Differential effects of ?-?-methylene ATP on responses to nerve stimulation in SHR and WKY tail arteries

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Abstract
The effects of α,β-methylene-adenosine triphosphate, (α,β-methylene ATP, a P2-receptor desensitising agent) have been evaluated on vasoconstrictor responses elicited by exogenous agonists or electrical field stimulation in isolated perfused SHR or WKY tail arteries and on tritium release elicited by electrical field stimulation in SHR-tail arteries pre-labeled with 3H-noradrenaline. Exposure to α,β-methylene ATP (0.1 μmol/l) significantly inhibited vasoconstrictor responses to electrical field stimulation in SHR tail arteries. These inhibitory effects were not further increased at a higher concentration of α,β-methylene ATP (1 μmol/l). In WKY tail arteries, α,β-methylene ATP (1 μmol/l) failed to significantly inhibit vasoconstrictor responses to electrical stimulation. In SHR tail arteries prelabelled with 3H-noradrenaline, α,β-methyleneATP (1 μmol/l) did not inhibit the stimulation evoked release of tritium. However, at this concentration, α,β-methylene ATP significantly antagonized the vasoconstrictor responses of SHR tail arteries induced by exogenous ATP (1 μmol/l), β,γ-methylene ATP (30 μmol/l), a stable agonist at P2-receptors, or 60 mmol/l KCl. These effects of α,β-methylene ATP on contractile responses to KCl were not observed in WKY-tail arteries. In tail arteries obtained from reserpine pretreated SHR, despite a 85–95% decrease in endogenous noradrenaline tissue content, the vasoconstrictor responses induced by periarterial field stimulation were greatly diminished, but not abolished. These residual responses to periarterial field stimulation were not antagonized by prazosin (0.1 μmol/l), but were practically abolished by the addition of α,β-methylene ATP (1 μmol/l). In tail arteries from WKY rats pretreated with reserpine, exposure to prazosin (0.1 μmol/l) further reduced the residual responses elicited by electrical field stimulation. In these WKY-tail arteries, addition of α,β-methylene ATP (1 μmol/l) did not further inhibit the remaining vasoconstrictor response obtained in the presence of prazosin. While our results suggest a significantly greater cotransmitter role for ATP with noradrenaline in tail arteries of SHR compared with control normotensive WKY rats, additional effects of α,β-methylene ATP not involving P2 receptors cannot be entirely excluded.