DIADENOSINE POLYPHOSPHATES INCREASE CYTOSOLIC - CALCIUM AND ATTENUATEANGIOTENSIN-II-INDUCED CHANGES OF CALCIUM IN VASCULAR SMOOTH-MUSCLE CELLS

The effects of diadenosine tetraphosphate (AP(4)P), diadenosine pentap hosphate (AP(5)A), and diadenosine hexaphosphate (AP(6)A) on the cytos olic free calcium concentration ([Ca2+](i)) were evaluated in cultured rat vascular smooth muscle cells (VSMC) using the fluorescent dye tec hnique. A concentration-dependent increase of [Ca2+](i) by AP(4)A, AP( 5)A, and AP(6)A was observed in VSMC. Additions of 10 mu mol/l AP(4)A, AP(5)A, and AP(6)A significantly increased [Ca2+](i) in VSMC by 224 /- 62 nmol/l (n = 6; p < 0.01, 205 +/- 27 nmol/l (n = 14; p < 0.01), a nd 269 +/- 98 nmol/l (n = 5; p < 0.05), respectively. Additions of AP( 4)A, AP(5)A, and AP(6)A only 120 s prior to angiotensin II (Ang II) ad ministration significantly attenuated the Ang-II-induced changes of [C a2+](i) in VSMC from 1,053 +/- 174 nmol/l to 283 +/- 42 nmol/l, 591 +/ - 112 nmol/l, and 477 +/- 79 nmol/l, respectively (each p < 0.01 as co mpared to the control). The AP(6)A-induced changes of [Ca2+](i) were i nhibited by the blockers of P2 purinoceptors, suramin and pyridoxal-ph osphate-6-azophenyl-2',4'-disulphonic acid, but not by the inhibitor o f P2y purinoceptors, reactive blue. Adenosine triphosphate (ATP) also increased [Ca2+](i) in VSMC, whereas the purinoceptor P2x agonist, alp ha,beta-methylene-ATP, had no effect on [Ca2+](i) in VSMC. Therefore d iadenosine polyphosphates may induce changes of [Ca2+](i) by interacti ng with purinoceptors and may be involved in the local regulation of v ascular resistance evoked by the Ca2+-dependent contractile response o f VSMC.