Scavenging of NADPH oxidase‐derived superoxide anions improves depressed baroreflex sensitivity in spontaneously hypertensive rats

Abstract

In pathological conditions, such as hypertension, there is impairment in the autonomic control of blood pressure resulting in changes in baroreflex sensitivity. In the present study we tested the hypothesis that acute superoxide scavenging would restore the depressed baroreflex sensitivity (BRS) in spontaneously hypertensive rats (SHR). Male 10-week-old SHR (n=14) and their controls (Wistar-Kyoto (WKY) rats; n=14) underwent femoral artery and vein catheterization for conscious blood pressure recording and drug administration. The BRS was obtained by the drug-induced method using phenylephrine (8μg/kg, i.v.) and sodium nitroprusside (25μg/kg, i.v.) before and after the administration of tiron (30mg/kg, i.v.), a superoxide dismutase mimetic, or apocynin (30μg/kg), an NADPH oxidase inhibitor. Spontaneously hypertensive rats was significantly hypertensive compared with WKY rats (160±7 vs 105±2mmHg, respectively). However, there was no significant difference in heart rate between the two groups (388±10 vs 370±20b.p.m.). In addition, SHR exhibited a diminished BRS compared with WKY rats (-1.34±0.11 vs -2.91±0.20b.p.m./mmHg, respectively). Administration of tiron improved BRS in SHR (from -1.34±0.11 to 2.26±0.21b.p.m./mmHg), as did apocynin (to -2.14±0.23b.p.m./mmHg). Serum samples from SHR (n=20) and WKY rats (n=20) were collected for thiobarbituric acid-reactive substances assays before and after tiron or apocynin to confirm the reduction in oxidative stress. There was considerably greater oxidative stress in SHR compared with WKY rats (36.2±3.0 vs 13.3±2.6nmol/L, respectively). Both apocynin and tiron treatment reduced the oxidative stress in SHR (from 36.2±3.0 to 21.5±3.0nmol/L and from 37.2±3.9 to 21.9±1.6nmol/L, respectively). The data suggest that acute scavenging of NADPH oxidase-derived superoxide improves baroreflex sensitivity in SHR.