Catecholamine release and potentiation of thromboxane A2 production by nicotine in the greyhound.
Thromboxane A2 was generated by infusing arachidonic acid (2.5 micrograms ml-1) into an extra-corporeal circuit of blood withdrawn from anaesthetized dogs, and assayed on a blood-bathed bioassay cascade of porcine and bovine coronary artery strips, chick rectum and rat stomach strip. All tissues except chick rectum were treated with phentolamine and propranolol to abolish direct effects of catecholamines. The arachidonate-induced contractions of artery strips were abolished by a thromboxane synthetase inhibitor UK-38485 (3 mg kg-1, i.v.), but were not altered by the 5-hydroxytryptamine antagonist ketanserin (10 microM) administered over the tissues. Intravenous infusion of adrenaline (0.2 and 0.4 micrograms kg-1 min-1) reversibly potentiated the coronary contractions produced by arachidonate, but did not alter contractions when applied directly over the bioassay tissues. Intra-aortic infusion of nicotine (5 or 10 micrograms kg-1 min-1) also increased the arachidonate-induced contractions of the bioassay tissues but only on those experiments where nicotine caused appreciable adrenaline release, as indicated by relaxation of chick rectum. Phenoxybenzamine (2 mg kg-1, i.v.) blocked the potentiation effect of adrenaline and nicotine on coronary contractions. The specific alpha 2-adrenoceptor antagonist, idazoxan (1 mg kg-1, i.v.), also blocked nicotine-induced potentiation of the contractions. These findings suggest that the ability of nicotine to potentiate thromboxane release from circulating platelets and blood cells is dependent upon the release of adrenaline, and probably involves an action on alpha-adrenoceptors of the circulating blood elements.
D000818:Animals; D016718:Arachidonic Acid; D001095:Arachidonic Acids / Q000494:pharmacology; D001794:Blood Pressure / Q000187:drug effects; D002395:Catecholamines / Q000378:metabolism*; D004146:Dioxanes / Q000494:pharmacology; D004285:Dogs; D004837:Epinephrine / Q000494:pharmacology; D005260:Female; D006339:Heart Rate / Q000187:drug effects; D019329:Idazoxan; D007093:Imidazoles / Q000494:pharmacology; D066298:In Vitro Techniques; D007650:Ketanserin; D008297:Male; D009538:Nicotine / Q000494:pharmacology*; D010643:Phenoxybenzamine / Q000494:pharmacology; D010880:Piperidines / Q000494:pharmacology; D013928:Thromboxane A2 / Q000096:biosynthesis*; D014661:Vasoconstriction / Q000187:drug effects
D001095:Arachidonic Acids; D002395:Catecholamines; D004146:Dioxanes; D007093:Imidazoles; D010880:Piperidines; D010643:Phenoxybenzamine; D016718:Arachidonic Acid; C039242:dazmegrel; D013928:Thromboxane A2; D009538:Nicotine; D007650:Ketanserin; D019329:Idazoxan; D004837:Epinephrine