A cannabinoid receptor, sensitive to O-1918, is involved in the delayed hypotension induced by anandamide in anaesthetized rats.
OBJECTIVE
Intravenous injection of the endocannabinoid anandamide induces complex cardiovascular changes via cannabinoid CB(1), CB(2) and vanilloid TRPV1 receptors. Recently, evidence has been accumulating that in vitro, but not in vivo, anandamide relaxes blood vessels, via an as yet unidentified, non-CB(1) vascular cannabinoid receptor, sensitive to O-1918 (1,3-dimethoxy-5-2-[(1R,6R)-3-methyl-6-(1-methylethenyl)-2-cyclohexen-1-yl]-benzene). We here examined whether the anandamide-induced hypotension in urethane-anaesthetized rats was also mediated via a non-CB(1) vascular cannabinoid receptor.


METHODS
Effects of two antagonists (O-1918 and cannabidiol) of the non-CB(1) vascular cannabinoid receptor on anandamide-induced changes in mean, systolic and diastolic blood pressure (MBP, SBP, DBP), mesenteric (MBF) and renal (RBF) blood flow and heart rate (HR) in urethane-anaesthetized rats was examined.


RESULTS
In anaesthetized rats, anandamide (1.5-3 micromol.kg(-1)) and its stable analogue methanandamide (0.5 micromol.kg(-1)) caused a delayed and prolonged decrease in MBP, SBP, DBP, MBF and RBF by about 10-30% of the respective basal values without changing HR. In pithed rats, anandamide (3 micromol.kg(-1)) decreased blood pressure by about 15-20% of the basal value without affecting HR, MBF and RBF. All vascular changes were reduced by about 30-70% by cannabidiol and O-1918 (3 micromol.kg(-1), each).


CONCLUSIONS
Non-CB(1) cannabinoid vascular receptors, sensitive to O-1918, contribute to the hypotensive effect of anandamide in anaesthetized rats. Activation of these receptors may be therapeutically important as the endocannabinoid system could be activated as a compensatory mechanism in various forms of hypertension.
Zakrzeska
Agnieszka
A
Zakład Fizjologii Doświadczalnej, Uniwersytet Medyczny w Białymstoku, Białystok, Poland.
Schlicker
Eberhard
E
Baranowska
Marta
M
Kozłowska
Hanna
H
Kwolek
Grzegorz
G
Malinowska
Barbara
B
D000758:Anesthesia / Q000379:methods*; D000818:Animals; D000840:Anisoles / Q000494:pharmacology*; D001095:Arachidonic Acids / Q000494:pharmacology*; D001794:Blood Pressure / Q000187:drug effects; D002185:Cannabidiol / Q000494:pharmacology; D063387:Cannabinoid Receptor Antagonists; D003510:Cyclohexanes / Q000494:pharmacology*; D063388:Endocannabinoids; D007022:Hypotension / Q000139:chemically induced*; D008297:Male; D053284:Polyunsaturated Alkamides / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar; D012079:Renal Circulation / Q000187:drug effects; D013152:Splanchnic Circulation / Q000187:drug effects
C552735:1,3-dimethoxy-5-methyl-2-(3-methyl-6-(1-methylethenyl)-2-cyclohexen-1-yl)benzene; D000840:Anisoles; D001095:Arachidonic Acids; D063387:Cannabinoid Receptor Antagonists; D003510:Cyclohexanes; D063388:Endocannabinoids; D053284:Polyunsaturated Alkamides; C088155:methanandamide; D002185:Cannabidiol; C078814:anandamide