Potent effects of AP3A and AP4A on coronary resistance and autacoid release of intact rabbit hearts.
We investigated effects of platelet-derived dinucleotides diadenosine 5',5"'-P1,P3-triphosphate (AP3A) and diadenosine 5',5"'-P1,P4-tetraphosphate (AP4A) on coronary vasculature. In isolated rabbit hearts, saline perfused at constant flow (36 +/- 3 ml/min), AP3A and AP4A induced dose-dependent decreases in coronary perfusion pressure. Dose-effect curves of AP3A [-log M mean effective concentration (EC50) 6.2 +/- 0.1] and AP4A (EC50 6.4 +/- 0.2) were identical and not significantly different from those of adenosine, ADP, and ATP (n = 4-8). There were, however, distinct differences between both dinucleotides: pretreatment with endothelium-derived relaxing factor (EDRF)-inhibitors oxyhemoglobin (6 microM, n = 6) and NG-nitro-L-arginine (30 microM, n = 6) significantly reduced AP4A-induced dilation by 44 and 42% but did not affect vasomotor effects of AP3A or of sodium nitroprusside, adenosine, ATP, and ADP. Concentration of the stable hydrolysis product of prostaglandin (PG)I2, 6-keto-PGF1 alpha, increased by 173 +/- 25% in coronary effluent (n = 23) during infusion of AP3A (1 microM). This increase was significantly higher than during infusion of equimolar concentrations of AP4A (38 +/- 10%), ATP (23 +/- 5%), adenosine (20 +/- 10%), or an equimolar combination of AMP and ADP (52 +/- 25%), the hydrolysis products of AP3A. Luminometric and high-performance liquid chromatography analysis showed a nearly complete (94 +/- 3%) degradation of ATP during passage through the coronary bed while significant amounts of AP3A (31 +/- 5%) and AP4A (33 +/- 6%) remained uncleaved.(ABSTRACT TRUNCATED AT 250 WORDS)
Pohl
U
U
Department of Applied Physiology, University of Freiburg, Federal Republic of Germany.
Ogilvie
A
A
Lamontagne
D
D
Busse
R
R
D000255:Adenosine Triphosphate / Q000378:metabolism; D000818:Animals; D003326:Coronary Circulation / Q000187:drug effects*; D015226:Dinucleoside Phosphates / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D004355:Drug Stability; D011464:Epoprostenol / Q000378:metabolism*; D005260:Female; D008297:Male; D009206:Myocardium / Q000378:metabolism*; D009569:Nitric Oxide / Q000037:antagonists & inhibitors / Q000378:metabolism*; D011817:Rabbits; D014655:Vascular Resistance / Q000187:drug effects*; D014665:Vasodilator Agents / Q000494:pharmacology
D015226:Dinucleoside Phosphates; D014665:Vasodilator Agents; D009569:Nitric Oxide; C020733:diadenosine tetraphosphate; C011440:diadenosine triphosphate; D000255:Adenosine Triphosphate; D011464:Epoprostenol