Paradoxical effects of endothelin on cardiovascular noradrenergic neurotransmission.

1. Pre- and postjunctional effects of endothelin (1-10 nmol/L) have been studied in the rabbit isolated ear artery and in rat isolated atria. 2. Endothelin produced concentration-dependent increases in arterial perfusion pressure, and had positive chronotropic and inotropic effects in rat atria. 3. Vasoconstrictor responses of the arteries to sympathetic nerve stimulation were reduced by 1 nmol/L endothelin and abolished by 10 nmol/L endothelin. In rat atria, the chronotropic responses to nerve stimulation were markedly reduced by 10 nmol/L endothelin. 4. In rabbit ear artery, vasoconstrictor responses to noradrenaline were enhanced by 1 nmol/L endothelin, but were reduced by 10 nmol/L endothelin. In rat atria, endothelin reduced the chronotropic response to isoprenaline. 5. Endothelin (10 nmol/L) increased the stimulation-induced release of radioactivity in arteries and atria labelled with [3H]-noradrenaline by 91% and 23%, respectively. 6. The pre- and postjunctional effects of endothelin persisted in both arterial and atrial preparations for at least 30 min after its removal.