Rilmenidine acts as a partial agonist at prejunctional alpha 2-adrenoceptors in guinea-pig atria.
1. The present study was carried out to determine whether rilmenidine, a recently introduced antihypertensive agent which acts on alpha 2-adrenoceptors, has partial agonist activity on prejunctional alpha 2-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 mumol/l) 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 alpha 2-adrenoceptor antagonists, idazoxan (0.1 and 0.3 mumol/l) and rauwolscine (0.3 mumol/l) whereas it was not affected by the alpha 1-adrenoceptor antagonist prazosin (0.1 mumol/l). 4. On the other hand, rilmenidine (1 mumol/l) enhanced noradrenaline release evoked by long trains (150 and 300 pulses) of stimulation and this effect was also abolished by idazoxan (0.1 mumol/l). 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 alpha 2-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 alpha 2-adrenoceptors in guinea-pig atria.
Li
C G
CG
Department of Pharmacology, University of Melbourne, Parkville, Victoria, Australia.
Rand
M J
MJ
D000316:Adrenergic alpha-Agonists / Q000494:pharmacology*; D000818:Animals; D000959:Antihypertensive Agents / Q000494:pharmacology*; D016275:Atrial Function; D004558:Electric Stimulation; D005260:Female; D006168:Guinea Pigs; D008297:Male; D009638:Norepinephrine / Q000378:metabolism*; D010080:Oxazoles / Q000494:pharmacology*; D011942:Receptors, Adrenergic, alpha / Q000187:drug effects* / Q000378:metabolism; D000077769:Rilmenidine
D000316:Adrenergic alpha-Agonists; D000959:Antihypertensive Agents; D010080:Oxazoles; D011942:Receptors, Adrenergic, alpha; D000077769:Rilmenidine; D009638:Norepinephrine