title: Central benzodiazepine involvement in clonidine cardiovascular actions.
abstract: It is well known that the GABAergic and noradrenergic systems play an important role in blood pressure and heart rate regulation. Benzodiazepines and beta-carbolines, respectively, increase or decrease the probability of chloride-channel opening induced by GABA. The aim of this study was to determine, in conscious rats, the interaction existing between the central alpha2-adrenoceptor stimulation induced by clonidine and the facilitation or impairment of benzodiazepine receptor activity through the administration of either diazepam, a benzodiazepine receptor agonist, or methyl 6,7-dimethoxy-4-ethyl-beta-carboline-3-carboxylate (DMCM), an inverse benzodiazepine agonist. Clonidine (5-10 microg, intracerebroventricularly) reduced heart rate and increased mean blood pressure by activation of central alpha2-adrenoceptors. Diazepam (2 mg/kg, intravenously (i.v.)) induced an increase in heart rate, while DMCM (0.3 mg/kg, i.v.) elicited a bradycardic effect. The bradycardic effects induced by both clonidine and DMCM were antagonized by the prior administration of methylatropine (1.5 mg/kg, i.v.). DMCM (0.3 mg/kg, i.v.) prevented the clonidine effects on heart rate and mean blood pressure, while diazepam (2 mg/kg, i.v.) failed to modify these effects. Our results suggest that the bradycardic effects of clonidine are mediated by a vagal stimulation and are related to the activation of a GABAergic pathway.
authors.affiliation: Cátedra de Farmacología, Facultad de Farmacia y Bioquímica, Universidad de Buenos Aires, Argentina. jcastro@huemul.ffyb.uba.ar
authors.forename: J L
authors.initials: JL
authors.lastname: Castro
authors.forename: D
authors.initials: D
authors.lastname: Ricci
authors.forename: C A
authors.initials: CA
authors.lastname: Taira
authors.forename: A
authors.initials: A
authors.lastname: Ramirez
mesh_terms: D058647:Adrenergic alpha-2 Receptor Agonists; D000316:Adrenergic alpha-Agonists / Q000494:pharmacology; D000317:Adrenergic alpha-Antagonists / Q000494:pharmacology; D000818:Animals; D001286:Atropine Derivatives / Q000494:pharmacology; D001794:Blood Pressure / Q000187:drug effects*; D002243:Carbolines / Q000494:pharmacology; D002317:Cardiovascular Agents / Q000494:pharmacology*; D003000:Clonidine / Q000494:pharmacology*; D003975:Diazepam / Q000494:pharmacology; D005442:Flumazenil / Q000494:pharmacology; D018757:GABA Modulators / Q000494:pharmacology; D058785:GABA-A Receptor Agonists; D006339:Heart Rate / Q000187:drug effects*; D007262:Infusions, Intravenous; D007276:Injections, Intraventricular; D008297:Male; D011224:Prazosin / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D018341:Receptors, Adrenergic, alpha-2 / Q000502:physiology*; D011963:Receptors, GABA-A / Q000502:physiology*; D013238:Stereotaxic Techniques; D013997:Time Factors; D015016:Yohimbine / Q000494:pharmacology
chemical_list: D058647:Adrenergic alpha-2 Receptor Agonists; D000316:Adrenergic alpha-Agonists; D000317:Adrenergic alpha-Antagonists; D001286:Atropine Derivatives; D002243:Carbolines; D002317:Cardiovascular Agents; D018757:GABA Modulators; D058785:GABA-A Receptor Agonists; D018341:Receptors, Adrenergic, alpha-2; D011963:Receptors, GABA-A; C034818:methyl 6,7-dimethoxy-4-ethyl-beta-carboline-3-carboxylate; D015016:Yohimbine; D005442:Flumazenil; C006649:methylatropine; D003000:Clonidine; D003975:Diazepam; D011224:Prazosin