244 Vascular BDNF expression and oxidative stress during aging and the development of chronic hypertension

Abstract

A Neurotrophin (NT): Brain-derived Neurotrophic Factor (BDNF) and the tropomyosin-related kinase (TrK) family of receptors play an important role in regulating vascular development and response to injury. But little is known about their role in vascular homeostasis in normal and pathological conditions. In the present study, we investigated the potential participation of the BDNF/TrK pathway and oxidative stress during the development of hypertension in an Spontaneously Hypertensive Rat (SHR) model. Systolic blood pressure (SBP) was measured (tail-cuff method) in male SHR and normotensive Wistar Kyoto rats (WKY) at 6 and 13 weeks of age. Plasma antioxidant capacity was measured by Electron Spin Resonance. Production of superoxide anion was assessed in aorta slices using a fluorescent oxidative probe: dihydroethidium.(DHE) Aorta NAD(P)H oxidase activity was determined by chemiluminescence. Plasma level of BDNF was assessed by an ELISA method and expression of BDNF, TrKB, p47phox, Angiotensin II AT1 receptor and MCP-1 was determined by immunochemistry. At 13 weeks, SHR became hypertensive (p<0.05). In 6-week-old SHR aorta, DHE staining was twice than in WKY aorta and the same pattern was observed at 13 weeks. At 13 weeks, NAD(P)H oxidase activity enhancement was associated with an increase in p47phox and AT1 expression and BDNF in aortic wall (p<0.05). Vascular MCP-1 expression increased with increasing blood pressure (p<0.05). In SHR rats, an increase in levels of oxidative stress occurs before elevation of blood pressure, but is not linked with an increase in NAD(P)H oxidase activity at 6 weeks. However, this oxidative stress seems to be associated with an increase in vascular BDNF during animals aging, and appears prematurely in SHR vessels. The relationship between BDNF/TrKB, oxidative stress and inflammation occurring in hypertension onset, remains to be elucidated.