Basal inhibitory action of endogenous endothelin on the sympathetic contraction in the isolated rat tail artery

Abstract

In order to test whether endogenous endothelin modulates the sympathetic vasoconstriction, arterial segments, 2 mm long, from rat tail artery were mounted in organ baths for isometric tension recording. Electrical field stimulation (2–8 Hz, 0.2 ms, 70 V during 1 s) produced frequency-dependent arterial contraction (maximal contraction 770±49 mg) that was nearly abolished (over 95% reduction) by tetrodotoxin (10 −6 M) or phentolamine (10 −6 M). This contraction was increased by pretreatment with the antagonist of endothelin ET B receptors N-( N-( N-(2,6-dimethyl-1-piperidinyl)carbonyl)-4-methyl- l-leucyl)-1-(methoxycarbonyl)- d-tryptophyl) d-norleucine (BQ-788, 10 −7–3×10 −6 M), and was not modified either by the antagonist of endothelin ET A receptors cyclo( d-α-aspartyl- l-prolyl- d-valyl- l-leucyl- d-tryptophyl) (BQ-123, 10 −7–3×10 −6 M) or the agonist of endothelin ET B receptors endothelin-1 (8–21), N-Suc-(Glu 9, Ala 11,15) (IRL-1620, 10 −8–10 −7 M). The potentiating effect of BQ-788 was not modified in arterial segments without endothelium or pretreated with the inhibitor of nitric oxide synthesis N W-nitro- l-arginine ( l-NA, 10 −4 M) or with the inhibitor of endothelin converting enzyme N-(α-rhamnopyranosyloxy-hydroxyphosphinyl)-leu-trp (phosphoramidon, 10 −4 M). Exogenous noradrenaline (10 −9–10 −4 M) produced concentration-dependent arterial contractions that were not modified by BQ-788 (3×10 −6 M), BQ-123 (3×10 −6 M) or IRL-1620 (10 −7 M). Therefore, an inhibitory action of endogenous endothelin on sympathetic vasoconstriction may be present under basal conditions. This inhibition could be produced by endothelin through activation of prejunctional endothelin ET B receptors, which may inhibit noradrenaline release from perivascular sympathetic nerves.