Vol. 283, Issue 2, 548-556, 1997

Diadenosine Polyphosphates Directly Relax Porcine Coronary Arterial Smooth Muscle¹

Rieko Sumiyoshi, Junji Nishimura, Junya Kawasaki, Sei Kobayashi, Shosuke Takahashi² and Hideo Kanaide

Division of Molecular Cardiology, Research Institute of Angiocardiology, Faculty of Medicine, Kyushu University, Fukuoka 812-82, Japan

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_nA) diadenosine 5,5-P¹,P⁴-tetraphosphate (AP₄A) and diadenosine 5,5-P¹,P⁵-pentaphosphate (AP₅A). AP_nA 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⁺⁺. AP_nA 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⁺⁺, AP_nA 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.