Age-dependent endothelial dysfunction is associated with failure to increase plasma nitrite in response to exercise

Abstract

Age-dependent alterations of the vessel wall may predispose older individuals to increased cardiovascular pathology. Aging is associated with an impaired bioactivity of nitric oxide (NO). Plasma nitrite reflects NO-synthase activity under fasting conditions and is an important storage pool of NO. To test the hypothesis that aging is associated with an impaired capacity of the vasculature to increase plasma nitrite during exercise, 29 young and 28 old healthy individuals (25 +/- 1 years and 58 +/- 2 years; P < 0.001) without major cardiovascular risk factors were enrolled. Exercise stress was similar in both groups. Baseline nitrite did not differ (107 +/- 8 vs. 82 +/- 10 nmol/l, young vs. old; n.s.) although a trend toward higher nitrite levels in young individuals was seen. In young subjects, exercise increased plasma nitrite by 38 +/- 7% (P < 0.001) compared to only 13 +/- 8% (P = n.s.) in older subjects. L-NMMA blocked increases of nitrite. Endothelial function, as defined by flow-mediated-dilation (FMD) of the brachial artery via ultrasound, was impaired in older subjects (5.4 +/- 0.4% vs. 6.7 +/- 0.3%; P < 0.01). Multivariate analysis showed that age (P = 0.007), BMI (P = 0.010), and LDL (P = 0.021) were independent predictors of nitrite increase. The fact that aging is associated with an impaired capacity of the vasculature to adequately increase nitrite to physiological stimuli may contribute to attenuated maintenance and further deterioration of vascular homeostasis with aging.

Influence of Estimated Training Status on Anti and Pro-Oxidant Activity, Nitrite Concentration, and Blood Pressure in Middle-Aged and Older Women

“…The current study did not observe differences in this variable between middle-aged and older individuals, in accordance with the study of Lauer (Lauer et al, 2008), which showed no differences in plasma nitrite or nitrate, under baseline conditions, between middle-aged and older individuals. Nevertheless, Di Massimo et al (2006) found a high negative correlation between nitrite/nitrate and age.…”

Effects of aerobic exercise on the blood pressure, oxidative stress and eNOS gene polymorphism in pre-hypertensive older people

“…Not only a reduced eNOS activity but also NO-scavenging mechanisms and aging have been associated with an impaired capacity of the vasculature to adequately increase circulating nitrite in response to physiological stimulus (Doris 2002;Lauer et al 2002;Erbs et al 2003;Rutherford 2003;Touyz and Schiffrin 2004;Guzik et al 2005;Heltianu et al 2005;Fukai 2007;Lauer et al 2008). In the cardiovascular system, increased reactive oxygen species (ROS) production, such as O 2 -Á , can lead to endothelial dysfunction which contributes to vascular damage (Lounsbury et al 2000;Touyz and Schiffrin 2004;Rush et al 2005;Zalba et al 2005;Landmesser et al 2006).…”

“…In addition, elderly people have demonstrated lower NO metabolites (NOx) level than young people (Lauer et al 2008). However, there are few evidences about the relationship between aging and NOx levels and the effect of this relationship on blood pressure (BP).…”

Strategies to increase nitric oxide signalling in cardiovascular disease

“…It is noteworthy that both acute 237 and chronic exercise 238 lead to increased systemic levels of nitrite, similar to the levels achieved by dietary nitrate 33 . Thus, it is tempting to speculate that exerciseinduced effects on cardiovascular function could be at least partly mediated by the generation of nitrate and nitrite.…”