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

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 ETB 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 x 10(-6) M), and was not modified either by the antagonist of endothelin ETA receptors cyclo(D-alpha-aspartyl-L-prolyl-D-valyl-L-leucyl-D-tryptophyl) (BQ-123, 10(-7)-3 x 10(-6) M) or the agonist of endothelin ETB 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-(N-(alpha-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 x 10(-6) M), BQ-123 (3 x 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 ETB receptors, which may inhibit noradrenaline release from perivascular sympathetic nerves. (C) 1999 Elsevier Science B.V. All rights reserved.