Calcimimetic R568 reduced the blood pressure and improved aortic remodeling in spontaneously hypertensive rats by inhibiting local renin-angiotensin system activity.
Calcimimetic R568 reduced the blood pressure and improved aortic remodeling in spontaneously hypertensive rats by inhibiting local renin-angiotensin system activity.
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拟钙剂 R568 通过抑制局部肾素-血管紧张素系统活性降低自发性高血压大鼠的血压并改善主动脉重塑
DOI：
10.3892/etm.2018.6734
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发表时间：
2018-11
影响因子：
2.7
通讯作者：
He F
中科院分区：
文献类型：
--
作者：
Sun R;Zhang W;Zhong H;Wang L;Tang N;Liu Y;Zhao Y;Zhang T;He F
高血压是严重影响人类健康的心血管疾病。钙敏感受体(CaSR)的激活通过增加[Ca~(2+)]i抑制环磷酸腺苷(CAMP)的形成，进而抑制肾素的释放。肾素-血管紧张素系统(RAS)在原发性高血压(EH)的发生发展中起重要作用。本研究旨在探讨NPSR568(R568)激活的CaSR对自发性高血压大鼠(SHR)血压、血管平滑肌细胞增殖和重构以及RAS活性的影响。在本研究中，我们用R568给SHR和Wistar-京都大鼠治疗8周。采用尾套法每周测量大鼠血压。苏木精-伊红染色和Masson染色观察胸主动脉的形态变化。用Western blotting和免疫组织化学方法检测RAS相关蛋白和增殖性重构蛋白在胸主动脉中的表达。采用双抗体夹心酶联免疫吸附试验检测血浆和胸主动脉cAMP、RAS、CaSR含量。最后，我们发现R568治疗8周降低了SHR的血压，抑制了动脉血管的增殖性重构。R568可显著抑制SHR胸主动脉局部RAS的活性。此外，R568治疗逆转了SHR中CaSR的低表达。R568可作为治疗EH的有效策略。
Hypertension is a cardiovascular disease that seriously affects human health. Activation of the calcium-sensing receptor (CaSR) inhibits cyclic adenosine monophosphate (cAMP) formation by increasing [Ca2+]i and subsequently inhibiting renin release. The renin-angiotensin system (RAS) plays an important role in the development of essential hypertension (EH). The purpose of this study was to determine the effects of NPSR568 (R568)-activated CaSR on blood pressure (BP), proliferation, and remodeling of vascular smooth muscle cells, and the activity of the RAS in spontaneously hypertensive rats (SHRs). In this study, we treated SHR and Wistar-Kyoto rats with R568 for 8 weeks. The tail-cuff method was used to assess rat BP weekly. Morphological changes in the thoracic aorta were evaluated with hematoxylin-eosin and Masson staining. Western blotting and immunohistochemistry were used to detect the expression of RAS-related proteins and proliferative remodeling proteins in the thoracic aorta. An enzyme-linked immunosorbent assay was used to detect the content of cAMP, the RAS, and the CaSR in plasma and the thoracic aorta. Finally, we found that treatment with R568 for 8 weeks reduced the BP and inhibited arterial vascular proliferation remodeling in SHRs. R568 administration significantly suppressed the activity of local RAS in the thoracic aortas of SHRs. Moreover, R568 treatment reversed the low expression of CaSR in SHRs. R568 may serve as an effective strategy against EH.
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影响因子：
9.8
作者：
AYACHI, S
通讯作者：
AYACHI, S
DOI：
10.1152/ajpregu.00238.2010
发表时间：
2010-10-01
影响因子：
2.8
作者：
Atchison, Douglas K.;Ortiz-Capisano, Cecilia;Beierwaltes, William H.
通讯作者：
Beierwaltes, William H.
DOI：
10.1152/ajprenal.00474.2006
发表时间：
2007-09-01
影响因子：
4.2
作者：
Molostvov, Guerman;James, Sean;Zehnder, Daniel
通讯作者：
Zehnder, Daniel
影响因子：
5.6
作者：
Osborn, Jobn W.;Fink, Gregory D.;Raizada, Moban K.
通讯作者：
Raizada, Moban K.
影响因子：
3
作者：
Nakagawa, Kumiko;Parekh, Niru;Schmitt, Claus Peter
通讯作者：
Schmitt, Claus Peter