DIADENOSINE POLYPHOSPHATES ACTION ON CALCIUM AND VESSEL CONTRACTION

The effects of the endogenous, platelet-derived vasoactive compounds, diadenosine tetraphosphate (AP(4)A), diadenosine pentaphosphate (AP(5) A), and diadenosine hexaphosphate (AP(6)A) on the vasoconstriction of isolated rat renal resistance vessels and rat aortic strips were measu red using a vessel myograph. In addition, the effects of AP(4)A, AP(5) A, and AP(6)A on the cytosolic free calcium concentration ([Ca2+](i)) were evaluated in cultured rat vascular smooth muscle cells (VSMC) usi ng the fluorescent dye technique. Diadenosine polyphosphates dose-depe ndently increased the force of renal resistance vessels and isolated a ortic ships. The administration of 10 mu mol/L AP(4)A, AP(5)A, or AP(6 )A significantly increased the force of isolated renal resistance vess els by 3.48 +/- 0.43 mN (n = 8), 2.14 +/- 0.40 mN (n = 12), or 2.70 +/ - 0.31 mN (n = 11, each P < .02 compared with resting tension), respec tively. The administration of 10 mu mol/L AP(4)A, AP(5)A, or AP(6)A si gnificantly increased the force of isolated aortic strips by 2.45 +/- 0.97 mNewton (n = 10), 2.70 +/- 0.30 mN (n = 6), or 1.48 +/- 0.20 mN ( each P < .01 compared with resting tension), respectively. The adminis tration of 10 mu mol/L AP(4)A, AP(5)A, or AP(6)A significantly increas ed [Ca2+](i) in VSMC to a peak concentration of 314 +/- 60 nmol/L (n = 6), 247 +/- 25 nmol/L (n = 15), or 332 +/- 100 nmol/L (n = 5), respec tively (each P < .01 compared with resting value). Both the diadenosin e polyphosphate-induced vasoconstriction and [Ca2+](i) increase was si gnificantly reduced in the absence of extracellular calcium or after a dministration of a specific inhibitor of P2 purinoceptors. It is concl uded that diadenosine polyphosphates increase [Ca2+](i) and hence caus e vessel constriction. (C) 1997 American Journal of Hypertension, Ltd.