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

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 (IC 50 = 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 Ca 2+ 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 Ca 2+ (10 mmol l −1 ), similar contractile responses were obtained as under normal conditions (200mA current, 2.5 mmol l −1 Ca 2+ ). However, the inverse relationship between the effect of the toxin and external Ca 2+ 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 [ 3 H]‐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 Ca 2+ channels in the terminals of perivascular nerves and thereby reduces the release, but not the contractile effect of the sympathetic transmitter.