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

Abstract

Brain-derived neurotrophic factor (BDNF) and TrK receptors play an important role in vascular development and response to injury. In this study, we investigated the participation of the BDNF/TrK pathway and oxidative stress during the development of hypertension in spontaneously hypertensive rats (SHR). In SHR and normotensive rats (WKY) at 6 and 13 weeks of age, we studied (i) plasma antioxidant capacity, (ii) production of superoxide and NAD(P)H oxidase activity in aorta (iii) plasma BDNF and vascular expression of BDNF, TrKB, NAD(P)H oxidase subunits, AT1 receptor, and MCP-1. In 6- and 13-week-old SHR aorta, superoxide level was twice than in WKY aorta. At 13 weeks, when blood pressure in SHR was 60 mmHg higher in SHR than in WKY, an enhancement of NAD(P)H oxidase activity in SHR was associated with an increase in p47phox, AT1, and BDNF expression in vessels. MCP-1 expression increased with blood pressure. Our study demonstrated that in SHR rats, an increase in levels of vascular oxidative stress and in aortic BDNF and TrKB expression occurs prior to the rise in blood pressure, while a reinforcement of vascular and circulating oxidative stress markers is brought about later by hypertension.