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

Abstract

In rat aorta, the presence of functional alpha(2)-adrenoceptors (alpha(2)-AR) was investigated in ring preparations preconstricted with alpha(1)-adrenergic and non- alpha(1)-adrenergic agonists. Particularly, the hypothetical interference of alpha(2)-AR agonists with alpha(1)-AR-mediated vasoconstriction was evaluated. Relaxant and contractile responses to alpha(2)-AR agonists were obtained. In endothelium-intact and endothelium-denuded aortic rings preconstricted with phenylephrine (1 x 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 alpha(2)-AR antagonist, rauwolscine (< or =1 x 10(-6) m). Clonidine and UK 14304 induced only contractions on endothelium-intact and endothelium-denuded aortic rings contracted with prostaglandin F(2alpha) (3 x 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 alpha(1D)-AR selective antagonist, BMY 7378, and rauwolscine. The pA(2) 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 alpha(1D)-AR. The other selective alpha(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 alpha(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 alpha(1)-AR), inhibitory and excitatory, interaction with alpha(1)-ARs.

Effect of 17β‐oestradiol replacement on vascular responsiveness in ovariectomized diabetic rats

“…Both inhibitors were added to the organ baths at the time when the medium was switch to CFM. In a second series of experiments, used to evaluate the mechanism underlying the PE (10 )6 mol ⁄ L)-induced contractile responses in the absence and presence of N G -nitro-L-arginine methyl ester (L-NAME; 10 )6 mol ⁄ L, 30 min), 12 superoxide dismutase (SOD; 100 U ⁄ mL, 15 min) 13 and indomethacin (10 )6 mol ⁄ L, 15 min, aortic segments were incubated with the inhibitors prior to the evaluation of PE-induced vasoconstrictor responses. 14…”

Acute intravenous injection and short‐term oral administration of NG‐nitro‐l‐arginine methyl ester to the rat provoke increased pressor responses to agonists and hypertension, but not inhibition of acetylcholine‐induced hypotensive responses

“…Finally, l ‐NAME treatments did not significantly enhanced phenylephrine‐induced contractions in isolated aortic tissues, as could be expected as basal endothelial NO release may attenuate constrictor responses in rat aorta [29,30]. Nevertheless, the failure to obtain an increase in agonist‐induced constriction after endothelium removal in rat aorta has already been reported [31,32].…”

Adrenergic Modulation With Photochromic Ligands

“…Besides being generally recognized as a potent central hypotensive agent, [27] clonidine is also known to induce vasodilation by acting directly on vascular adrenoceptors [25] . This peripheral response involves stimulation of endothelial α 2 ‐ARs as well as partial agonism towards α 1 ‐ARs of the vascular smooth muscle, and results in relaxation of endothelium‐intact strips previously contracted with phenylephrine (PE) [26, 28–30] . When testing if our analogues displayed a similar behaviour, we observed that exposure to UV light alone could induce relaxation of the vascular smooth muscle, substantially abolishing the contraction evoked by PE [31] .…”