165 - Effect of Nitrite and N-acetylcysteine Treatment on Blood Pressure, Arterial Stiffness and Vascular Function in Spontaneously Hypertensive Rats

Abstract

Introduction Reduced nitric oxide (NO) bioavailability and increased generation of reactive oxygen species and inflammation with advancing age play a major role in the development of cardiovascular disease (CVD) risk factors of hypertension, endothelial dysfunction and arterial stiffness. Therefore, increase in NO bioavailability by supplementing inorganic nitrite and improve in antioxidant defense system by supplementing N-acetylcysteine (NAC) could protect against the CVD. Hypertension is highly prevalent in a population and cause endothelial dysfunction and arterial stiffness. Hence spontaneously hypertensive rats (SHR) were used in this study as a model for hypertension-mediated endothelial dysfunction and arterial stiffness. Hypothesis Treatment of SHR with nitrite or NAC will reduce blood pressure, arterial stiffness, and endothelial dysfunction. Methods SHR (18 weeks) and normotensive Wistar Kyoto (WKY) rats were divided into 4 groups: 1) WKY, 2) SHR-cont, 3) SHR-nitrite and 4) SHR-NAC. Group 3 rats received nitrite (60 mg/L) in drinking water and group 4 rats received NAC pH 7.2 (1.2 g/L) for 3 months. Mean arterial pressure (MAP; tail-cuff method) and pulse wave velocity (PWV, a measure of arterial stiffness) were measured. Aortic endothelial function was determined with a wire myograph. Results MAP & PWV of SHR-cont were 1.8-fold and 1.6-fold higher compared with WKY respectively. MAP was modestly decreased in nitrite and NAC groups compared with that of SHR-cont. PWV did not decrease significantly with NAC or nitrite treatment. Endothelium dependent vasorelaxation was significantly decreased in SHR-cont compared with WKY. This decreased vasorelaxation was restored to WKY level in both nitrite and NAC groups. Conclusion Nitrite and NAC treatments completely protected against the hypertension induced endothelium dysfunction in SHR. Nitrite and NAC appears to be very promising dietary components to protect against age-associated endothelial dysfunction.