TRPV Cation Channels; D014520:Urethane
D000319:Adrenergic beta-Antagonists; D001095:Arachidonic Acids; D002121:Calcium Channel Blockers; D063388:Endocannabinoids; D018691:Excitatory Amino Acid Antagonists; D007473:Ion Channels; D053284:Polyunsaturated Alkamides; D043884:Receptor, Cannabinoid, CB1; D011955:Receptors, Drug; D050916:TRPV Cation Channels; C493922:Trpv1 protein, rat; D014520:Urethane; D016291:Dizocilpine Maleate; C078814:anandamide