Role of angiotensin II receptor subtypes in porcine basilar artery: Functional, radioligand binding, and cell culture studies

Role of angiotensin II receptor subtypes in porcine basilar artery: Functional, radioligand binding, and cell culture studies
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DOI:
10.1016/j.lfs.2005.06.044
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发表时间:
2006-01-25
期刊:
影响因子:
6.1
通讯作者:
Nishio, A
Nishio, A
中科院分区:
医学2区
文献类型:
--
作者:
Miyamoto, A;Wada, R;Nishio, A

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我们的目的是澄清响应血管紧张素(Ang)II在猪基底动脉和An II受体亚型的作用,功能,放射性配体结合,和细胞培养研究。血管紧张素II诱导更有力的收缩在近端部分比在远端部分的离体猪基底动脉。Ang II引起的收缩可被An II 1型(AT(1))受体拮抗剂洛沙坦抑制,而Ang II 2型(AT(2))受体拮抗剂PD 123319增强,去除内皮后,洛沙坦的作用仍然存在,但PD 123319的作用被取消。[H-3]Ang II在平滑肌膜上的特异性结合位点被氯沙坦抑制,但不被PD 123319抑制。刺激血管紧张素II增加一氧化氮(NO)的产生在培养的基底动脉内皮细胞。PD 123319和NO合酶抑制剂L-N-G-硝基精氨酸可抑制这种合成。结果提示,Ang Ⅱ引起的血管收缩可能通过激活基底动脉平滑肌细胞上的AT(1)受体介导,并通过激活内皮细胞上的AT(1)受体调节NO的产生。(c)2005年爱思唯尔公司All rights reserved.
We aimed to clarify responsiveness to angiotensin (Ang) II in the porcine basilar artery and the role of An II receptor subtypes by functional, radioligand binding, and cell culture studies. Ang II induced more potent contractions in the proximal part than in the distal part of isolated porcine basilar arteries. The contraction induced by Ang II was inhibited by the An II type 1 (AT(1)) receptor antagonist losartan, but the Ang II type 2 (AT(2)) receptor antagonist PD123319 enhanced it. After removal of the endothelium, the effect of losartan remained but the effect of PD123319 was abolished. The specific binding site of [H-3]Ang II on the smooth muscle membrane was inhibited by losartan, but not by PD123319. Stimulation of angiotensin II increased nitric oxide (NO) production in cultured basilar arterial endothelial cells. This production was inhibited by PD123319 and the NO synthase inhibitor L-N-G-nitroarginine. These results suggest that the contraction induced by Ang II might be mediated via the activation of AT(1) receptors on the basilar arterial smooth muscle cells and be modulated via the activation of AT(1) receptors on the endothelial cells, followed by NO production. (c) 2005 Elsevier Inc. All rights reserved.