Activation of central PPAR-γ attenuates angiotensin II-induced hypertension

Yang Yu; Bao-Jian Xue; Shun-Guang Wei; Zhi-Hua Zhang; Terry G Beltz; Fang Guo; Alan Kim Johnson; Robert B Felder

doi:10.1161/HYPERTENSIONAHA.115.05726

Back

Activation of central PPAR-γ attenuates angiotensin II-induced hypertension

Journal article

Open access

Peer reviewed

Activation of central PPAR-γ attenuates angiotensin II-induced hypertension

Yang Yu, Bao-Jian Xue, Shun-Guang Wei, Zhi-Hua Zhang, Terry G Beltz, Fang Guo, Alan Kim Johnson and Robert B Felder

Hypertension (Dallas, Tex. 1979), Vol.66(2), pp.403-411

08/2015

DOI: 10.1161/HYPERTENSIONAHA.115.05726

PMCID: PMC4498958

PMID: 26101342

Files and links (1)

url

http://doi.org/10.1161/HYPERTENSIONAHA.115.05726View

Open Access

Abstract

Inflammation and renin-angiotensin system activity in the brain contribute to hypertension through effects on fluid intake, vasopressin release, and sympathetic nerve activity. We recently reported that activation of brain peroxisome proliferator-activated receptor (PPAR)-γ in heart failure rats reduced inflammation and renin-angiotensin system activity in the hypothalamic paraventricular nucleus and ameliorated the peripheral manifestations of heart failure. We hypothesized that the activation of brain PPAR-γ might have beneficial effects in angiotensin II-induced hypertension. Sprague-Dawley rats received a 2-week subcutaneous infusion of angiotensin II (120 ng/kg per minute) combined with a continuous intracerebroventricular infusion of vehicle, the PPAR-γ agonist pioglitazone (3 nmol/h) or the PPAR-γ antagonist GW9662 (7 nmol/h). Angiotensin II+vehicle rats had increased mean blood pressure, increased sympathetic drive as indicated by the mean blood pressure response to ganglionic blockade, and increased water consumption. PPAR-γ mRNA in subfornical organ and hypothalamic paraventricular nucleus was unchanged, but PPAR-γ DNA-binding activity was reduced. mRNA for interleukin-1β, tumor necrosis factor-α, cyclooxygenase-2, and angiotensin II type 1 receptor was augmented in both nuclei, and hypothalamic paraventricular nucleus neuronal activity was increased. The plasma vasopressin response to a 6-hour water restriction also increased. These responses to angiotensin II were exacerbated by GW9662 and ameliorated by pioglitazone, which increased PPAR-γ mRNA and PPAR-γ DNA-binding activity in subfornical organ and hypothalamic paraventricular nucleus. Pioglitazone and GW9662 had no effects on control rats. The results suggest that activating brain PPAR-γ to reduce central inflammation and brain renin-angiotensin system activity may be a useful adjunct in the treatment of angiotensin II-dependent hypertension.

Angiotensin II - administration & dosage

Sympathetic Nervous System - drug effects

Male

PPAR gamma - metabolism

Thiazolidinediones - administration & dosage

Brain - metabolism

Sympathetic Nervous System - physiology

Hypertension - chemically induced

Hypertension - prevention & control

Blood Pressure - drug effects

Blood Pressure - physiology

Angiotensin II - adverse effects

Thiazolidinediones - pharmacology

Disease Models, Animal

Angiotensin II - pharmacology

Rats

Renin-Angiotensin System - physiology

Ventricular Remodeling - physiology

Rats, Sprague-Dawley

Hypertension - metabolism

Infusions, Subcutaneous

Animals

PPAR gamma - antagonists & inhibitors

Anilides - administration & dosage

Anilides - pharmacology

PPAR gamma - agonists

Renin-Angiotensin System - drug effects

Infusions, Intraventricular

Ventricular Remodeling - drug effects

Details

Title: Subtitle: Activation of central PPAR-γ attenuates angiotensin II-induced hypertension
Creators: Yang Yu - From the Department of Internal Medicine, Roy J and Lucille A Carver College of Medicine (Y.Y., S.-G.W., Z.-H.Z., R.B.F.) and Department of Psychological and Brain Sciences (B.-.J.X., T.G.B., F.G., A.K.J.), University of Iowa, Iowa City; and Research Service, Veterans Affairs Medical Center, Iowa City, IA (R.B.F.)
Bao-Jian Xue - From the Department of Internal Medicine, Roy J and Lucille A Carver College of Medicine (Y.Y., S.-G.W., Z.-H.Z., R.B.F.) and Department of Psychological and Brain Sciences (B.-.J.X., T.G.B., F.G., A.K.J.), University of Iowa, Iowa City; and Research Service, Veterans Affairs Medical Center, Iowa City, IA (R.B.F.)
Shun-Guang Wei - From the Department of Internal Medicine, Roy J and Lucille A Carver College of Medicine (Y.Y., S.-G.W., Z.-H.Z., R.B.F.) and Department of Psychological and Brain Sciences (B.-.J.X., T.G.B., F.G., A.K.J.), University of Iowa, Iowa City; and Research Service, Veterans Affairs Medical Center, Iowa City, IA (R.B.F.)
Zhi-Hua Zhang - From the Department of Internal Medicine, Roy J and Lucille A Carver College of Medicine (Y.Y., S.-G.W., Z.-H.Z., R.B.F.) and Department of Psychological and Brain Sciences (B.-.J.X., T.G.B., F.G., A.K.J.), University of Iowa, Iowa City; and Research Service, Veterans Affairs Medical Center, Iowa City, IA (R.B.F.)
Terry G Beltz - From the Department of Internal Medicine, Roy J and Lucille A Carver College of Medicine (Y.Y., S.-G.W., Z.-H.Z., R.B.F.) and Department of Psychological and Brain Sciences (B.-.J.X., T.G.B., F.G., A.K.J.), University of Iowa, Iowa City; and Research Service, Veterans Affairs Medical Center, Iowa City, IA (R.B.F.)
Fang Guo - From the Department of Internal Medicine, Roy J and Lucille A Carver College of Medicine (Y.Y., S.-G.W., Z.-H.Z., R.B.F.) and Department of Psychological and Brain Sciences (B.-.J.X., T.G.B., F.G., A.K.J.), University of Iowa, Iowa City; and Research Service, Veterans Affairs Medical Center, Iowa City, IA (R.B.F.)
Alan Kim Johnson - From the Department of Internal Medicine, Roy J and Lucille A Carver College of Medicine (Y.Y., S.-G.W., Z.-H.Z., R.B.F.) and Department of Psychological and Brain Sciences (B.-.J.X., T.G.B., F.G., A.K.J.), University of Iowa, Iowa City; and Research Service, Veterans Affairs Medical Center, Iowa City, IA (R.B.F.)
Robert B Felder - From the Department of Internal Medicine, Roy J and Lucille A Carver College of Medicine (Y.Y., S.-G.W., Z.-H.Z., R.B.F.) and Department of Psychological and Brain Sciences (B.-.J.X., T.G.B., F.G., A.K.J.), University of Iowa, Iowa City; and Research Service, Veterans Affairs Medical Center, Iowa City, IA (R.B.F.). robert-felder@uiowa.edu
Resource Type: Journal article
Publication Details: Hypertension (Dallas, Tex. 1979), Vol.66(2), pp.403-411
DOI: 10.1161/HYPERTENSIONAHA.115.05726
PMID: 26101342
PMCID: PMC4498958
NLM abbreviation: Hypertension
ISSN: 0194-911X
eISSN: 1524-4563
Publisher: United States
Grant note: R01 HL096671 / NHLBI NIH HHS R01 MH080241 / NIMH NIH HHS HL014388 / NHLBI NIH HHS HL073986 / NHLBI NIH HHS R01 HL098207 / NHLBI NIH HHS R01 HL073986 / NHLBI NIH HHS HL098207 / NHLBI NIH HHS P01 HL014388 / NHLBI NIH HHS MH080241 / NIMH NIH HHS HL096671 / NHLBI NIH HHS
Language: English
Date published: 08/2015
Academic Unit: Psychological and Brain Sciences; Iowa Neuroscience Institute; Neuroscience and Pharmacology; Neurology (Pediatrics); Health, Sport, and Human Physiology ; Internal Medicine
Record Identifier: 9984002355502771

Metrics

27 Record Views

37 Times Cited - Web of Science