PROMINENT SYMPATHETIC PURINERGIC VASOCONSTRICTION IN THE RABBIT SPLENIC ARTERY - POTENTIATION BY 2,2'-PYRIDYLISATOGEN TOSYLATE

1 Vasoconstrictions induced by transmural electrical field stimulation were frequency-dependent from 2 to 32 Hz in the rabbit isolated splen ic artery. All contractions were abolished in the presence of tetrodot oxin 1 mu M or guanethidine 100 mu M. Stimulation at a frequency of mo re than 32 Hz induced both neurogenic and myogenic responses. 2 Prazos in (1 mu M) did not significantly affect vascular contractions to elec trical stimulation. Desensitization of P-2X-purinoceptors with alpha,b eta-methylene ATP (alpha,beta-meATP, 3 mu M) abolished the contraction s 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 combinati on of prate sin and alpha,beta-meATP. Effects of pyridoxal-phosphate-6 -azophenyl-2', 4'-disulphonic acid tetrasodium salt (a selective P-2X- purinoceptor antagonist) and suramin (a competitive P-2-purinoceptor a ntagonist) on the neurogenic responses were investigated in this study . 3 2,2'-Pyridylisatogen tosylate (PIT, 0.3-3 mu M) significantly pote ntiated 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 res ponse curves for noradrenaline (NA) or alpha,beta-meATP were not signi ficantly changed by 3 mu M PIT, and vasoconstriction by adenosine 5'-t riphosphate (ATP, 300 mu M) was unaffected by PIT. Coomassie brilliant blue-G (1 mu M), which shares the potentiating effect on a recombinan t P-2Y-purinoceptor with PIT (King et al., 1996), did not inhibit or p otentiate the purinergically-mediated component of the response to sym pathetic nerve stimulation. The selective alpha(2)-adrenoceptor antago nist yohimbine (1 mu M) also potentiated the vascular responses to ele ctrical stimulation.4 The present results indicate that ATP evokes pos tjunctional 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 stim ulation; this appears to be mainly via prejunctional rather than postj unctional actions.