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

The effects of alpha,beta-,methylene-adenosine triphosphate, (alpha,beta-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 alpha,beta-methylene ATP (0.1 mumol/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 alpha,beta-methylene ATP (1 mumol/l). In WKY tail arteries, alpha,beta-methylene ATP (1 mumol/l) failed to significantly inhibit vasoconstrictor responses to electrical stimulation. In SHR tail arteries prelabelled with 3H-noradrenaline, alpha,beta-methylene ATP (1 mumol/l) did not inhibit the stimulation evoked release of tritium. However, at this concentration, alpha,beta-methylene ATP significantly antagonized the vasoconstrictor responses of SHR tail arteries induced by exogenous ATP (1 mumol/l), beta,gamma-methylene ATP (30 mumol/l), a stable agonist at P2-receptors, or 60 mmol/l KCl. These effects of alpha,beta-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 mumol/l), but were practically abolished by the addition of alpha,beta-methylene ATP (1 mumol/l). In tail arteries from WKY rats pretreated with reserpine, exposure to prazosin (0.1 mumol/l) further reduced the residual responses elicited by electrical field stimulation.(ABSTRACT TRUNCATED AT 250 WORDS)