Exercise training reverses age-related decrements in endothelium-dependent dilation in skeletal muscle feed arteries

Trott, Daniel W.; Gündüz, Filiz; Laughlin, M. Harold; Woodman, Christopher R.

doi:10.1152/japplphysiol.91232.2008

Cited by 67 publications

(79 citation statements)

References 56 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…Apart from superoxide production, oxidative stress also can be regulated by antioxidant enzymes. SODs are enzymes that scavenge superoxide to form hydrogen peroxide and play a role in preserving NO bioavailability in the vasculature (32,47). In our study, db/db mice showed decreased endothelial function compared with Con, but TEMPOL incubation partially restored endothelial function in db/db, suggesting an increase of antioxidant enzymes may contribute to restoring endothelial function (Fig.…”

Section: Role Of Et In Endothelial Function Independent Of the Changementioning

confidence: 58%

“…Previous studies indicated that reactive oxygen species (ROS) such as superoxide (O 2 ·Ϫ ) readily react with NO to form peroxynitrate (ONOO Ϫ ), which results in decreased NO bioavailability (8,10,32,47). Oxidative stress is tightly regulated by a balance between production and removal facilitated by enzymatic activity in the healthy condition, whereas cell damage induced by excessive oxidative stress can contribute to diabetes-induced atherosclerosis and coronary artery disease (8, 9).…”

mentioning

confidence: 99%

See 1 more Smart Citation

Exercise training improves endothelial function via adiponectin-dependent and independent pathways in type 2 diabetic mice

Lee

Park

Dellsperger

et al. 2011

American Journal of Physiology-Heart and Circulatory Physiology

View full text Add to dashboard Cite

Lee S, Park Y, Dellsperger KC, Zhang C. Exercise training improves endothelial function via adiponectin-dependent and independent pathways in type 2 diabetic mice. Am J Physiol Heart Circ Physiol 301: H306 -H314, 2011. First published May 20, 2011 doi:10.1152/ajpheart.01306.2010.-Type 2 diabetes (T2D) is a leading risk factor for a variety of cardiovascular diseases including coronary heart disease and atherosclerosis. Exercise training (ET) has a beneficial effect on these disorders, but the basis for this effect is not fully understood. This study was designed to investigate whether the ET abates endothelial dysfunction in the aorta in T2D. Heterozygous controls (m Lepr db ) and type 2 diabetic mice (db/db; Lepr db ) were either exercise entrained by forced treadmill exercise or remained sedentary for 10 wk. Ex vivo functional assessment of aortic rings showed that ET restored acetylcholine-induced endothelial-dependent vasodilation of diabetic mice. Although the protein expression of endothelial nitric oxide synthase did not increase, ET reduced both IFN-␥ and superoxide production by inhibiting gp91 phox protein levels. In addition, ET increased the expression of adiponectin (APN) and the antioxidant enzyme, SOD-1. To investigate whether these beneficial effects of ET are APN dependent, we used adiponectin knockout (APNKO) mice. Indeed, impaired endothelial-dependent vasodilation occurred in APNKO mice, suggesting that APN plays a central role in prevention of endothelial dysfunction. APNKO mice also showed increased protein expression of IFN-␥, gp91 phox , and nitrotyrosine but protein expression of SOD-1 and -3 were comparable between wild-type and APNKO. These findings in the aorta imply that APN suppresses inflammation and oxidative stress in the aorta, but not SOD-1 and -3. Thus ET improves endothelial function in the aorta in T2D via both APN-dependent and independent pathways. This improvement is due to the effects of ET in inhibiting inflammation and oxidative stress (APN-dependent) as well as in improving antioxidant enzyme (APN-independent) performance in T2D. cardiovascular disease; inflammation; superoxide; vascular biology TYPE 2 DIABETES (T2D) is associated with impairment in endothelial function characterized by impaired endothelial-dependent vasodilation, increased inflammatory cell, and platelet adhesion in both rodents and humans (22,32,41,42,54). Accumulating evidence suggests that endothelial dysfunction is an early stage of atherosclerosis (11,41). Thus endothelial dysfunction with inflammatory cell and platelet adhesion may contribute to the development of atherosclerosis in T2D. Even though the mechanisms responsible for endothelial dysfunction are not fully elucidated, previous studies indicate that a decrease in nitric oxide (NO) bioavailability may play a central role in endothelial dysfunction in T2D (32,36,54).In addition, oxidative stress and chronic inflammation are important pathogenic factors in many diseases including T2D and cardiovascular diseases (CVD) such as stroke, cor...

show abstract

Section: Role Of Et In Endothelial Function Independent Of the Changementioning

confidence: 58%

mentioning

confidence: 99%

Exercise training improves endothelial function via adiponectin-dependent and independent pathways in type 2 diabetic mice

Lee

Park

Dellsperger

et al. 2011

American Journal of Physiology-Heart and Circulatory Physiology

View full text Add to dashboard Cite

show abstract

“…Differences in SOD-1, catalase, and glutathione peroxidase-1 (GPx-1) protein content in soleus muscle feed arteries were assessed by immunoblot analysis. Feed arteries were used in these analyses due to limitations of tissue volume in soleus muscle 1A arteriolar samples; however, aging-and training-induced adaptations of feed arteries generally parallel those of 1A arterioles (59,66). Vessels were isolated, snap frozen, and stored at Ϫ80°C.…”

Section: Evaluation Of Oonomentioning

confidence: 99%

Age and exercise training alter signaling through reactive oxygen species in the endothelium of skeletal muscle arterioles

Sindler

Reyes

Chen

et al. 2013

Journal of Applied Physiology

View full text Add to dashboard Cite

Sindler AL, Reyes R, Chen B, Ghosh P, Gurovich AN, Kang LS, Cardounel AJ, Delp MD, Muller-Delp JM. Age and exercise training alter signaling through reactive oxygen species in the endothelium of skeletal muscle arterioles. J Appl Physiol 114: [681][682][683][684][685][686][687][688][689][690][691][692][693] 2013. First published January 3, 2013; doi:10.1152/japplphysiol.00341.2012.-Exercise training ameliorates age-related impairments in endotheliumdependent vasodilation in skeletal muscle arterioles. Additionally, exercise training is associated with increased superoxide production. The purpose of this study was to determine the role of superoxide and superoxide-derived reactive oxygen species (ROS) signaling in mediating endothelium-dependent vasodilation of soleus muscle resistance arterioles from young and old, sedentary and exercise-trained rats. Young (3 mo) and old (22 mo) male rats were either exercise trained or remained sedentary for 10 wk. To determine the impact of ROS signaling on endothelium-dependent vasodilation, responses to acetylcholine were studied under control conditions and during the scavenging of superoxide and/or hydrogen peroxide. To determine the impact of NADPH oxidase-derived ROS, endothelium-dependent vasodilation was determined following NADPH oxidase inhibition. Reactivity to superoxide and hydrogen peroxide was also determined. Tempol, a scavenger of superoxide, and inhibitors of NADPH oxidase reduced endothelium-dependent vasodilation in all groups. Similarly, treatment with catalase and simultaneous treatment with tempol and catalase reduced endothelium-dependent vasodilation in all groups. Decomposition of peroxynitrite also reduced endothelium-dependent vasodilation. Aging had no effect on arteriolar protein content of SOD-1, catalase, or glutathione peroxidase-1; however, exercise training increased protein content of SOD-1 in young and old rats, catalase in young rats, and glutathione peroxidase-1 in old rats. These data indicate that ROS signaling is necessary for endothelium-dependent vasodilation in soleus muscle arterioles, and that exercise traininginduced enhancement of endothelial function occurs, in part, through an increase in ROS signaling. hydrogen peroxide; superoxide; peroxynitrite; nitric oxide; acetylcholine ENDOTHELIAL FUNCTION IN THE skeletal muscle resistance vasculature declines with age primarily due to decreased nitric oxide (NO) bioavailability (10,38,51,55). In feed arteries from soleus muscle, reductions in NO-dependent vasodilation are accompanied by reduced expression of endothelial NO synthase (eNOS) (65). In contrast, our laboratory has previously reported that NO-mediated vasodilation of soleus muscle arterioles declines with advancing age, despite an increase in eNOS protein levels (51). Thus the age-related decline in bioavailability of NO may be dependent on numerous other factors that regulate both NO production and degradation. eNOS activity, and subsequent NO production, is regulated by availability of substrate and cofactors, by protein-...

show abstract

“…Exercise or physical activity may contribute to improvement of insulin resistance via improved insulin action, improved vascular function via increase of nitric oxide (NO) bioavailability, and by increasing ROS-detoxification and decreasing ROS generation [48][49][50][51][52][53] . Since generation of ROS is a normal result of aerobic metabolism, it is efficiently removed by cellular anti-oxidant systems under physiological conditions.…”

Section: Role Of Exercise and Physical Activity In Antioxidant Processesmentioning

confidence: 99%

Effects of interventions on oxidative stress and inflammation of cardiovascular diseases

Lee¹,

Park²,

Zuidema³

et al. 2011

WJC

View full text Add to dashboard Cite

Excessive oxidative stress and low-grade chronic inflammation are major pathophysiological factors contributing to the development of cardiovascular diseases (CVD) such as hypertension, diabetes and atherosclerosis. Accumulating evidence suggests that a compromised antioxidant system can lead to excessive oxidative stress in cardiovascular related organs, resulting in cell damage and death. In addition, increased circulating levels of pro-inflammatory cytokines, such as tumor necrosis factor α, interleukin-6 and C-reactive protein, are closely related to morbidity and mortality of cardiovascular complications. Emerging evidence suggests that interventions including nutrition, pharmacology and exercise may activate expression of cellular anti-oxidant systems via the nuclear factor erythroid 2-related factor 2-Kelchlike ECH-associated protein 1 signaling pathway and play a role in preventing inflammatory processes in CVD. The focus of the present review is to summarize recent evidence showing the role of these anti-oxidant and anti-inflammatory interventions in cardiovascular disease. We believe that these findings may prompt new effective pathogenesis-oriented interventions, based on the exercise-induced protection from disease in the cardiovascular system, aimed at targeting oxidant stress and inflammation.

show abstract

Exercise training reverses age-related decrements in endothelium-dependent dilation in skeletal muscle feed arteries

Cited by 67 publications

References 56 publications

Exercise training improves endothelial function via adiponectin-dependent and independent pathways in type 2 diabetic mice

Exercise training improves endothelial function via adiponectin-dependent and independent pathways in type 2 diabetic mice

Age and exercise training alter signaling through reactive oxygen species in the endothelium of skeletal muscle arterioles

Effects of interventions on oxidative stress and inflammation of cardiovascular diseases

Contact Info

Product

Resources

About