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

Alice Y.W. Chang; Faith C.H. Li; Chi-Wei Huang; Julie C.C. Wu; Kuang-Yu Dai; Chang-Han Chen; Shau-Hsuan Li; Chia-Hao Su; Re-Wen Wu

Neurobiology of Disease (Nov 2014)

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

Alice Y.W. Chang,
Faith C.H. Li,
Chi-Wei Huang,
Julie C.C. Wu,
Kuang-Yu Dai,
Chang-Han Chen,
Shau-Hsuan Li,
Chia-Hao Su,
Re-Wen Wu

Affiliations

Alice Y.W. Chang: Center for Translational Research in Biomedical Sciences, Kaohsiung Chang Gung Memorial Hospital, Kaohsiung, Taiwan, ROC; Department of Physiology, National Cheng Kung University, Tainan, Taiwan, ROC; Department of Pharmacology, Kaohsiung Medical University, Kaohsiung, Taiwan, ROC; Department of Biological Science, National Sun Yat-sen University, Kaohsiung, Taiwan, ROC; Corresponding author at: Center for Translational Research in Biomedical Sciences, Kaohsiung Chang Gung Memorial Hospital, Kaohsiung 833, Taiwan, ROC. Fax: +886 7 7317123x8569.
Faith C.H. Li: Center for Translational Research in Biomedical Sciences, Kaohsiung Chang Gung Memorial Hospital, Kaohsiung, Taiwan, ROC
Chi-Wei Huang: Department of Biological Science, National Sun Yat-sen University, Kaohsiung, Taiwan, ROC; Department of Neurology, Kaohsiung Chang Gung Memorial Hospital, Kaohsiung, Taiwan, ROC
Julie C.C. Wu: Center for Translational Research in Biomedical Sciences, Kaohsiung Chang Gung Memorial Hospital, Kaohsiung, Taiwan, ROC
Kuang-Yu Dai: Center for Translational Research in Biomedical Sciences, Kaohsiung Chang Gung Memorial Hospital, Kaohsiung, Taiwan, ROC
Chang-Han Chen: Center for Translational Research in Biomedical Sciences, Kaohsiung Chang Gung Memorial Hospital, Kaohsiung, Taiwan, ROC
Shau-Hsuan Li: Department of Hematology and Oncology, Kaohsiung Chang Gung Memorial Hospital, Kaohsiung, Taiwan, ROC
Chia-Hao Su: Center for Translational Research in Biomedical Sciences, Kaohsiung Chang Gung Memorial Hospital, Kaohsiung, Taiwan, ROC
Re-Wen Wu: Department of Orthopedics, Kaohsiung Chang Gung Memorial Hospital, Kaohsiung, Taiwan, ROC

Journal volume & issue: Vol. 71
pp. 292 – 304

Abstract

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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.

Published in Neurobiology of Disease

ISSN: 0969-9961 (Print); 1095-953X (Online)
Publisher: Elsevier
Country of publisher: United States
LCC subjects: Medicine: Internal medicine: Neurosciences. Biological psychiatry. Neuropsychiatry
Website: https://www.journals.elsevier.com/neurobiology-of-disease

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