Renin‐Angiotensin System and NAD(P)H Oxidase Activation in the Rostral Ventrolateral Medulla are involved in the Further Blood Pressure Elevation on High Sodium Diet in Spontaneously Hypertensive rats

Abstract

Background: High salt diet (HS) causes sympathetic hyperactivity and increases blood pressure (BP) in spontaneously hypertensive rats (SHR). We previously demonstrated the reactive oxygen species (ROS) in the rostral ventrolateral medulla (RVLM) was increased more in SHR on a HS (8%) than a regular salt diet (0.5%: RS). This study aimed to elucidate whether the increased ROS in the RVLM of HS‐SHR is associated with central NAD(P)H oxidase activation and the pressor response on an HS diet is involved in renin‐angiotensin system (RAS) activation.Methods and Results: Male SHR were fed an HS or RS diet for 6 weeks. Systolic BP was significantly higher in HS‐SHR than in RS‐SHR (244±15 mmHg vs 188±20 mmHg at 12 weeks old, n=8, P<0.05). The angiotensin II type1 receptor (AT1R) protein expression in the RVLM was significantly increased more in HS‐SHR than in RS‐SHR (5.1±0.5 vs 3.4±0.3, n=6, P<0.05). The AT1R antagonist (valsartan) microinjected bilaterally into the RVLM induced a significantly greater BP depression in HS‐SHR than in RS‐SHR (Δ MAP/basal MAP: −13.2±2.1 % vs −20.9±2.2% n=5, P<0.05). NAD(P)H oxidase activity was significantly higher in HS‐SHR than in RS‐SHR (1.53±0.10 vs 1.25±0.10, n=9, P<0.05).Conclusions: These results suggest that the pressor response of SHR on an HS diet is mediated by RAS activation and the ROS increase is involved in the enhanced NAD(P)H oxidase activation in the RVLM.