Abstract 18791: Immune Cell Derived Nerve Growth Factor Initiates Neurogenic Hypertension in Obesity
Introduction: Hypertension in the obese is a rapidly increasing problem. It has both neurological and immunological antecedents, however the relationship between these is unclear.
Methods and Results: Here we used a mouse model of diet-induced obesity, pressure myography, immunohistochemistry, flow cytometry and radiotelemtry to demonstrate that immune cells, located within the vascular adventitia of arteries important for controlling blood pressure, produce nerve growth factor (NGF) and rapidly initiate growth of the perivascular sympathetic nerve plexus; which increases vascular tone and thereby elevates blood pressure. We also show that Rag1-/- mice lacking T and B cells do not develop hypertension when obesity is induced with a high fat diet (HFD) and show that their sympathetic innervation and vascular tone remains normal, suggesting that neurogenic hypertension in the obese likely occurs independently of weight gain. Furthermore, we show that the adoptive transfer of wildtype CD3+ T cells restores the sympathetic hyperinnervation and associated hypertension whereas the transfer of CD3+ T cells deficient in NGF had no effect on sympathetic innervation or blood pressure.
Conclusion: These results not only demonstrate the role of T cells in the genesis of obesity-related hypertension but also demonstrate the pivotal role of NGF in linking dysfunction of the immune and sympathetic nervous systems that characterize hypertension in the obese. a, Change in body weight b, nerve-mediated contraction amplitude recorded from pressurized small mesenteric arteries (1Hz, 30s) and c, systolic BP in mice in RAG-1-/- mice, which lack B and T cells, fed NCD or HFD. RAG-1-/-Tcell mice are recipients of CD3+ T cells via adoptive transfer. d, Perivascular nerve density (synaptophysin) over wholemount small mesenteric arteries from RAG-1-/- mice. Scale, 50μm.
Author Disclosures: G.R. Drummond: None. K.I. Matthai: None. S.K. Morton: None. A. Vinh: None. D.M. Ferens: None. J.I. Ellyard: None. C.G. Vinuesa: None. C.E. Hill: None. R.E. Haddock: None.
- © 2015 by American Heart Association, Inc.