Evidence against α₂-adrenoceptors mediating relaxation in rat thoracic aortae: α₂-agonists relaxation depends on interaction with α₁-adrenoceptors

In rat aorta, the presence of functional α₂-adrenoceptors (α₂-AR) was investigated in ring preparations preconstricted with α₁-adrenergic and non- α₁-adrenergic agonists. Particularly, the hypothetical interference of α₂-AR agonists with α₁-AR-mediated vasoconstriction was evaluated. Relaxant and contractile responses to α₂-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 EC₅₀) 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 α₂-AR antagonist, rauwolscine (≤ × 10^-6 M). Clonidine and UK 14304 induced only contractions on endothelium-intact and endothelium-denuded aortic rings contracted with prostaglandin F _2α (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 pA₂ and pK_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 α₂-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 α₂-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 α₁-AR), inhibitory and excitatory, interaction with α₁-ARs.