Interplay between brain stem angiotensins and monocyte chemoattractant protein-1 as a novel mechanism for pressor response after ischemic stroke

被引：14

作者：

Chang, Alice Y. W. ^{[1
,2
,3
,4
]}

Li, Faith C. H. ^{[1
]}

Huang, Chi-Wei ^{[4
,5
]}

Wu, Julie C. C. ^{[1
]}

Dai, Kuang-Yu ^{[1
]}

Chen, Chang-Han ^{[1
]}

Li, Shau-Hsuan ^{[6
]}

Su, Chia-Hao ^{[1
]}

Wu, Re-Wen ^{[7
]}

机构：

[1] Kaohsiung Chang Gung Mem Hosp, Ctr Translat Res Biomed Sci, Kaohsiung, Taiwan

[2] Natl Cheng Kung Univ, Dept Physiol, Tainan 70101, Taiwan

[3] Kaohsiung Med Univ, Dept Pharmacol, Kaohsiung, Taiwan

[4] Natl Sun Yat Sen Univ, Dept Biol Sci, Kaohsiung 80424, Taiwan

[5] Kaohsiung Chang Gung Mem Hosp, Dept Neurol, Kaohsiung, Taiwan

[6] Kaohsiung Chang Gung Mem Hosp, Dept Hematol & Oncol, Kaohsiung, Taiwan

[7] Kaohsiung Chang Gung Mem Hosp, Dept Orthoped, Kaohsiung, Taiwan

来源：

NEUROBIOLOGY OF DISEASE | 2014年 / 71卷

关键词：

Ischemic stroke; Middle cerebral artery occlusion; Pressor response after stroke; Angiotensin isoforms and receptors; Monocyte chemoattractant protein-1; Neuroinflammation; Aliskiren; Rostral ventrolateral medulla; ROSTRAL VENTROLATERAL MEDULLA; CEREBRAL-ARTERY OCCLUSION; BLOOD-PRESSURE; UP-REGULATION; RECEPTOR; HYPERTENSION; INHIBITION; EXPRESSION; ALISKIREN; DAMAGE;

D O I：

10.1016/j.nbd.2014.08.005

中图分类号：

Q189 [神经科学];

学科分类号：

071006 [神经生物学];

摘要：

Pressor response after stroke commonly leads to early death or susceptibility to stroke recurrence, and detailed mechanisms are still lacking. We assessed the hypothesis that the renin-angiotensin system contributes to pressor response after stroke by differential modulation of the pro-inflammatory chemokine monocyte chemoattractant protein-1 (MCP-1) in the rostral ventrolateral medulla (RVLM), a key brain stem site that maintains blood pressure. We also investigated the beneficial effects of a novel renin inhibitor, aliskiren, against stroke-elicited pressor response. Experiments were performed in male adult Sprague-Dawley rats. Stroke induced by middle cerebral artery occlusion elicited significant pressor response, accompanied by activation of angiotensin II (Ang II)/type I receptor (AT1R) and AT2R signaling, depression of Ang-(1-7)/MasR and Ang IV/AT4R cascade, alongside augmentation of MCP-1/C-C chemokine receptor 2 (CCR2) signaling and neuroinflammation in the RVLM. Stroke-elicited pressor response was significantly blunted by antagonism of AT1R, AT2R or MCP-1/CCR2 signaling, and eliminated by applying Ang-(1-7) or Ang IV into the RVLM. Furthermore, stroke-activated MCP-1/CCR2 signaling was enhanced by AT1R and AT2R activation, and depressed by Ang-(1-7)/MasR and Ang IV/AT4R cascade. Aliskiren inhibited stroke-elicited pressor response via downregulating MCP-1/CCR2 activity and reduced neuroinflammation in the RVLM; these effects were potentiated by Ang-(1-7) or Ang IV. We conclude that whereas Ang II/AT1R or Ang II/AT2R signaling in the brain stem enhances, Ang-(1-7)/MasR or Ang IV/AT4R antagonizes pressor response after stroke by differential modulations of MCP-1 in the RVLM. Furthermore, combined administration of aliskiren and Ang-(1-7) or Ang IV into the brain stem provides more effective amelioration of stroked-induced pressor response. (C) 2014 Elsevier Inc. All rights reserved.

引用

页码：292 / 304

页数：13

共 51 条

[41]

Tissue factor and monocyte chemoattractant protein-1 expression in hypertensive individuals with normal or increased carotid intima-media wall thickness [J].