Vasoactivity of diadenosine polyphosphates in human small mesenteric resistance arteries.
Diadenosine polyphosphates (ApnA) (n = 3-6) induced vasoconstrictions in isolated human mesenteric resistance arteries (hMRAs) mounted in a microvessel myograph (rank order of potency: Ap5A > Ap6A > Ap4A > Ap3A). The contractile effects of ApnA in hMRA were similar to their effects in rat MRA investigated previously. ATP, ADP, AMP, and adenosine had less contractile potency than ApnA, suggesting that the observed effects were not induced by the degradation products of ApnA. Ap4A- and Ap5A-induced vasoconstriction was inhibited by pyridoxalphosphate-6-azophenyl-2',4'-disulfonic acid (PPADS) (P2X purinoceptor antagonist) but not by ADP3'5' (P2Y purinoceptor antagonist). Thus, this purinergic vasoconstriction of hMRA seems to be P2X but not P2Y purinoceptor-mediated. In precontracted hMRA all ApnA caused vasorelaxations but (in contrast to rat MRA) the potencies of the ApnA did not differ significantly from each other. The ApnA degradation products had less vasorelaxing potency than ApnA, demonstrating that the vasorelaxations can be ascribed to the ApnA themselves. Ap5A-induced vasorelaxation of hMRA could neither be inhibited with ADP3'5' nor with PPADS, which reveals a decisive difference to the rat MRA where the inhibitory profile demonstrated the importance of the P2Y purinoceptor for Ap5A-induced vasorelaxation. However, Ap4A-induced vasorelaxation in hMRA could be inhibited by ADP3'5'. These findings show that Ap4A-induced vasorelaxation in hMRA is due to P2Y purinoceptor activation, that Ap5A evokes vasorelaxation in hMRA via another mechanism than Ap4A, and that data derived from the animal model cannot be simply transferred to human conditions.
Steinmetz
Martin
M
Department of Internal Medicine D, University Clinics Münster, University of Münster, Albert-Schweitzer-Strasse 33, 48129 Münster, Germany. steinme@uni-muenster.de
Janssen
Ann-Kathrin
AK
Pelster
Franz
F
Rahn
Karl Heinz
KH
Schlatter
Eberhard
E
D000818:Animals; D015226:Dinucleoside Phosphates / Q000494:pharmacology*; D006801:Humans; D066298:In Vitro Techniques; D007700:Kinetics; D008638:Mesenteric Arteries / Q000187:drug effects / Q000502:physiology*; D009119:Muscle Contraction / Q000187:drug effects*; D051381:Rats; D014655:Vascular Resistance / Q000187:drug effects*
D015226:Dinucleoside Phosphates; C012275:P(1),P(5)-di(adenosine-5'-)pentaphosphate; C020733:diadenosine tetraphosphate; C011440:diadenosine triphosphate; C070070:diadenosine 5',5''''-P1,P6-hexaphosphate