Titre du document / Document title

Importance of imidazoline-preferring receptors in the cardiovascular actions of chronically administered moxonidine, rilmenidine and clonidine in conscious rabbits

Auteur(s) / Author(s)

PARKIN Monique L. ⁽¹⁾ ; GODWIN Shirley J. ⁽¹⁾ ; HEAD Geoffrey A. ⁽¹⁾ ;

Affiliation(s) du ou des auteurs / Author(s) Affiliation(s)

⁽¹⁾ Neuropharmacology Laboratory, Baker Heart Research Institute, Melbourne, AUSTRALIE

Résumé / Abstract

Objective To determine the involvement of central imidazoline receptors in the cardiovascular actions of the chronically administered antihypertensive agents moxonidine, rilmenidine and clonidine. Design and methods In 21 rabbits with implanted fourth-ventricular catheters, we investigated the central effects of three cumulative doses of an I₁-imidazoline/α₂-adrenoceptor antagonist, efaroxan, and of an α₂-adrenoceptor antagonist, 2-methoxyidazoxan (2-MI), on the changes in blood pressure and heart rate (HR) elicited by chronic subcutaneous administration of moxonidine, rilmenidine and clonidine, after 1 and 3 weeks of treatment A low, medium and high dose of 2-MI was matched to three doses of efaroxan, such that each produced equal reversal of the hypotension induced by fourth-ventricular α-methyldopa and hence produced a similar degree of α₂-adrenoceptor blockade. Results Clonidine and moxonidine, at doses of 1 mg/kg per day, and rilmenidine at 5 mg/kg per day, produced sustained reductions in mean arterial pressure of 13 ± 3, 15 ± 2 and 13 ± 2 mmHg, respectively over the 3-week treatment period, but did not alter HR. Central administration of efaroxan on day 9 and day 23 of treatment produced a greater increase in blood pressure than did 2-MI with all three antihypertensive agents. Blood pressure reached levels that were significantly above the original control values. By contrast, the α₂-adrenoceptor antagonist 2-MI only induced a rebound blood pressure effect in clonidine- and to a lesser extent in rilmenidine-treated rabbits. Both efaroxan and 2-MI produced a similar degree of tachycardia in moxonidine-, rilmenidine- and clonidine-treated animals. Conclusions The greater effect of efaroxan compared to the α₂-adrenoceptor antagonist 2-MI suggests that the hypotension induced by chronic subcutaneous administration of moxonidine, rilmenidine and clonidine is mediated predominantly via an action on central imidazoline receptors. Furthermore, all agents showed a propensity to produce rebound hypertension with imidazoline receptor blockade. However, only clonidine showed a rebound phenomenon when challenged by acute central α₂-adrenoceptor blockade.

Revue / Journal Title

Journal of hypertension   ISSN 0263-6352   CODEN JOHYD3 

Source / Source

2003, vol. 21, n^o1, pp. 167-178 [12 page(s) (article)] (37 ref.)

Langue / Language

Anglais

Editeur / Publisher

Lippincott Williams & Wilkins, Hagerstown, MD, ETATS-UNIS  (1983) (Revue)

Mots-clés anglais / English Keywords

Vertebrata ; Mammalia ; Lagomorpha ; Antihypertensive agent ; Animal ; Rabbit ; Biological activity ; Heart rate ; Arterial pressure ; Imidazoline receptor ; Clonidine ; Rilmenidine ; Moxonidine ;

Mots-clés français / French Keywords

Vertebrata ; Mammalia ; Lagomorpha ; Oxazoline dérivé ; Antihypertenseur ; Animal ; Lapin ; Activité biologique ; Rythme cardiaque ; Pression artérielle ; Récepteur imidazoline ; Clonidine ; Rilménidine ; Moxonidine ;

Mots-clés espagnols / Spanish Keywords

Vertebrata ; Mammalia ; Lagomorpha ; Antihipertensivo ; Animal ; Conejo ; Actividad biológica ; Ritmo cardíaco ; Presión arterial ; Receptor imidazolina ; Clonidina ; Rilmenidina ; Moxonidina ;

Mots-clés d'auteur / Author Keywords

moxonidine ; rilmenidine ; clonidine ; efaroxan ; 2-methoxyidazoxan ; imidazoline receptors ; α2-adrenoceptors ; blood pressure ; heart rate ;

Localisation / Location

INIST-CNRS, Cote INIST : 20680, 35400010392208.0170