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兔心外膜冠状动脉对乙酰胆碱和肾上腺素能受体激动剂的反应。

Responses of the rabbit epicardial coronary artery to acetylcholine and adrenoceptor agonists.

作者信息

Corr L, Burnstock G, Poole-Wilson P

机构信息

Department of Anatomy and Developmental Biology, University College, London, United Kingdom.

出版信息

Cardiovasc Res. 1991 Mar;25(3):256-62. doi: 10.1093/cvr/25.3.256.

DOI:10.1093/cvr/25.3.256
PMID:1674229
Abstract

STUDY OBJECTIVE

The aim was to identify the role of the endothelium in mediating the responses to acetylcholine in the rabbit coronary artery, and to determine whether alpha or beta adrenergic stimulation may cause relaxation via endothelial receptors in the coronary arteries of this species.

DESIGN

Responses to acetylcholine and adrenoceptor agonists were compared in isolated ring preparations with and without endothelium. The adrenoceptor agonists were examined in the presence of phentolamine or propranolol to block alpha and beta adrenoceptors, respectively.

EXPERIMENTAL MATERIAL

30 New Zealand white rabbits (2.3-3.4 kg) were killed by an overdose of barbiturate and exsanguination, and the left epicardial coronary artery was dissected free. Ring preparations were suspended in organ baths under isometric tension and, where required, the tone of the preparations was raised by KC1.

MEASUREMENTS AND MAIN RESULTS

Concentrations of acetylcholine up to 10(-6) mol.litre-1 produced dose dependent relaxation of the preparations with endothelium intact, but no relaxation in preparations denuded of endothelium. At higher concentrations, a marked vasoconstrictor response was seen in all preparations regardless of the presence of endothelium. At basal tone, acetylcholine produced vasoconstriction which reached a maximum of 1.0 (SEM 0.14)g tension in preparations with endothelium and 1.74(0.27) g tension in those without endothelium (p less than 0.05). In coronary arteries pretreated with 50 mumol.litre-1 phenoxybenzamine to block alpha adrenoceptors, noradrenaline, isoprenaline, and salbutamol produced dose dependent relaxation of the preparations; this was unaffected by the absence of endothelium. In vessels not pretreated with phenoxybenzamine, propranolol inhibited the relaxation to noradrenaline and isoprenaline but again there was no difference between vessels with and without endothelium.

CONCLUSIONS

In the rabbit isolated epicardial coronary artery, acetylcholine produces an endothelium dependent relaxant response over a limited concentration range; a vasoconstrictor response via smooth muscle dominates at higher concentrations. beta Adrenoceptors mediating relaxation are present on the smooth muscle, but there was no evidence for either alpha or beta adrenoceptor mediated responses via the endothelium. Important differences with coronary arteries from other species are discussed.

摘要

研究目的

旨在确定内皮在介导兔冠状动脉对乙酰胆碱反应中的作用,并确定α或β肾上腺素能刺激是否可通过该物种冠状动脉中的内皮受体引起舒张。

设计

比较有内皮和无内皮的离体环行标本对乙酰胆碱和肾上腺素能受体激动剂的反应。在分别存在酚妥拉明或普萘洛尔以阻断α和β肾上腺素能受体的情况下检测肾上腺素能受体激动剂。

实验材料

30只新西兰白兔(体重2.3 - 3.4千克)过量注射巴比妥酸盐并放血处死,游离出左心外膜冠状动脉。将环行标本置于等长张力的器官浴中,必要时用氯化钾升高标本的张力。

测量与主要结果

浓度高达10⁻⁶摩尔/升的乙酰胆碱可使内皮完整的标本产生剂量依赖性舒张,但对去内皮的标本无舒张作用。在较高浓度时,无论有无内皮,所有标本均出现明显的血管收缩反应。在基础张力下,乙酰胆碱在有内皮的标本中产生血管收缩,最大张力达1.0(标准误0.14)克,在无内皮的标本中为1.74(0.27)克(P < 0.05)。在用50微摩尔/升酚苄明预处理以阻断α肾上腺素能受体的冠状动脉中去甲肾上腺素、异丙肾上腺素和沙丁胺醇可使标本产生剂量依赖性舒张;有无内皮对此无影响。在未用酚苄明预处理的血管中,普萘洛尔抑制对去甲肾上腺素和异丙肾上腺素的舒张反应,但有内皮和无内皮的血管之间同样无差异。

结论

在兔离体心外膜冠状动脉中,乙酰胆碱在有限的浓度范围内产生内皮依赖性舒张反应;在较高浓度时,平滑肌介导的血管收缩反应占主导。介导舒张的β肾上腺素能受体存在于平滑肌上,但没有证据表明存在通过内皮的α或β肾上腺素能受体介导的反应。讨论了与其他物种冠状动脉的重要差异。

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