Interaction between central alpha 1- and alpha 2-adrenoceptors on sympathetic tone in rats.
The interaction between piperoxan and alpha 2-agonists on sympathetic tone was studied in rats. The sympatho-inhibitory effect of alpha 2-agonists (clonidine, guanfacine, B-HT 933) was assessed by recording heart rate in normotensive bilaterally-vagotomized rats. Clonidine (3 micrograms/kg, i.c.v.) and B-HT 933 (100 micrograms/kg, i.c.v.) induced a bradycardia which was fully reversed by piperoxan (30 micrograms/kg, i.c.v.). However, in rats treated with guanfacine, piperoxan induced a partial recovery of the bradycardic effect. The injection of a small dose of the specific alpha 1-adrenoceptor blocking drug, AR-C 239 (10 micrograms/kg, i.c.v.) which, by itself did not modify heart rate, completely inhibited the reversal effect of piperoxan in rats treated with clonidine, B-HT 933 or guanfacine. In rat brainstem membranes, B-HT 933 was found to bind to both alpha 1- and alpha 2-adrenoceptors and was as potent as clonidine in competing for alpha 1-sites bound by [3H]prazosin. On the other hand, in bilaterally vagotomized rats, piperoxan (30 micrograms/kg, i.c.v.) induced an increase in blood pressure and heart rate which was inhibited by previous administration of AR-C 239 (10 micrograms/kg, i.c.v.). These data suggest that, by inhibiting central alpha 2-adrenoceptors, piperoxan unmasks central alpha 1-adrenoceptor stimulation by endogenous catecholamines leading to an increase in the sympathetic tone, but a full recovery in heart rate could be observed only with the mixed alpha 1- and alpha 2-adrenoceptor agonists, clonidine and B-HT 933. In addition, these data further indicate that alpha 1-adrenoceptors are implicated in a tonic control of the sympathetic nerve activity in normotensive rats.
D000818:Animals; D001381:Azepines / Q000494:pharmacology; D001921:Brain / Q000502:physiology*; D003000:Clonidine / Q000494:pharmacology; D016316:Guanfacine; D006146:Guanidines / Q000494:pharmacology; D006339:Heart Rate / Q000187:drug effects; D007276:Injections, Intraventricular; D008297:Male; D010648:Phenylacetates / Q000494:pharmacology; D010883:Piperoxan / Q000494:pharmacology; D051381:Rats; D011919:Rats, Inbred Strains; D011942:Receptors, Adrenergic, alpha / Q000187:drug effects*; D013564:Sympathetic Nervous System / Q000187:drug effects*; D014628:Vagotomy
D001381:Azepines; D006146:Guanidines; D010648:Phenylacetates; D011942:Receptors, Adrenergic, alpha; D016316:Guanfacine; D010883:Piperoxan; C015603:azepexole; D003000:Clonidine