Medullary hypotensive effect of endothelin1 in anaesthetized animals

In anaesthetized animals, systemic injection of ET1 at doses from 3 to 100 ng.kg-1 provoked only a transient hypotensive effect. At 300 ng.kg-1 we observed the classical biphasic effect, consisting of a transient lowering of the arterial pressure followed by a long-lasting hypertensive effect. Direct injection of the peptide into the vertebral artery of anaesthetized animals only affected arterial pressure (AP) when the blood-brain barrier was permeabilised. Under these conditions, a dose-dependent decrease in AP was observed, which was not associated with a significant effect on the heart rate. Micro-injections of the peptide in the medullary nucleus reticularis lateralis area (NRL), a medullary vasopressive centre, at doses of 30 to 60 ng.kg-1 led to a significant reduction in mean arterial pressure (MAP) (17 +/- 4% and 36.5 +/- 6%) respectively without a significant change in heart rate. These effects lasted less than 2 hours. These results suggest a possible role of ET1 as a neuromodulator involved in the central regulation of vasomotor tone, in the NRL region.