Role of cannabinoid receptors in the regulation of cardiac contractility during ischemia/reperfusion.
We studied the effect of selective ligands of cannabinoid (CB) receptors on contractility of isolated Langendorff-perfused rat heart under conditions of 45-min total ischemia and 30-min reperfusion. Perfusion with a solution containing selective CB receptor agonist HU-210 for 10 min before ischemia increased the severity of reperfusion contractile dysfunction. This drug decreased left ventricular developed pressure and maximum rates of contraction and relaxation, but had no effect on heart rate and end-diastolic pressure. The negative inotropic effect of the drug was transitory and disappeared after 5-min reperfusion. Pretreatment with selective CB1 receptor antagonist SR141716A and selective CB2 receptor antagonist SR144528 had no effect on heart rate and myocardial contractility during reperfusion. Our results indicate that stimulation of CB receptors can increase the degree of reperfusion-induced cardiac contractile dysfunction. However, endogenous cannabinoids are not involved in the development of myocardial contractile dysfunction during ischemia/reperfusion of the isolated heart.
Maslov
L N
LN
Institute of Cardiology, Siberian Division of the Russian Academy of Medical Sciences, Tomsk. maslov@cardio.tsu.ru
Lasukova
O V
OV
Krylatov
A V
AV
Hanus
L O
LO
Pertwee
R
R
Ivanchuk
I I
II
Crowford
D
D
D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D001892:Camphanes / Q000494:pharmacology; D013759:Dronabinol / Q000031:analogs & derivatives / Q000494:pharmacology; D006339:Heart Rate / Q000187:drug effects; D066298:In Vitro Techniques; D008297:Male; D009200:Myocardial Contraction / Q000502:physiology*; D015428:Myocardial Reperfusion Injury / Q000503:physiopathology*; D010880:Piperidines / Q000494:pharmacology; D011720:Pyrazoles / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D043882:Receptors, Cannabinoid / Q000187:drug effects / Q000502:physiology*; D000077285:Rimonabant
D001892:Camphanes; D010880:Piperidines; D011720:Pyrazoles; D043882:Receptors, Cannabinoid; C110630:SR 144528; D013759:Dronabinol; C062018:HU 211; D000077285:Rimonabant