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Perivascular inflammation drives sympathetic hyperinnervation and hypertension in obesity (682.1)
Author(s) -
Haddock Rebecca,
Matthaei Klaus,
Drummond Grant,
Hill Caryl
Publication year - 2014
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.28.1_supplement.682.1
Subject(s) - medicine , endocrinology , electrical impedance myography , inflammation , nerve plexus , nerve growth factor , sympathetic nervous system , mesenteric arteries , pathology , blood pressure , artery , receptor , vasodilation
Hypertension in obesity occurs as a result of abnormal increases in sympathetic nerve density over arteries controlling blood pressure; the causative factors underlying these changes are unknown. Here we examine the role of inflammatory cell infiltration to changes in perivascular nerve innervation over small mesenteric and renal arteries from C57BL/6 and Rag1‐/‐ mice fed a normal or high fat diet. Pressure myography, electrophysiology and videomicroscopy was used to measure intraluminal pressure, membrane potential, vessel diameter. Nerves were activated by electrical field stimulation. Immunohistochemistry was performed using antibodies against nerve growth factor (NGF), CD3+ (T cells) and F4/80 (macrophages). Sympathetic innervation was examined using anti‐synaptophysin (synaptic vesicles). Images were collected using confocal microscopy and analysed using Image J. Obese C57BL/6 mice were hypertensive. Nerve‐mediated contractions and excitatory junction potentials (EJP) were augmented (P<0.05) and the perivascular sympathetic nerve plexus was denser (P<0.05). Numbers of perivascular NGF‐producing immune cells (T cells and macrophages) were increased (P<0.05). Infiltration of these cells was shown to precede expansion of the nerve plexus (P<0.05). Rag1‐/‐ mice fed a HFD also became obese. However, numbers of perivascular NGF‐producing immune cells were not increased, arteries were not hyperinnervated and mice remained normotensive. Neurogenic hypertension in obesity occurs as a consequence of the infiltration of NGF positive immune cells to the vascular adventitia and expansion of the perivascular sympathetic nerve plexus. Grant Funding Source : Supported by the NHMRC to REH (466009)