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Evidence against α 2 ‐adrenoceptors mediating relaxation in rat thoracic aortae: α 2 ‐agonists relaxation depends on interaction with α 1 ‐adrenoceptors
Author(s) -
Castillo Enrique F.,
Ortíz Cindy S.,
López Ruth M.,
Ruíz Antonio,
Vélez Juan M.,
Castillo Carlos
Publication year - 2006
Publication title -
fundamental and clinical pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.655
H-Index - 73
eISSN - 1472-8206
pISSN - 0767-3981
DOI - 10.1111/j.1472-8206.2006.00421.x
Subject(s) - rauwolscine , prazosin , chemistry , clonidine , yohimbine , phenylephrine , vasoconstriction , agonist , endothelium , medicine , endocrinology , antagonist , receptor , biochemistry , blood pressure
In rat aorta, the presence of functional α 2 ‐adrenoceptors ( α 2 ‐AR) was investigated in ring preparations preconstricted with α 1 ‐adrenergic and non‐ α 1 ‐adrenergic agonists. Particularly, the hypothetical interference of α 2 ‐AR agonists with α 1 ‐AR‐mediated vasoconstriction was evaluated. Relaxant and contractile responses to α 2 ‐AR agonists were obtained. In endothelium‐intact and endothelium‐denuded aortic rings preconstricted with phenylephrine (1 × 10 −6 m ), the imidazoline derivatives, clonidine and UK14304, induced relaxations with similar order of potencies (−log EC 50 ) and maxima relaxant effects respectively. Pretreatment with the NO synthase inhibitor, N G ‐nitro‐ l ‐arginine methyl ester ( l ‐NAME) had no effect on the relaxant responses to clonidine and UK14304. In phenylephrine‐constricted rings with endothelium, relaxations to clonidine and UK 14304 were not antagonized by the selective α 2 ‐AR antagonist, rauwolscine (≤1 × 10 −6 m ). Clonidine and UK 14304 induced only contractions on endothelium‐intact and endothelium‐denuded aortic rings contracted with prostaglandin F 2 α (3 × 10 −7 m ). Moreover, clonidine and UK 14304‐induced relaxation of endothelium‐denuded arteries precontracted with methoxamine but not with serotonin. Finally, the concentration–contraction curves to clonidine and UK 14304 in endothelium‐denuded aortic rings were significantly shifted to the right by the α 1D ‐AR selective antagonist, BMY 7378, and rauwolscine. The p A 2 and p K B values for BMY 7378 and rauwolscine, respectively, against endothelium‐independent actions of clonidine and UK 14304 were characteristic of an effect on the α 1D ‐AR. The other selective α 2 ‐AR agonist tested BHT 933 (an azepine derivative), lacks considerable relaxant and contractile effects in rat aorta. The results provide no evidence for the presence of functional α 2 ‐AR in rat aorta. Respectively, the relaxant and contractile effects of the imidazoline derivatives, clonidine and UK 14304, may be due to an adjustable (in relation to the agonist‐dependent active state of the α 1 ‐AR), inhibitory and excitatory, interaction with α 1 ‐ARs.