Diadenosine polyphosphates directly relax porcine coronary arterial smooth muscle.
By use of front-surface fluorometry and fura-2-loaded medial strips of the porcine coronary artery, cytosolic Ca++ concentration ([Ca++]i) and force development were monitored simultaneously to determine the mechanisms of vasorelaxation induced by the diadenosine polyphosphates (APnA) diadenosine 5',5'''-P1, P4-tetraphosphate (AP4A) and diadenosine 5',5'''-P1,P5-pentaphosphate (AP5A). APnA concentration-dependently inhibited the sustained elevations of [Ca++]i and force induced by U-46619, a thromboxane A2 analog, in the presence of extracellular Ca++. APnA shifted the [Ca++]i-force relation curves of contractions induced by various concentrations of high K+ to the right. The AP4A-induced decreases in [Ca++]i and force were largely attenuated by tetrabutylammonium. The AP4A-induced decreases in force were attenuated by 4-aminopyridine and charybdotoxin. The AP5A-induced decreases in [Ca++]i and force were attenuated by tetrabutylammonium, 4-aminopyridine and charybdotoxin. In the absence of extracellular Ca++, APnA did not inhibit the transient elevations of [Ca++]i induced by histamine or caffeine. Both AP4A and AP5A increased intracellular cAMP content. We thus conclude that AP4A and AP5A relax the porcine coronary artery by decreasing [Ca++]i, possibly through the activation of K+ channels, but not through inhibition of intracellular Ca++ release and by decreasing the Ca++ sensitivity of the contractile machinery. These effects were considered to be mediated by cAMP.
Sumiyoshi
R
R
Division of Molecular Cardiology, Research Institute of Angiocardiology, Faculty of Medicine, Kyushu University, Fukuoka 812-82, Japan.
Nishimura
J
J
Kawasaki
J
J
Kobayashi
S
S
Takahashi
S
S
Kanaide
H
H
D019796:15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5,13-dienoic Acid / Q000494:pharmacology; D000818:Animals; D002110:Caffeine / Q000494:pharmacology; D002118:Calcium / Q000378:metabolism; D003331:Coronary Vessels / Q000187:drug effects*; D000242:Cyclic AMP / Q000032:analysis; D006152:Cyclic GMP / Q000032:analysis; D015226:Dinucleoside Phosphates / Q000494:pharmacology*; D006632:Histamine / Q000494:pharmacology; D066298:In Vitro Techniques; D009131:Muscle, Smooth, Vascular / Q000187:drug effects* / Q000502:physiology; D026902:Potassium Channel Blockers; D013552:Swine; D014664:Vasodilation / Q000187:drug effects*
D015226:Dinucleoside Phosphates; D026902:Potassium Channel Blockers; D002110:Caffeine; C012275:P(1),P(5)-di(adenosine-5'-)pentaphosphate; C020733:diadenosine tetraphosphate; D019796:15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5,13-dienoic Acid; D006632:Histamine; D000242:Cyclic AMP; D006152:Cyclic GMP; D002118:Calcium