Differential effects of omega-conotoxin GVIA, tetrodotoxin and prolonged cold storage on purinergic and adrenergic transmission in isolated canine splenic artery

Abstract

Double-peaked vasoconstrictions (biphases of vasoconstrictions) were readily induced in the conditions of 30 s trains of pulses at 1 Hz in the isolated, perfused canine splenic artery. P2X purinoceptors have previously been shown to be involved mainfy in the first-peaked response and alpha1-adrenoceptors mostly in the second. The treatment with 10 nM omega-conotoxin GVIA (omega-CTX) produced a parallel inhibitory effect on the first- and second-peaked vasoconstrictor responses to nerve stimulation. A submaximal concentration of tetrodotoxin (TTX) (3 nM) did not affect the first peak of constriction, but strongly inhibited the second peak, although a larger dose of TTX (30 nM) abolished either the first- or second-peaked response. On the other hand, after cold storage at 4 degrees C for 7 days, the first-peaked vasoconstriction markedly decreased, whereas the second-peaked response was not significantly modified.

In conclusion: (1) omega-CTX-sensitive calcium channels may produce a parallel modulation of purinergic and adrenergic components of sympathetic cotransmission; (2) TTX-sensitive sodium channels may have a more important role in controlling the adrenergic rather than purinergic transmission; and (3) the function of purinergic transmission of sympathetic nerve might be affected more strongly than that of adrenergic transmission in the cold-stored canine splenic artery.