Prominent sympathetic purinergic vasoconstriction in the rabbit splenic artery: potentiation by 2,2′-pyridylisatogen tosylate

Abstract

1. Vasoconstrictions induced by transmural electrical field stimulation were frequency-dependent from 2 to 32 Hz in the rabbit isolated splenic artery. All contractions were abolished in the presence of tetrodotoxin 1 μM or guanethidine 100 μM. Stimulation at a frequency of more than 32 Hz induced both neurogenic and myogenic responses.

2. Prazosin (1 μM) did not significantly affect vascular contractions to electrical stimulation. Desensitization of P_2X-purinoceptors with α,β-methylene ATP (α,β-meATP, 3 μM) abolished the contractions to stimulation at 2–8 Hz and inhibited more than 80% of the vascular response at 16 Hz, but it did not significantly change the responses at 32 Hz. Contractile responses at 32 Hz were inhibited by a combination of prazosin and α,β-meATP. Effects of pyridoxal-phosphate-6-azophenyl-2′, 4′-disulphonic acid tetrasodium salt (a selective P_2X-purinoceptor antagonist) and suramin (a competitive P₂-purinoceptor antagonist) on the neurogenic responses were investigated in this study.

3. 2,2′-Pyridylisatogen tosylate (PIT, 0.3–3 μM) significantly potentiated the vasoconstrictions to electrical stimulation at 2–32 Hz in a concentration-dependent manner. Potentiated responses were restored to the control level 30 min after washing. Concentration-dependent response curves for noradrenaline (NA) or α,β-meATP were not significantly changed by 3 μM PIT, and vasoconstriction by adenosine 5′-triphosphate (ATP, 300 μM) was unaffected by PIT. Coomassie brilliant blue-G (1 μM), which shares the potentiating effect on a recombinant P_2Y-purinoceptor with PIT (King et al., 1996), did not inhibit or potentiate the purinergically-mediated component of the response to sympathetic nerve stimulation. The selective α₂-adrenoceptor antagonist yohimbine (1 μM) also potentiated the vascular responses to electrical stimulation.

4. The present results indicate that ATP evokes postjunctional contractile responses at low and high frequency electrical stimulation of sympathetic nerves supplying the rabbit splenic artery. PIT potentiates the responses to sympathetic (purinergic) nerve stimulation; this appears to be mainly via prejunctional rather than postjunctional actions.

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