在高血压和衰老期间,去除外膜不会改变主动脉α 1d -肾上腺素受体的反应

J. H. Gómez-Zamudio, R. Villalobos-Molina
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引用次数: 1

摘要

1本研究的目的是表征α1-肾上腺素能受体(α1-ARs)在离体主动脉中膜、正常血压Wistar Kyoto (WKY)和自发性高血压(SHR)大鼠(1、3、6和12月龄大鼠)衰老和高血压过程中存在的特征。在所有血管中,内皮被去除。在分离的主动脉环中,苯肾上腺素以浓度和年龄依赖的方式增加收缩,与WKY大鼠相比,老年SHR大鼠的收缩功能受损。α1-AR选择性拮抗剂prazosin在两大鼠血管中均表现出高亲和力(pA2)。4 α1A-AR选择性拮抗剂RS 100329(5-甲基-3-[3-[4-[2-(2,2,2,-三氟乙氧基)苯基]-1-哌嗪基]丙基]-2,4-(1H)-嘧啶二酮)和5-甲基乌拉地尔拮抗主动脉苯肾上腺素反应的效价较低。α1D-AR选择性拮抗剂BMY 7378(8-[2-[4-(2-甲氧基苯基)-1哌嗪基]乙基]-8-阿兹匹斯罗[4.5]十二烷-7,9-二酮)在两种菌株和所有年龄的主动脉中都能有效阻断苯肾上腺素诱导的反应。6去除外膜可降低老年大鼠的Emax并改变其相对亲和力(pD2),但不影响选择性拮抗剂的亲和力。7结果提示,在肾上腺素诱导的大鼠主动脉收缩中,主动脉α1D-AR是主要亚型,α1A-AR仅起次要作用。8衰老和高血压并没有改变血管中的α1-ARs,即使α1-ARs表达,外膜似乎也不参与收缩。
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Adventitia removal does not modify the α1D-adrenoceptors response in aorta during hypertension and ageing

1 The aim of the current study was to characterize the α1-adrenergic receptors (α1-ARs) present in the isolated tunica media of aorta, in normotensive Wistar Kyoto (WKY) and spontaneously hypertensive (SHR) rats during the course of ageing and hypertension (rats of 1, 3, 6 and 12 months of age). In all vessels, endothelium was removed.

2 In isolated aortic rings, phenylephrine increased contraction in a concentration- and age-dependent manner and was impaired in old SHR compared with WKY rats.

3 The α1-AR selective antagonist prazosin showed high affinity (pA2) in vessels from both rat strains.

4 The potency of the α1A-AR selective antagonists, RS 100329 (5-methyl-3-[3-[4-[2-(2,2,2,-trifluoroethoxy) phenyl]-1-piperazinyl] propyl]-2,4-(1H)-pyrimidinedione) and 5-methylurapidil in antagonizing aortic phenylephrine-responses was low.

5 The α1D-AR selective antagonist, BMY 7378 (8-[2-[4-(2-methoxyphenyl)-1 piperazynil] ethyl]-8-azaspiro [4.5] decane-7,9-dione) potently blocked phenylephrine-induced responses in aorta from both strains and at all ages.

6 Adventitia removal decreased Emax in older rats and modified the relative affinity (pD2), but did not affect the affinity of the selective antagonists.

7 The results suggest that aorta tunica α1D-AR is the main subtype involved in phenylephrine-induced contraction of rat aorta, while α1A-AR plays only a minor role.

8 Ageing and hypertension did not modify α1-ARs in the blood vessel and the tunica adventitia does not seem to participate in contraction, even though α1-ARs are expressed.

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Issue Information Autonomic and Autacoid Pharmacology: Goodbye and thank you Attenuation of the anti-contractile effect of cooling in the rat aorta by perivascular adipose tissue Retraction: Dopamine receptor immunohistochemistry in the rat choroid plexus. Issue Information
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