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Titolo:
Respective contributions of alpha-adrenergic and non-adrenergic mechanismsin the hypotensive effect of imidazoline-like drugs
Autore:
Bruban, V; Feldman, J; Greney, H; Dontenwill, M; Schann, S; Jarry, C; Payard, M; Boutin, J; Scalbert, E; Pfeiffer, B; Renard, P; Vanhoutte, P; Bousquet, P;
Indirizzi:
Univ Strasbourg 1, Lab Neurobiol & Pharmacol Cardiovasc, Fac Med, F-67000 Strasbourg, France Univ Strasbourg 1 Strasbourg France F-67000 , F-67000 Strasbourg, France Univ Bordeaux 2, Chim Phys Lab, Fac Pharmaceut Sci, F-33076 Bordeaux, France Univ Bordeaux 2 Bordeaux France F-33076 ut Sci, F-33076 Bordeaux, France Fac Pharm, Lab Chim Pharmaceut, F-31400 Toulouse, France Fac Pharm Toulouse France F-31400 m Pharmaceut, F-31400 Toulouse, France Inst Rech Int Servier, F-92415 Courbevoie, France Inst Rech Int Servier Courbevoie France F-92415 92415 Courbevoie, France
Titolo Testata:
BRITISH JOURNAL OF PHARMACOLOGY
fascicolo: 2, volume: 133, anno: 2001,
pagine: 261 - 266
SICI:
0007-1188(200105)133:2<261:RCOAAN>2.0.ZU;2-2
Fonte:
ISI
Lingua:
ENG
Soggetto:
ROSTRAL VENTROLATERAL MEDULLA; ALPHA-2-ADRENOCEPTOR ANTAGONIST; ANTIHYPERTENSIVE ACTION; BINDING-SITES; HUMAN BRAIN; RECEPTORS; CLONIDINE; RILMENIDINE; MOXONIDINE; BOVINE;
Keywords:
sympathetic nervous system; hypertension; imidazoline-like drugs; alpha(2)-adrenoceptors; alpha-methylnoradrenaline; clonidine;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Life Sciences
Citazioni:
26
Recensione:
Indirizzi per estratti:
Indirizzo: Bousquet, P Univ Strasbourg 1, Lab Neurobiol & Pharmacol Cardiovasc, Fac Med, 11 Rue Humann, F-67000 Strasbourg, France Univ Strasbourg 1 11 Rue Humann Strasbourg France F-67000 nce
Citazione:
V. Bruban et al., "Respective contributions of alpha-adrenergic and non-adrenergic mechanismsin the hypotensive effect of imidazoline-like drugs", BR J PHARM, 133(2), 2001, pp. 261-266

Abstract

1 The hypotensive effect of imidazoline-like drugs, such as clonidine, wasfirst attributed to the exclusive stimulation of central aa-adrenoceptors (alpha (2)ARs).2 However, a body of evidence suggests that non-adrenergic mechanisms may also account for this hypotension.3 This work aims (i) to check whether imidazoline-llike drugs with no alpha (2)-adrenergic agonist activity may alter blood pressure (BP) and (ii) toseek a possible interaction between such a drug and an alpha (2)ARs agonist alpha -methylnoradrenaline (alpha -MMA).4 We selected S23515 and S23757, two imidazoline-like drugs with negligible affinities and activities at alpha (2)ARs but with high affinities for non-adrenergic imidazoline binding sites (IBS).5 S23515 decreased BP dose-dependently (-27 +/-5% maximal effect) when administered intracisternally (i.c.) to anaesthetized rabbits. The hypotensioninduced by S23515 (100 mug kg i.c.) was prevented by S23757 (1 mg kg(-1) i.c.) and efaroxan (10 mug kg(-1) i.c.), while these compounds, devoid of haemodynamic action by themselves, did not alter the hypotensive effect of alpha -MNA (3 and 30 mug kg(-1) i.c.). Moreover, the alpha (2)ARs antagonist rauwolscine (3 mug kg(-1) i.c.) did not prevent the effect of S23515.6 Finally, whilst 3 mug kg(-1) of S23515 or 0.5 mug kg(-1) of a-MNA had weak hypotensive effects, the sequential i.c. administration of these two drugs induced a marked hypotension (-23 +/-2%).7 These results indicate that an imidazoline-like drug with no alpha (2)-adrenergic properties lowers BP and interacts synergistically with an alpha (2)ARS agonist.

ASDD Area Sistemi Dipartimentali e Documentali, Università di Bologna, Catalogo delle riviste ed altri periodici
Documento generato il 03/12/20 alle ore 15:53:54