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Respective contributions of α‐adrenergic and non‐adrenergic mechanisms in the hypotensive effect of imidazoline‐like drugs
Author(s) -
Bruban Véronique,
Feldman Josiane,
Greney Hugues,
Dontenwill Monique,
Schann Stephan,
Jarry Christian,
Payard Marc,
Boutin Jean,
Scalbert Elizabeth,
Pfeiffer Bruno,
Renard Pierre,
Vanhoutte Paul,
Bousquet Pascal
Publication year - 2001
Publication title -
british journal of pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.432
H-Index - 211
eISSN - 1476-5381
pISSN - 0007-1188
DOI - 10.1038/sj.bjp.0704080
Subject(s) - imidazoline receptor , clonidine , agonist , rauwolscine , adrenergic , pharmacology , adrenergic agonist , antagonist , guanfacine , endocrinology , stimulation , medicine , chemistry , receptor , prazosin
The hypotensive effect of imidazoline‐like drugs, such as clonidine, was first attributed to the exclusive stimulation of central α 2 ‐adrenoceptors (α 2 ARs). However, a body of evidence suggests that non‐adrenergic mechanisms may also account for this hypotension. This work aims (i) to check whether imidazoline‐like drugs with no α 2 ‐adrenergic agonist activity may alter blood pressure (BP) and (ii) to seek a possible interaction between such a drug and an α 2 ARs agonist α‐methylnoradrenaline (α‐MNA). We selected S23515 and S23757, two imidazoline‐like drugs with negligible affinities and activities at α 2 ARs but with high affinities for non‐adrenergic imidazoline binding sites (IBS). S23515 decreased BP dose‐dependently (−27±5% maximal effect) when administered intracisternally (i.c.) to anaesthetized rabbits. The hypotension induced by S23515 (100 μg kg −1 i.c.) was prevented by S23757 (1 mg kg −1 i.c.) and efaroxan (10 μg kg −1 i.c.), while these compounds, devoid of haemodynamic action by themselves, did not alter the hypotensive effect of α‐MNA (3 and 30 μg kg −1 i.c.). Moreover, the α 2 ARs antagonist rauwolscine (3 μg kg −1 i.c.) did not prevent the effect of S23515. Finally, whilst 3 μg kg −1 of S23515 or 0.5 μg kg −1 of α‐MNA had weak hypotensive effects, the sequential i.c. administration of these two drugs induced a marked hypotension (−23±2%). These results indicate that an imidazoline‐like drug with no α 2 ‐adrenergic properties lowers BP and interacts synergistically with an α 2 ARs agonist.British Journal of Pharmacology (2001) 133 , 261–266; doi: 10.1038/sj.bjp.0704080

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