RILMENIDINE ACTS AS A PARTIAL AGONIST AT PREJUNCTIONAL α2‐ADRENOCEPTORS IN GUINEA‐PIG ATRIA

Publisher Website
Google Scholar
Abstract
SUMMARY: 1. The present study was carried out to determine whether rilmenidine, a recently introduced antihypertensive agent which acts on α2‐adrenoceptors, has partial agonist activity on prejunctional α2‐adrenoceptors in guinea‐pig atria.2. Isolated preparations of guinea‐pig atria were incubated with [3H]‐noradrenaline and the efflux of radioactivity induced by stimulation of intramural sympathetic nerves was used as an index of release of transmitter noradrenaline.3. Rilmenidine (1 μmol/1) inhibited noradrenaline release evoked by short trains (five, 20 and 50 pulses) of sympathetic nerve stimulation and this inhibitory effect of rilmenidine was antagonized by the α2‐adrenoceptor antagonists, idazoxan (0.1 and 0.3 umol/1) and rauwolscine (0.3 umol/1) whereas it was not affected by the α1‐adrenoceptor antagonist prazosin (0.1 μmol/1).4. On the other hand, rilmenidine (1 μmol/1) enhanced noradrenaline release evoked by long trains (150 and 300 pulses) of stimulation and this effect was also abolished by idazoxan (0.1 μmol/1).5. These findings suggest that the effects of rilmenidine on transmitter release depend on the degree of auto‐inhibition: when the concentration of noradrenaline in the biophase of the prejunctional α2‐adrenoceptors is low, rilmenidine acts as an agonist, but when the concentration is high it acts as an antagonist. Thus, rilmenidine, like clonidine, is a partial agonist on prejunctional α2‐adrenoceptors in guinea‐pig atria.

This publication has 0 references indexed in Scilit: