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In Renovascular Hypertension, TNF‐α Type‐1 Receptors in the Area Postrema Mediate Increases in Cardiac and Renal Sympathetic Nerve Activity and Blood Pressure
Author(s) -
Korim Willian S,
Elsaafien Khalid,
Basser Jeremy,
Setiadi Anthony,
May Clive N,
Yao Song T
Publication year - 2019
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.2019.33.1_supplement.565.1
Subject(s) - area postrema , medicine , rostral ventrolateral medulla , renovascular hypertension , blood pressure , endocrinology , receptor , heart rate
Neuroinflammation is a common feature in renovascular, obesity‐related, and angiotensin II mediated hypertension. There is evidence that increased release of the pro‐inflammatory cytokine tumour necrosis factor‐α (TNF‐α) contributes to the development of the hypertension, but the underlying neural mechanisms are unclear. In rats with renovascular hypertension, area postrema neurons that expressed TNF‐α type‐1 receptor (TNFR1) remained constantly activated (expressed c‐Fos) and injection of TNFR1 neutralizing antibody into the area postrema returned blood pressure (systolic: ~151 mmHg) to normotensive levels (systolic: ~108 mmHg). Nanoinjection of TNF‐α (100 pg/50 nl) into the area postrema of anaesthetized normotensive rats increased blood pressure (~16 mmHg) and sympathetic nerve activity, predominantly to the heart (~53%), but also to the kidneys (~35%). These responses were abolished by prior injection of a TNFR1 neutralizing antibody (1 ng/50 nl) within the same site. TNFR1 were expressed in the somata of neurons activated by TNF‐α that were retrogradely labelled from the rostral ventrolateral medulla. These findings indicate that in renovascular hypertension, activation of TNFR1 expressing neurons in the area postrema by TNF‐α contributes to the sustained blood pressure in rats. This is mediated, in part, by projections to the rostral ventrolateral medulla and an increase in both cardiac and renal sympathetic nerve activity. Support or Funding Information This work was supported by the National Health and Medical Research Council of Australia (GNT 1079680 to STY), the High Blood Pressure Research Council of Australia, the Rebecca L Cooper Medical Foundation, the Wade Institute and Ormond College ‐ University of Melbourne (to WSK) and the Victorian Government through the Operational Infrastructure Scheme. KE and AS are supported by the Australian Government Research Training Program Scholarships. STY is supported by an Australian Research Council Future Fellowship (FT170100363).Effects of injection of TNF‐α into the AP on cardiac and renal sympathetic nerve activity.This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal .