Affiliation:
1. From the Department of Medicine and Therapeutics, Western Infirmary, Glasgow, UK.
Abstract
There is evidence in humans that hypertension and aging similarly impair endothelial function, although the mechanism remains unclear. Superoxide anion (O
2
−
) is a major determinant of nitric oxide (NO) bioavailability and thus endothelial function. We sought to determine the relationship between endothelial function, O
2
−
, 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). O
2
−
generation by aortic rings was measured before and after removal of the endothelium or incubation with
N
G
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). O
2
−
generation was significantly greater in old WKY compared with young WKY (
P
=0.0001). Removal of the endothelium and
N
G
nitro-
l
-arginine methyl ester treatment resulted in a significant reduction in O
2
−
generation in old SHRSP (
P
=0.009 and 0.001, respectively). Diphenyleneiodonium significantly reduced O
2
−
generation in 12-month WKY (
P
=0.008) and 12-month SHRSP (
P
=0.009). Apocynin attenuated O
2
−
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. O
2
−
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 O
2
−
.
Publisher
Ovid Technologies (Wolters Kluwer Health)
Cited by
399 articles.
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