AT₁ angiotensin II receptor and novel non-AT₁, non-AT₂ angiotensin II/III binding site in brainstem cardiovascular regulatory centers of the spontaneously hypertensive rat.
AT₁ angiotensin II receptor and novel non-AT₁, non-AT₂ angiotensin II/III binding site in brainstem cardiovascular regulatory centers of the spontaneously hypertensive rat.
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DOI：
10.1016/j.brainres.2010.08.081
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发表时间：
2010-11-04
期刊：
影响因子：
2.9
通讯作者：
Speth RC
中科院分区：
文献类型：
--
作者：
Bourassa EA;Fang X;Li X;Sved AF;Speth RC
自发性高血压大鼠（SHR）有一个激活的脑血管紧张素系统，在这个动物模型中有助于血压升高。生理和药理学研究表明，脑AT1血管紧张素受体的过度激活是一个主要的病理生理因素。与这些观察结果一致，放射性配体结合研究表明SHR中脑血管紧张素受体广泛上调。AT1受体刺激导致SHR患者血压升高的一个关键脑干部位是延髓吻侧腹侧（RVLM）。然而，没有定量比较SHR和正常血压大鼠RVLM中AT1受体的结合情况。最近在大脑中发现了一种新的，非at1，非at2结合位点，专门针对血管紧张素II和III。为了确定放射配体与AT1受体或这种新型血管紧张素结合位点的结合是否在RVLM和SHR的其他尾侧脑干区域发生改变，我们对SHR与正常血压Wistar-Kyoto大鼠的放射配体结合进行了定量密度自放射成像比较。在RVLM和尾侧腹外侧延髓（CVLM）以及背内侧延髓（DMM）中，SHR中AT1受体结合的表达增加（分别为13.9%和23%）。相反，在SHR的RVLM和DMM中，新的、非at1、非at2、血管紧张素II和III结合位点的表达减少（分别为37%和13%）。RVLM中AT1受体结合的增加可能导致SHR高血压。SHR RVLM中新的非at1、非at2血管紧张素结合位点的放射性配体结合减少，可能表明该结合位点通过与血管紧张素II和III的相互作用降低血压。
Spontaneously hypertensive rats (SHR) have an activated brain angiotensin system that contributes to the elevation of blood pressure in this animal model. Physiological and pharmacological studies suggest that hyperactivation of brain AT1 angiotensin receptors is a major pathophysiological factor. Consistent with these observations, radioligand binding studies indicate widespread up-regulation of brain angiotensin receptors in SHR. One key brainstem site in which AT1 receptor stimulation appears to contribute to the elevated blood pressure in SHR is the rostral ventrolateral medulla (RVLM). However, no quantitative comparison of AT1 receptor binding in the RVLM has been made in SHR versus normotensive rats. A novel, non-AT1, non-AT2 binding site, specific for angiotensins II and III has recently been discovered in the brain. To determine if radioligand binding to either AT1 receptors or this novel angiotensin binding site are altered in the RVLM and other caudal brainstem regions of SHR, a quantitative densitometric autoradiographic comparsion of radioligand binding in SHR versus normotensive Wistar-Kyoto rats was made. In both the RVLM and caudal ventrolateral medulla (CVLM) as well as dorsomedial medulla (DMM), there was increased expression of AT1 receptor binding in SHR (13, 9 and 23%, respectively). Conversely, expression of the novel, non-AT1, non-AT2, angiotensin II and III binding site was decreased in the RVLM and DMM of SHR (37 and 13%, respectively). This increased AT1 receptor binding in the RVLM may contribute to the hypertension of SHR. Reduced radioligand binding to the novel, non-AT1, non-AT2, angiotensin binding site in the RVLM of SHR may indicate a role for this binding site to reduce blood pressure via its interactions with angiotensins II and III.
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影响因子：
3.7
作者：
Karamyan, Vardan T.;Arsenault, Jason;Escher, Emanuel;Speth, Robert C.
通讯作者：
Speth, Robert C.
DOI：
10.1152/ajpregu.00852.2004
发表时间：
2006-04-01
影响因子：
2.8
作者：
Alzamora, AC;Santos, RAS;Campagnole-Santos, MJ
通讯作者：
Campagnole-Santos, MJ
影响因子：
3.1
作者：
Barone, Frank C.;Willette, Robert N.;Coatney, Robert W.
通讯作者：
Coatney, Robert W.
影响因子：
--
作者：
FOW, JE;AVERILL, DB;BARNES, KL
通讯作者：
BARNES, KL
影响因子：
13.5
作者：
Jones ES;Vinh A;McCarthy CA;Gaspari TA;Widdop RE
通讯作者：
Widdop RE