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Central inflammation induced by high fat diet sensitizes angiotensin II hypertension
Author(s) -
Xue Baojian,
Yu Yang,
Guo Fang,
Beltz Terry,
Felder Robert,
Johnson Alan
Publication year - 2015
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.29.1_supplement.986.3
Subject(s) - endocrinology , medicine , angiotensin ii , renin–angiotensin system , proinflammatory cytokine , sensitization , inflammation , tumor necrosis factor alpha , lamina terminalis , hypothalamus , blood pressure , downregulation and upregulation , chemistry , immunology , biochemistry , gene
Obesity is considered to be a chronic low‐grade inflammatory state. High fat diet (HFD) has been shown to promote the inflammation in the hypothalamus and to increase sympathetic activity. Our previous studies demonstrated that administration of either central tumor necrosis factor (TNF)‐α or a subpressor dose of angiotensin (ANG) II sensitizes subsequent ANG II‐elicited hypertension. The present study tested the hypothesis that feeding of HFD also induces the sensitization of the ANG II‐elicited hypertensive response. Male rats were prepared for telemetry recording of blood pressure (BP) and were given 1) normal fat diet (NFD, 10% fat) or 2) HFD (60% fat) or 3) HFD plus the TNF‐α synthesis inhibitorpentoxifylline (10 μg/h, ICV) for three weeks. The rats were then administrated ANG II (120 ng/kg/min, SC) for 2 weeks. HFD itself did not increase BP during the feeding period, but rats that received the HFD pretreatment responded with an enhanced hypertensive response to ANG II when compared to those that received the NFD (Δ39.4±3.7 mmHg vs. Δ25.4±2.8 mmHg). The TNF‐α synthesis inhibitor abolished sensitization produced by the HFD Δ24.9±4.8 mmHg). RT‐PCR analysis of tissue from the lamina terminalis and the paraventricular nucleus indicated that the HFD up‐regulated mRNA expression of several components of the renin‐angiotensin system and proinflammatory cytokines including renin, angiotensin type 1 receptor, angiotensin converting enzyme, TNF‐α and interleukin‐6. The results indicate that HFD‐induced sensitization of ANG II‐elicited hypertension is mediated by upregulation of central proinflammatory cytokines.