Beta 3‐adrenoceptor stimulation induces vasorelaxation mediated essentially by endothelium‐derived nitric oxide in rat thoracic aorta

Beta 3‐adrenoceptor stimulation induces vasorelaxation mediated essentially by endothelium‐derived nitric oxide in rat thoracic aorta
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β3-肾上腺素受体刺激诱导大鼠胸主动脉内皮源性一氧化氮介导的血管舒张

DOI:
10.1038/sj.bjp.0702797
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发表时间:
1999
影响因子:
7.3
通讯作者:
C. Gauthier
C. Gauthier
中科院分区:
医学2区
文献类型:
--
作者:
J. Trochu;V. Leblais;Y. Rautureau;F. Bévérelli;H. Le Marec;A. Berdeaux;C. Gauthier

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异丙肾上腺素的舒张作用可能是由于除β1和β2外的另一种β-肾上腺素受体亚型的激活所致。本研究评价了第三种β肾上腺素受体亚型β3在异丙肾上腺素诱导的大鼠胸主动脉舒张中的作用。异丙肾上腺素对苯肾上腺素预收缩的胸主动脉环产生浓度依赖性舒张(pD 2 =7.46±0.15; Emax=85.9±3.4%),内皮去除(Emax=66.5±6.3%)和一氧化氮(NO)合酶抑制剂L-NG-单甲基精氨酸(L-NMMA)给药(Emax=61.3±7.9%)可部分减弱。在存在纳多洛尔(一种β1-和β2-肾上腺素受体拮抗剂)的情况下,异丙肾上腺素诱导的舒张持续存在(Emax=55.6±5.3%),但与不存在纳多洛尔的情况相比,在更高的浓度下(pD 2 =6.71±0.10)发生,持续时间更长。两种β3-肾上腺素受体激动剂获得了相似的舒张作用:SR 58611(一种优先β3-肾上腺素受体激动剂)和CGP 12177(一种具有β1-和β2-肾上腺素受体拮抗特性的部分β3-肾上腺素受体)。SR 58611引起浓度依赖性舒张(pD 2 =5.24±0.07; Emax=59.5±3.7%),纳多洛尔预处理未改变该效应,但SR 59230 A(一种β3-肾上腺素受体拮抗剂)可拮抗该效应。SR 58611诱导的舒张与组织环GMP含量增加1.7倍相关。内皮去除和存在L-NMMA的情况下,SR 58611诱导的舒张和环GMP增加均大幅降低。我们的结论是,在大鼠胸主动脉中,β3-肾上腺素受体主要位于内皮细胞上,并与β1-和β2-肾上腺素受体协同作用,通过激活NO合酶途径介导舒张,随后增加环GMP水平。
The relaxant effects of isoprenaline may result from activation of another β‐adrenoceptor subtype in addition to β1 and β2. This study evaluated the role of a third β‐adrenoceptor subtype, β3, in β‐adrenoceptor‐induced relaxation of rat thoracic aorta by isoprenaline. Isoprenaline produced a concentration‐dependent relaxation of phenylephrine pre‐contracted rings of the thoracic aorta (pD2=7.46±0.15; Emax=85.9±3.4%), which was partially attenuated by endothelium removal (Emax=66.5±6.3%) and administration of the nitric oxide (NO) synthase inhibitor, L‐NG‐monomethyl arginine (L‐NMMA) (Emax=61.3±7.9%). In the presence of nadolol, a β1‐ and β2‐adrenoceptor antagonist, isoprenaline‐induced relaxation persisted (Emax=55.6±5.3%), but occurred at higher concentrations (pD2=6.71±0.10) than in the absence of nadolol and lasted longer. Similar relaxant effects were obtained with two β3‐adrenoceptor agonists: SR 58611 (a preferential β3‐adrenoceptor agonist), and CGP 12177 (a partial β3‐adrenoceptor with β1‐ and β2‐adrenoceptor antagonistic properties). SR 58611 caused concentration‐dependent relaxation (pD2=5.24±0.07; Emax=59.5±3.7%), which was not modified by pre‐treatment with nadolol but antagonized by SR 59230A, a β3‐adrenoceptor antagonist. The relaxation induced by SR 58611 was associated with a 1.7 fold increase in tissue cyclic GMP content. Both relaxation and the cyclic GMP increase induced by SR 58611 were greatly reduced by endothelium removal and in the presence of L‐NMMA. We conclude that in the rat thoracic aorta, β3‐adrenoceptors are mainly located on endothelial cells, and act in conjuction with β1‐ and β2‐adrenoceptors to mediate relaxation through activation of an NO synthase pathway and subsequent increase in cyclic GMP levels.
DOI: 10.1073/pnas.90.8.3665
发表时间: 1993-04-15
影响因子: 11.1
作者:
LIGGETT, SB;FREEDMAN, NJ;LEFKOWITZ, RJ
通讯作者: LEFKOWITZ, RJ
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DOI: --
发表时间: 1996
期刊: The Journal of pharmacology and experimental therapeutics
影响因子: --
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Shen,YT;Cervoni,P;Claus,T;Vatner,SF
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DOI: --
发表时间: 1994
期刊: The Journal of pharmacology and experimental therapeutics
影响因子: --
作者:
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对异丙肾上腺素的反应与α-和β-肾上腺素受体激动无关。
DOI: 10.1111/j.1476-5381.1987.tb11262.x
发表时间: 1987
影响因子: 7.3
作者:
Bond,RA;Clarke,DE
通讯作者: Clarke,DE
激动剂暴露对分离脂肪细胞中 β1 和 β3 肾上腺素受体与腺苷酸环化酶偶联的影响。
DOI: --
发表时间: 1992
期刊: The Journal of pharmacology and experimental therapeutics
影响因子: --
作者:
Granneman,JG
通讯作者: Granneman,JG