High-Salt Diet Inhibits Expression of Angiotensin Type 2 Receptor in Resistance Arteries
High-Salt Diet Inhibits Expression of Angiotensin Type 2 Receptor in Resistance Arteries
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高盐饮食抑制阻力动脉中2型血管紧张素受体的表达
DOI：
10.1161/01.hyp.0000161990.98383.ad
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发表时间：
2005
期刊：
影响因子：
8.3
通讯作者：
L. Michea
中科院分区：
文献类型：
--
作者：
Magdalena González;L. Lobos;F. Castillo;L. Galleguillos;Nandy C Lopez;L. Michea
近年来的研究表明，2型血管紧张素受体（AT 2 R）可能参与调节血压和/或血管重塑。一个关键问题涉及血管AT 2 R表达的潜在调节剂的作用。在本研究中，我们评估了高盐摄入（70 mmol/L NaCl饮用水）是否可以调节大鼠肠系膜动脉AT 2 R功能和表达。在大鼠小直径动脉加压灌注中，研究了血管紧张素Ⅱ（AT 1 R）拮抗剂氯沙坦（Losartan）的量效曲线。用苯乙哌啶预收缩动脉，使静息直径减少约30%。血管紧张素剂量依赖性地舒张预收缩动脉，激活AT 2 R（为苯肾上腺素收缩的60.1±9.1%，P<0.05）。与此相反，AT 2 R依赖性舒张没有观察到从高盐饮食大鼠的动脉。半定量逆转录聚合酶链反应（RT-PCR）结果显示，高盐饮食组大鼠动脉AT 2 RmRNA表达量较对照组减少（65.5±7.5%，P<0.05）。Westernblot结果显示高盐饮食大鼠肠系膜动脉蛋白组分中AT 2 R降低（60.0±18.0，P<0.05）。在第二组实验中，肾上腺切除（4天）减弱了AT 2 R介导的血管舒张作用，并降低了AT 2 R mRNA（为对照水平的72.0±11.0%，P<0.05）。ADX组大鼠肠系膜动脉蛋白组分中AT 2 R的丰度也明显降低（64.0±13%）（P<0.05）。盐皮质激素替代治疗可阻止AT 2 R mRNA和蛋白的下调。最后，生理浓度的醛固酮引起小直径肠系膜动脉外植体的AT 2 R mRNA的剂量依赖性增加。结果与醛固酮介导的AT 2 R上调一致。
Recent studies suggested that type 2 angiotensin receptor (AT2R) could contribute to regulation of blood pressure and/or vascular remodeling. A key question relates to the effects of potential modulators of vascular AT2R expression. In the present work, we evaluated if high salt intake (70 mmol/L NaCl in drinking water) could modulate rat mesenteric artery AT2R function and expression. Angiotensin II dose-response curves were studied in rat perfused pressurized small-diameter arteries in the presence of losartan (AT1R antagonist). Arteries were precontracted with phenylephrine, yielding ≈30% decrease in resting diameter. AT2R activation by angiotensin-induced dose-dependent relaxation of precontracted arteries (60.1±9.1% of phenylephrine-induced contraction, P<0.05). In contrast, AT2R-dependent relaxation was not observed in arteries obtained from rats on high-salt diet. Semi-quantitative reverse-transcription polymerase chain reaction experiments demonstrated reduced amount of AT2R mRNA in arteries of rats on high-salt diet (65.5±7.5% of control levels, P<0.05). Western blot studies demonstrated decreased AT2R in mesenteric artery protein fractions of high-salt diet rats (60.0±18.0 of control levels, P<0.05). In a second set of experiments, adrenalectomy (4 days) blunted AT2R-mediated vasorelaxation and decreased AT2R mRNA (72.0±11.0% of control levels, P<0.05). AT2R abundance in protein fractions of mesenteric arteries of ADX rats was also diminished (64.0±13% of control levels, P<0.05). Both, AT2R mRNA and protein downregulation were prevented by mineralocorticoid replacement therapy. Finally, physiological concentrations of aldosterone caused a dose-dependent increase in AT2R mRNA of small diameter mesenteric artery explants. The results are consistent with aldosterone-mediated upregulation AT2R.
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DOI：
10.1172/jci6063
发表时间：
1999
期刊：
The Journal of clinical investigation
影响因子：
--
作者：
Siragy,HM;Senbonmatsu,T;Ichiki,T;Inagami,T;Carey,RM
通讯作者：
Carey,RM
DOI：
10.1172/jci119531
发表时间：
1997-07
期刊：
The Journal of clinical investigation
影响因子：
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作者：
H. Siragy;Robert M. Carey
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H. Siragy;Robert M. Carey
长期低剂量输注血管紧张素 II 和醛固酮对大鼠平滑肌和肾上腺血管紧张素 II 受体的影响。
影响因子：
4.8
作者：
Douglas,JG;Brown,GP
通讯作者：
Brown,GP
人类 2 型血管紧张素 II 受体的序列和基因组结构。
DOI：
10.1006/bbrc.1995.1537
发表时间：
1995
期刊：
Biochemical and biophysical research communications.
影响因子：
--
作者：
Martin,MM;Elton,TS
通讯作者：
Elton,TS
DOI：
10.1073/pnas.92.23.10663
发表时间：
1995-11-07
影响因子：
11.1
作者：
NAKAJIMA, M;HUTCHINSON, HG;DZAU, VJ
通讯作者：
DZAU, VJ