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 (AP(n)A) diadenosine 5',5'''-P-1,P-4-tetraphosphate (AP(4)A) and diad enosine 5',5'''-P-1,P-5-pentaphosphate (AP(5)A). AP(n)A concentration- dependently inhibited the sustained elevations of [Ca++](i) and force induced by U-46619, a thromboxane A(2) analog, in the presence of extr acellular Ca++. AP(n)A shifted the [Ca++](i)-force relation curves of contractions induced by various concentrations of high K+ to the right . The AP(4)A-induced decreases in [Ca++](i) and force were largely att enuated by tetrabutylammonium. The AP(4)A-induced decreases in force w ere attenuated by 4-aminopyridine and charybdotoxin. The AP(5)A-induce d decreases in [Ca++](i) and force were attenuated by tetrabutylammoni um, 4-aminopyridine and charybdotoxin. In the absence of extracellular Ca++, AP(n)A did not inhibit the transient elevations of [Ca++](i) in duced by histamine or caffeine. Both AP(4)A and AP(5)A increased intra cellular cAMP content. We thus conclude that AP(4)A and AP(5)A relax t he porcine coronary artery by decreasing [Ca++](i), possibly through t he activation of K+ channels, but not through inhibition of intracellu lar Ca++ release and by decreasing the Ca++ sensitivity of the contrac tile machinery. These effects were considered to be mediated by cAMP.