Effects and interactions of natural cannabinoids on the isolated heart.
A Langendorff perfused rat heart preparation was designed to process dose-response effects of cardioactive drugs on rate, coronary flow, and supraaortic differential pressure (delta P; an index of cardiac performance). In this preparation, delta 9- -tetrahydrocannabinol (THC) 2 X 10(-6) M to 10(-5) M induces in the isolated perfused rat heart a biphasic increase in rate (maximal at 8 X 10(-6) M). Tachycardia is associated with decreases in (delta P) and no change or decreased coronary flow. Cardiac toxicity is observed with 3 X 10(-5) M. Cannabidiol (CBD) at concentrations of 9 X 10(-6) M to 10(-4) M has limited effect on rate while increasing delta P and coronary flow. Cannabinol (CBN) 8 X 10(-6) M to 3 X 10(-4) M depresses rate and delta P while coronary flow remains constant. Simultaneous equimolar administration of THC with CBD antagonizes or mitigates the cardiac effects of THC on rate, delta P, and coronary flow.
D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D002185:Cannabidiol / Q000494:pharmacology / Q000633:toxicity; D002186:Cannabinoids / Q000494:pharmacology* / Q000633:toxicity; D002187:Cannabinol / Q000494:pharmacology / Q000633:toxicity; D002302:Cardiac Output / Q000187:drug effects; D003326:Coronary Circulation / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D006321:Heart / Q000187:drug effects* / Q000503:physiopathology; D006339:Heart Rate / Q000187:drug effects; D006439:Hemodynamics / Q000187:drug effects*; D051381:Rats; D011919:Rats, Inbred Strains; D013610:Tachycardia / Q000139:chemically induced
D002186:Cannabinoids; D002185:Cannabidiol; D002187:Cannabinol