(Hypertension. 2001;37:529.)
© 2001 American Heart Association, Inc.
Scientific Contributions |
Superoxide Excess in Hypertension and Aging
A Common Cause of Endothelial Dysfunction
From the Department of Medicine and Therapeutics, Western Infirmary, Glasgow, UK.
Correspondence to Dr Carlene A. Hamilton, Department of Medicine and Therapeutics, Gardiner Institute, Western Infirmary, Glasgow G11 6NT, UK. E-mail cah1p{at}clinmed.gla.ac.uk
There 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-.
Key Words: endothelium • nitric oxide • hypertension, experimental • aging
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D. M. Attia, A. M. G. Verhagen, E. S. G. Stroes, E. E. van Faassen, H.-J. Grone, S. J. De Kimpe, H. A. Koomans, B. Braam, and J. A. Joles Vitamin E Alleviates Renal Injury, but Not Hypertension, during Chronic Nitric Oxide Synthase Inhibition in Rats J. Am. Soc. Nephrol., December 1, 2001; 12(12): 2585 - 2593. [Abstract] [Full Text] [PDF]
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G. Zalba, G. S. Jose, M. U. Moreno, M. A. Fortuno, A. Fortuno, F. J. Beaumont, and J. Diez Oxidative Stress in Arterial Hypertension: Role of NAD(P)H Oxidase Hypertension, December 1, 2001; 38(6): 1395 - 1399. [Abstract] [Full Text] [PDF]
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S. Wassmann, U. Laufs, D. Stamenkovic, W. Linz, J.-P. Stasch, K. Ahlbory, R. Rosen, M. Bohm, and G. Nickenig Raloxifene Improves Endothelial Dysfunction in Hypertension by Reduced Oxidative Stress and Enhanced Nitric Oxide Production Circulation, April 30, 2002; 105(17): 2083 - 2091. [Abstract] [Full Text] [PDF]
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