Pharmacologic modulation of ATP release from isolated rat hearts in response to vasoconstrictor stimuli using a continuous flow technique.
A new method is described for continuously recording ATP release in isolated perfused hearts by a bioluminescence technique that makes possible the study of the dynamics of ATP release in terms of coronary vascular regulation. Infusion of exogenous ATP in isolated perfused rat hearts resulted in a clearance of 97.8 +/- 0.5% in one pass through the heart. Short-term infusion of either leukotriene (LT) D4 (0.02-0.5 nmol) or norepinephrine (NE; 0.06-0.6 mumol) released significant quantities of ATP from isolated rat hearts in a dose-dependent manner. In contrast, equipotent vasoconstrictor doses of arginine vasopressin (AVP; 20 and 60 microU) failed to release ATP. The amount of ATP released by LTD4 and NE declined by 50 to 60% with each consecutive challenge. LTD4-induced vasoconstriction and ATP release were totally abolished by the LT receptor antagonist FPL-55,712, whereas the NE-induced coronary vasoconstriction and ATP release were totally blocked by the alpha adrenergic blocking agent phentolamine. The coronary vasoconstriction induced by NE was followed by a slight coronary vasodilation, which was inhibited by the beta adrenergic blocking agent timolol without influencing ATP release. The LTD4- and NE-induced release of ATP appears to be receptor mediated and may play a role in the regulation of coronary vascular tone.
D000255:Adenosine Triphosphate / Q000378:metabolism*; D000818:Animals; D001127:Arginine Vasopressin / Q000494:pharmacology; D001794:Blood Pressure; D002867:Chromones / Q000494:pharmacology; D006145:Guanethidine / Q000494:pharmacology; D006321:Heart / Q000187:drug effects*; D009206:Myocardium / Q000378:metabolism*; D009638:Norepinephrine / Q000494:pharmacology; D010477:Perfusion; D010646:Phentolamine / Q000494:pharmacology; D051381:Rats; D013189:SRS-A / Q000494:pharmacology; D012601:Scopolamine / Q000494:pharmacology; D013564:Sympathetic Nervous System / Q000187:drug effects / Q000378:metabolism
D002867:Chromones; D013189:SRS-A; D001127:Arginine Vasopressin; D000255:Adenosine Triphosphate; C006312:FPL 55712; D012601:Scopolamine; D009638:Norepinephrine; D010646:Phentolamine; D006145:Guanethidine