Diadenosine Polyphosphates' Action on Calcium and Vessel Contraction

Abstract

The effects of the endogenous, platelet-derived vasoactive compounds, diadenosine tetraphosphate (AP4A), diadenosine pentaphosphate (AP5A), and diadenosine hexaphosphate (AP6A) on the vasoconstriction of isolated rat renal resistance vessels and rat aortic strips were measured using a vessel myograph. In addition, the effects of AP4A, AP5A, and AP6A on the cytosolic free calcium concentration ([Ca2+]i) were evaluated in cultured rat vascular smooth muscle cells (VSMC) using the fluorescent dye technique. Diadenosine polyphosphates dose-dependently increased the force of renal resistance vessels and isolated aortic strips. The administration of 10 mumol/L AP4A, AP5A, or AP6A significantly increased the force of isolated renal resistance vessels 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 < .01 compared with resting tension), respectively. The administration of 10 micromol/L AP4A, AP5A, or AP6A significantly 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 administration of 10 micromol/L AP4A, AP5A, or AP6A significantly increased [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), respectively (each P < .01 compared with resting value). Both the diadenosine polyphosphate-induced vasoconstriction and [Ca2+]i increase was significantly reduced in the absence of extracellular calcium or after administration of a specific inhibitor of P2 purinoceptors. It is concluded that diadenosine polyphosphates increase [Ca2+]i and hence cause vessel constriction.

HDL induces NO-dependent vasorelaxation via the lysophospholipid receptor S1P3

“…(13,14). The wall tension of the vasculature was measured in rat and mouse aortas using established methodology (15). Aortae from both species displayed reliable NO-related responses.…”

Diadenosine pentaphosphate vasodilates the forearm vascular bed: Inhibition by theophylline and augmentation by dipyridamole

“…Our observation that AP 5 A reduces forearm vascular tone at physiologically relevant concentrations 31 is at variance with a human in vitro study that showed vasoconstriction of isolated umbilical arteries in response to AP 5 A 32 and with animal in vitro studies that demonstrated vasoconstriction in isolated renal resistance arteries, 2,3,9,12 isolated perfused mesenteric arteries, 14 and isolated rat aortic strips. 33 However, more recently a vasodilator response to AP 5 A has also been observed in animal preparations in vitro. 15,34 How can these discrepancies be explained?…”

PROGRESS IN UREMIC TOXIN RESEARCH: Dinucleoside Polyphosphates and Uremia

“…Stimulation of P2X receptors induces an influx of monovalent and divalent cations into the cytosol. The increased concentration of these ions triggers a depolarisation of vascular smooth muscle cells and hence vasoconstriction (33). Eight P2X receptors have been described, named P2X 1 -P2X 8 (34).…”