Inhibition of noradrenaline release by ω‐conotoxin GVIA in the rat tail artery

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Abstract
1 The perivascular nerves of isolated tail arteries from Wistar rats were stimulated with field pulses (1Hz, 2 pulses, every 2 min). ω-Conotoxin 10 nmol l−1 depressed neurogenically mediated contractions, but did not influence the contractions to noradrenaline 0.1–0.3 μmol 1−1. 2 The inhibitory effect of ω-conotoxin was concentration-dependent (IC50 = 3.8 nmol l−1). It did not reach a steady-state during 30 min incubation and could not be reversed upon subsequent washout for another 60 min. 3 A gradual increase in the Ca2+ concentration of the medium from 1.25 mmol l−1 to 10 mmol 1−1 enhanced vasoconstriction and attenuated the action of ω-conotoxin 10 nmol l−1. When a low stimulation intensity (120 mA) was used at high external Ca2+ (10 mmol l−1), similar contractile responses were obtained as under normal conditions (200mA current, 2.5 mmol l−1 Ca2+). However, the inverse relationship between the effect of the toxin and external Ca2+ remained unchanged. 4 The time-course and degree of the inhibition by ω-conotoxin 3 nmol l−1 was identical in tail arteries of spontaneously hypertensive rats (SHR) and their normotensive controls (WKY). 5 When tail arteries of Wistar rats were preincubated with [3H]-noradrenaline, field stimulation (0.4 Hz, 24 pulses, every 16 min) evoked tritium overflow and vasoconstriction. ω-Conotoxin 30 nmol l−1 inhibited both responses to a similar extent. 6 Our results suggest that ω-conotoxin selectively blocks Ca2+ channels in the terminals of perivascular nerves and thereby reduces the release, but not the contractile effect of the sympathetic transmitter.
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