Diadenosine polyphosphates' action on calcium and vessel contraction.
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.
Tepel
M
M
Universitätsklinik Marienhospital, Medizinische Klinik I, Ruhr-Universität-Bochum, Herne, Germany.
Jankowski
J
J
Schlüter
H
H
Bachmann
J
J
van der Giet
M
M
Ruess
C
C
Terliesner
J
J
Zidek
W
W
D000818:Animals; D002118:Calcium / Q000378:metabolism*; D015226:Dinucleoside Phosphates / Q000494:pharmacology*; D066298:In Vitro Techniques; D008297:Male; D009131:Muscle, Smooth, Vascular / Q000187:drug effects* / Q000378:metabolism; D051381:Rats; D011921:Rats, Inbred WKY; D014661:Vasoconstriction / Q000187:drug effects*
D015226:Dinucleoside Phosphates; C012275:P(1),P(5)-di(adenosine-5'-)pentaphosphate; C020733:diadenosine tetraphosphate; C070070:diadenosine 5',5''''-P1,P6-hexaphosphate; D002118:Calcium