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.