Interaction of adenosine and prostacyclin in coronary flow regulation after myocardial ischemia.
The role of adenosine and prostacyclin in post-ischemic vasodilation was investigated using a model of sequential perfusion of two isolated hearts. Two guinea pig hearts were sequentially perfused (10 ml/min) without (control, n = 4) or with preceding 10-min ischemia (n = 6) of Heart I. Under control conditions no hemodynamic changes were observed in Heart II during sequential perfusion. After 10 min of ischemia of Heart I coronary perfusion pressure decreased by 23% in Heart II at the onset of sequential perfusion. Adenosine A1 and A2 receptor antagonists 1,3-dipropyl-8-cyclopentylxanthine (DPCPX) (2 microM) and 3,7-dimethyl-1-propargylxanthine (DMPX) (20 microM) infused simultaneously inhibited this decrease in coronary perfusion pressure by 74%, whereas indomethacin (5 microM) had no effect. DPCPX, DMPX and indomethacin in combination induced a significant increase in coronary perfusion pressure. Adenosine release (HPLC) into the coronary effluent after ischemia was significantly enhanced in the presence of indomethacin. These results suggest that after myocardial ischemia prostacyclin has an inhibitory effect on adenosine release.
Stangl
V
V
Medizinische Klinik und Poliklinik, Schwerpunkt Kardiologie, Angiologie, Pneumologie-Charité, Humboldt-Universität zu Berlin, Germany.
Frank
T M
TM
Schrör
K
K
Stangl
K
K
Baumann
G
G
Felix
S B
SB
D000241:Adenosine / Q000378:metabolism*; D000818:Animals; D016861:Cyclooxygenase Inhibitors / Q000494:pharmacology; D004347:Drug Interactions; D011464:Epoprostenol / Q000378:metabolism*; D006168:Guinea Pigs; D006321:Heart / Q000187:drug effects / Q000503:physiopathology*; D006439:Hemodynamics / Q000502:physiology; D066298:In Vitro Techniques; D007213:Indomethacin / Q000494:pharmacology; D017202:Myocardial Ischemia / Q000503:physiopathology*; D010477:Perfusion; D058915:Purinergic P1 Receptor Antagonists; D013805:Theobromine / Q000031:analogs & derivatives / Q000494:pharmacology; D013997:Time Factors; D014664:Vasodilation / Q000187:drug effects; D014970:Xanthines / Q000494:pharmacology
D016861:Cyclooxygenase Inhibitors; D058915:Purinergic P1 Receptor Antagonists; D014970:Xanthines; C057837:3,7-dimethyl-1-propargylxanthine; C051360:1,3-dipropyl-8-cyclopentylxanthine; D011464:Epoprostenol; D000241:Adenosine; D013805:Theobromine; D007213:Indomethacin