Differential effects of ω-conotoxin GVIA and tetrodotoxin on vasoconstrictions evoked by electrical stimulation and nicotinic receptor stimulation in canine isolated, perfused splenic arteries

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Abstract
1 The effects of ω-conotoxin GVIA (ω-CgTX) and tetrodotoxin (TTX) on vasoconstrictions induced by acetylcholine (ACh) and nicotine were investigated and compared with those induced by periarterial electrical stimulation in the isolated and perfused canine splenic arteries. 2 ACh and nicotine at doses of 0.01 to 1 μmol constricted the splenic artery, dose-dependently. ACh induced consistent responses, but the vasoconstrictor responses to nicotine became significantly smaller with repeated administration of nicotine. 3 Periarterial electrical stimulation produced a vasoconstriction that was abolished by either TTX (30 nmol) or ω-CgTX (3 nmol), but the vasoconstrictor response to nicotine was not significantly affected by the same doses of TTX and ω-CgTX. Inhibitions by TTX and ω-CgTX of ACh-induced vasoconstrictions were small but statistically significant, showing that the percentage inhibition was less than 15%. TTX and ω-CgTX did not affect the vasoconstrictor responses to exogenous noradrenaline (NA). 4 ACh did not produce any vasoconstriction in the preparations treated either with α-adrenoceptor antagonists (10 μm bunazosin and 10 μm midaglizole) or with 30 μm guanethidine. NA-induced responses were abolished by α-adrenoceptor antagonists, but not affected by guanethidine treatment. 5 Vascular responses to ACh were completely inhibited by 1 μmol hexamethonium. In the preparations treated with 100 nmol nicotine, ACh did not produce any vasoconstriction. However, the NA-induced vasoconstriction was affected by neither hexamethonium nor nicotine treatment. 6 Atropine (1 μm) significantly inhibited but did not abolish the vasoconstrictor responses to ACh. The vascular responses to nicotine and NA were also significantly inhibited by atropine treatment. 7 These results indicate that (1) ACh constricts the splenic artery through the activation of presynaptic nicotinic receptors present on the sympathetic nerves; (2) differential effects of TTX and ω-CgTX on the vascular responses to ACh and nicotine, and to electrical stimulation suggest that the receptor-operated ion channels are mainly responsible for NA release induced by nicotinic receptor stimulation, but N-type VOCCs are responsible for that by electrical stimulation; (3) atropine may have an inhibitory action on nicotine-related responses, in addition to its inhibitory action on NA.