DIADENOSINE POLYPHOSPHATE-INDUCED INCREASE IN CYTOSOLIC-FREE CALCIUM IN VASCULAR SMOOTH-MUSCLE CELLS

Objective: To evaluate the effects of two new endogenous vasoconstrict ing substances, diadenosine pentaphosphate (AP(5)A) and diadenosine he xaphosphate (AP(6)A) on the cytosolic free calcium concentration in va scular smooth muscle cells. Methods: Spectrofluorophotometric measurem ents of cytosolic Ca2+ were conducted in monolayers of cultured rat va scular smooth muscle cells using the calcium-sensitive fluorescent dye fura-2. Results: The resting Ca2+ concentration in vascular smooth mu scle cells was 80 +/- 5 nmol/l (mean +/- SEM; n = 39). The addition of 10 mu mol/l AP(5)A or AP(6)A significantly increased Ca2+ in vascular smooth muscle cells to 248 +/- 55 and 358 +/- 124 nmol/l, respectivel y. The sustained increase in Ca2+ after administration of AP(5)A or AP (6)A was 143 +/- 40 and 148 +/- 57 nmol/l, respectively. Diadenosine p olyphosphates induce a transplasmamembrane calcium influx as detected by experiments in the absence of external calcium or by using the mang anese quenching technique to report unidirectional calcium fluxes. The effects of diadenosine polyphosphates were compared to those of the w ell known vasoconstrictor angiotensin II, which increased Ca2+ in vasc ular smooth muscle cells by 1053 +/- 174 nmol/l. Conclusions: Diadenos ine polyphosphates increase Ca2+ in vascular smooth muscle cells, ther eby regulating the contractility of vascular smooth muscle and subsequ ently blood pressure.