Superoxide excess in hypertension and aging - A common cause of endothelial dysfunction

Hamilton, C., Brosnan, M., McIntyre, M., Graham, D. and Dominiczak, A. (2001) Superoxide excess in hypertension and aging - A common cause of endothelial dysfunction. Hypertension, 37, pp. 529-534. (doi: 10.1161/01.HYP.37.2.529)

Abstract

here is evidence in humans that hypertension and aging similarly impair endothelial function, although the mechanism remains unclear. Superoxide anion (O2−) is a major determinant of nitric oxide (NO) bioavailability and thus endothelial function. We sought to determine the relationship between endothelial function, O2−, and age in normotensive Wistar-Kyoto (WKY) and stroke-prone spontaneously hypertensive rats (SHRSP). Aortic rings were removed from female WKY and SHRSP at 3 to 4 months (young) and 9 to 12 months (old). O2− generation by aortic rings was measured before and after removal of the endothelium or incubation with NG nitro-l-arginine methyl ester, diphenyleneiodonium, or apocynin. Levels of p22phox were studied with immunohistochemistry and used as a marker of NAD(P)H oxidase expression. NO bioavailability was significantly lower in old WKY compared with young WKY (P=0.0009) and in old SHRSP compared with young SHRSP (P=0.005). O2− generation was significantly greater in old WKY compared with young WKY (P=0.0001). Removal of the endothelium and NG nitro-l-arginine methyl ester treatment resulted in a significant reduction in O2− generation in old SHRSP (P=0.009 and 0.001, respectively). Diphenyleneiodonium significantly reduced O2− generation in 12-month WKY (P=0.008) and 12-month SHRSP (P=0.009). Apocynin attenuated O2− generation by older WKY (P=0.038) and SHRSP (P=0.028). p22phox was increased in older animals compared with young. We conclude that NO bioavailability decreases with age in female WKY and SHRSP. O2− generation increases with age in WKY and is higher in SHRSP and may contribute to the reduced NO by scavenging. NAD(P)H oxidase may contribute to the age-related increase in O2−

• Item Type: Articles
• Status: Published
• Refereed: Yes
• Glasgow Author(s) Enlighten ID: Hamilton, Dr Carlene and Dominiczak, Professor Anna and McIntyre, Dr Martin
• Authors: Hamilton, C., Brosnan, M., McIntyre, M., Graham, D., and Dominiczak, A.
• College/School: College of Medical Veterinary and Life Sciences; College of Medical Veterinary and Life Sciences > School of Cardiovascular & Metabolic Health
• Journal Name: Hypertension
• Publisher: American Heart Association
• ISSN: 0194-911X