{'fraction_non_alphanumeric': 0.040798226164079826, 'fraction_numerical': 0.03725055432372506, 'mean_word_length': 6.230769230769231, 'pattern_counts': {'":': 0, '<': 0, '<?xml version=': 0, '>': 0, 'https://': 0, 'lorem ipsum': 0, 'www.': 0, 'xml': 0}, 'pii_count': 0, 'substrings_counts': 0, 'word_list_counts': {'cursed_substrings.json': 0, 'profanity_word_list.json': 0, 'sexual_word_list.json': 0, 'zh_pornsignals.json': 0}}
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, NG‐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 (≤1 × 10−6 m). Clonidine and UK 14304 induced only contractions on endothelium‐intact and endothelium‐denuded aortic rings contracted with prostaglandin F2α (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 α1D‐AR selective antagonist, BMY 7378, and rauwolscine. The pA2 and pKB values for BMY 7378 and rauwolscine, respectively, against endothelium‐independent actions of clonidine and UK 14304 were characteristic of an effect on the α1D‐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.