Actions of endothelin on adrenergic neuroeffector junction

The effect of endothelin, a novel vasoconstrictor peptide, on the adrenergic neuroeffector junction was investigated in isolated perfused rat mesenteric arteries. The vasoconstrictor responses to periarterial nerve stimulation and exogenous noradrenaline were determined. Infusion of endothelin-1 (10(-14) to 10(-8) mol/l) increased the baseline perfusion pressure dose dependently. Subpressor doses of endothelin-1 (10(-11) and 10(-10) mol/l) enhanced the pressor response to noradrenaline, and 10(-12) to 10(-10) mol/l endothelin-1 attenuated the pressor response to periarterial nerve stimulation. Endothelin-1 also caused a dose-dependent inhibition of [3H]-noradrenaline release during the periarterial nerve stimulation. However, higher doses of endothelin-1 (3 x 10(-10) to 10(-8) mol/l) enhanced the pressor response to stimulation. These results suggest that endothelin potentiates adrenergic vasoconstriction postjunctionally while it inhibits adrenergic neurotransmission. Thus endothelin may have actions on the neuroeffector junction in addition to its direct vasoconstricting effect.