Central Renin-Angiotensin System Activation and Inflammation Induced by High-Fat Diet Sensitize Angiotensin II-Elicited Hypertension

Baojian Xue; Robert L Thunhorst; Yang Yu; Fang Guo; Terry G Beltz; Robert B Felder; Alan Kim Johnson

doi:10.1161/HYPERTENSIONAHA.115.06263

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Central Renin-Angiotensin System Activation and Inflammation Induced by High-Fat Diet Sensitize Angiotensin II-Elicited Hypertension

Journal article

Peer reviewed

Central Renin-Angiotensin System Activation and Inflammation Induced by High-Fat Diet Sensitize Angiotensin II-Elicited Hypertension

Baojian Xue, Robert L Thunhorst, Yang Yu, Fang Guo, Terry G Beltz, Robert B Felder and Alan Kim Johnson

Hypertension (Dallas, Tex. 1979), Vol.67(1), pp.163-170

01/2016

DOI: 10.1161/HYPERTENSIONAHA.115.06263

PMCID: PMC4834194

PMID: 26573717

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http://doi.org/10.1161/HYPERTENSIONAHA.115.06263View

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Abstract

Obesity has been shown to promote renin-angiotensin system activity and inflammation in the brain and to be accompanied by increased sympathetic activity and blood pressure. Our previous studies demonstrated that administration of a subpressor dose of angiotensin (Ang) II sensitizes subsequent Ang II-elicited hypertension. The present study tested whether high-fat diet (HFD) feeding also sensitizes the Ang II-elicited hypertensive response and whether HFD-induced sensitization is mediated by an increase in renin-angiotensin system activity and inflammatory mechanisms in the brain. HFD did not increase baseline blood pressure, but enhanced the hypertensive response to Ang II compared with a normal-fat diet. The sensitization produced by the HFD was abolished by concomitant central infusions of either a tumor necrosis factor-α synthesis inhibitor, pentoxifylline, an Ang II type 1 receptor blocker, irbesartan, or an inhibitor of microglial activation, minocycline. Furthermore, central pretreatment with tumor necrosis factor-α mimicked the sensitizing action of a central subpressor dose of Ang II, whereas central pentoxifylline or minocycline abolished this Ang II-induced sensitization. Real-time quantitative reverse transcription-polymerase chain reaction analysis of lamina terminalis tissue indicated that HFD feeding, central tumor necrosis factor-α, or a central subpressor dose of Ang II upregulated mRNA expression of several components of the renin-angiotensin system and proinflammatory cytokines, whereas inhibition of Ang II type 1 receptor and of inflammation reversed these changes. The results suggest that HFD-induced sensitization of Ang II-elicited hypertension is mediated by upregulation of the brain renin-angiotensin system and of central proinflammatory cytokines.

Diet, High-Fat - adverse effects

Rats

Male

Renin-Angiotensin System - physiology

Rats, Sprague-Dawley

Hypertension - physiopathology

Hypertension - etiology

Hypertension - metabolism

Inflammation - metabolism

Animals

Blood Pressure - physiology

Angiotensin II - toxicity

Disease Models, Animal

Details

Title: Subtitle: Central Renin-Angiotensin System Activation and Inflammation Induced by High-Fat Diet Sensitize Angiotensin II-Elicited Hypertension
Creators: Baojian Xue - From the Departments of Psychological and Brain Sciences (B.X., R.L.T., F.G., T.G.B., A.K.J.), Pharmacology (A.K.J.), Internal Medicine (Y.Y., R.B.F.), and the François M. Abboud Cardiovascular Research Center (B.X., R.B.F., A.K.J.), University of Iowa, Iowa City. baojian-xue@uiowa.edu
Robert L Thunhorst - From the Departments of Psychological and Brain Sciences (B.X., R.L.T., F.G., T.G.B., A.K.J.), Pharmacology (A.K.J.), Internal Medicine (Y.Y., R.B.F.), and the François M. Abboud Cardiovascular Research Center (B.X., R.B.F., A.K.J.), University of Iowa, Iowa City
Yang Yu - From the Departments of Psychological and Brain Sciences (B.X., R.L.T., F.G., T.G.B., A.K.J.), Pharmacology (A.K.J.), Internal Medicine (Y.Y., R.B.F.), and the François M. Abboud Cardiovascular Research Center (B.X., R.B.F., A.K.J.), University of Iowa, Iowa City
Fang Guo - From the Departments of Psychological and Brain Sciences (B.X., R.L.T., F.G., T.G.B., A.K.J.), Pharmacology (A.K.J.), Internal Medicine (Y.Y., R.B.F.), and the François M. Abboud Cardiovascular Research Center (B.X., R.B.F., A.K.J.), University of Iowa, Iowa City
Terry G Beltz - From the Departments of Psychological and Brain Sciences (B.X., R.L.T., F.G., T.G.B., A.K.J.), Pharmacology (A.K.J.), Internal Medicine (Y.Y., R.B.F.), and the François M. Abboud Cardiovascular Research Center (B.X., R.B.F., A.K.J.), University of Iowa, Iowa City
Robert B Felder - From the Departments of Psychological and Brain Sciences (B.X., R.L.T., F.G., T.G.B., A.K.J.), Pharmacology (A.K.J.), Internal Medicine (Y.Y., R.B.F.), and the François M. Abboud Cardiovascular Research Center (B.X., R.B.F., A.K.J.), University of Iowa, Iowa City
Alan Kim Johnson - From the Departments of Psychological and Brain Sciences (B.X., R.L.T., F.G., T.G.B., A.K.J.), Pharmacology (A.K.J.), Internal Medicine (Y.Y., R.B.F.), and the François M. Abboud Cardiovascular Research Center (B.X., R.B.F., A.K.J.), University of Iowa, Iowa City
Resource Type: Journal article
Publication Details: Hypertension (Dallas, Tex. 1979), Vol.67(1), pp.163-170
DOI: 10.1161/HYPERTENSIONAHA.115.06263
PMID: 26573717
PMCID: PMC4834194
NLM abbreviation: Hypertension
ISSN: 0194-911X
eISSN: 1524-4563
Publisher: United States
Grant note: R01 HL096671 / NHLBI NIH HHS R01 MH080241 / NIMH NIH HHS MH-80241 / NIMH NIH HHS R01 HL098207 / NHLBI NIH HHS R01 HL073986 / NHLBI NIH HHS HL-073986 / NHLBI NIH HHS P01 HL014388 / NHLBI NIH HHS HL-096671 / NHLBI NIH HHS HL-14388 / NHLBI NIH HHS HL-98207 / NHLBI NIH HHS R01 AG025465 / NIA NIH HHS
Language: English
Date published: 01/2016
Academic Unit: Psychological and Brain Sciences; Iowa Neuroscience Institute; Cardiovascular Medicine; Neuroscience and Pharmacology; Neurology (Pediatrics); Health, Sport, and Human Physiology ; Internal Medicine
Record Identifier: 9984065479502771

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