scholarly journals Sustained activation of AMPK ameliorates age-associated vascular endothelial dysfunction via a nitric oxide-independent mechanism

2012 ◽  
Vol 133 (5) ◽  
pp. 368-371 ◽  
Author(s):  
Lisa A. Lesniewski ◽  
Melanie C. Zigler ◽  
Jessica R. Durrant ◽  
Anthony J. Donato ◽  
Douglas R. Seals
Keyword(s):  
Nitric Oxide ◽  
Endothelial Dysfunction ◽  
Vascular Endothelial ◽  
Vascular Endothelial Dysfunction ◽  
Independent Mechanism ◽  
Sustained Activation

scholarly journals Nitrite supplementation reverses vascular endothelial dysfunction in old mice via improved nitric oxide bioavailability

2010 ◽  
Vol 24 (S1) ◽  
Author(s):  
Amy L Sindler ◽  
John W Calvert ◽  
Bradley S Fleenor ◽  
Melanie L Zigler ◽  
David J Lefer ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Endothelial Dysfunction ◽  
Vascular Endothelial ◽  
Vascular Endothelial Dysfunction ◽  
Old Mice ◽  
Nitric Oxide Bioavailability

scholarly journals Age-related comparative evaluation of laboratory-functional parameters of vascular endothelial dysfunction in patients with arterial hypertension

2012 ◽  
Vol 93 (1) ◽  
pp. 18-22
Author(s):  
A A Popova ◽  
S D Mayanskaya ◽  
I A Grebenkina ◽  
E B Luksha ◽  
L S Lebedeva
Keyword(s):  
Nitric Oxide ◽  
Antioxidant Activity ◽  
Endothelial Dysfunction ◽  
Arterial Hypertension ◽  
Blood Serum ◽  
Vascular Endothelium ◽  
Young Men ◽  
Vascular Endothelial ◽  
Vascular Endothelial Dysfunction ◽  
Brachial Artery Diameter

Aim. To conduct a comparative complex evaluation of the vasomotor and metabolic functions of the vascular endothelium in patients of different age groups with arterial hypertension. Methods. Examined were 98 young men and 60 elderly people with arterial hypertension of the I and II degree. The control group included 44 practically healthy young men and 45 elderly men. The endothelial function was assessed by Doppler measurements of brachial artery diameter at rest and during the test with reactive hyperemia and nitroglycerin, as well as by determining serum levels of the total amount of nitric oxide. Secondary stable products of lipid peroxidation were determined by the level of malondialdehyde. Antioxidant activity of blood was determined by evaluating the spontaneous chemiluminescence response. The diameter of the common carotid artery and the width of the intima/media complex was evaluated at rest using an ultrasound scanner. Results. Disturbance of the endothelium-dependent vasodilation in young and elderly patients with arterial hypertension of the I and II degree was accompanied by a significant decrease in production of endothelial nitric oxide. The expression of vascular endothelial dysfunction in patients of different ages with arterial hypertension of the I and II degree was in close correlation with the indicators of imbalance between the prooxidant activity and the antioxidant activity of blood, which manifested in an increase in the concentration of malondialdehyde in blood serum and in the decrease of the «antioxidant activity of blood/malondialdehyde content in blood serum» coefficient compared to groups of healthy individuals in response to pathological vasoconstriction. Conclusion. Arterial hypertension is accompanied by a progressive dysfunction of the vascular endothelium, which is more pronounced in the elderly due to reduced production of nitric oxide by the endothelium and due to the imbalance of the prooxidant-antioxidant system.

Vascular endothelial dysfunction: does tetrahydrobiopterin play a role?

2001 ◽  
Vol 281 (3) ◽  
pp. H981-H986 ◽  
Author(s):  
Zvonimir S. Katusic
Keyword(s):  
Nitric Oxide ◽  
Endothelial Dysfunction ◽  
Vascular Function ◽  
Ischemia Reperfusion ◽  
Vascular Endothelial ◽  
Vascular Endothelial Dysfunction ◽  
Vascular Effects ◽  
Beneficial Effects ◽  
Oxide Synthase

Tetrahydrobiopterin is one of the most potent naturally occurring reducing agents and an essential cofactor required for enzymatic activity of nitric oxide synthase (NOS). The exact role of tetrahydrobiopterin in the control of NOS catalytic activity is not completely understood. Existing evidence suggests that it can act as alosteric and redox cofactors. Suboptimal concentration of tetrahydrobiopterin reduces formation of nitric oxide and favors “uncoupling” of NOS leading to NOS-mediated reduction of oxygen and formation of superoxide anions and hydrogen peroxide. Recent findings suggest that accelerated catabolism of tetrahydrobiopterin in arteries exposed to oxidative stress may contribute to pathogenesis of endothelial dysfunction present in arteries exposed to hypertension, hypercholesterolemia, diabetes, smoking, and ischemia-reperfusion. Beneficial effects of acute and chronic tetrahydrobiopterin supplementation on endothelial function have been reported in experimental animals and humans. Furthermore, it appears that beneficial effects of some antioxidants (e.g., vitamin C) on vascular function could be mediated via increased intracellular concentration of tetrahydrobiopterin. In this review, the potential role of tetrahydrobiopterin in the pathogenesis of vascular endothelial dysfunction and mechanisms underlying beneficial vascular effects of tetrahydrobiopterin will be discussed.

scholarly journals Vascular endothelial dysfunction with aging: endothelin-1 and endothelial nitric oxide synthase

2009 ◽  
Vol 297 (1) ◽  
pp. H425-H432 ◽  
Author(s):  
Anthony J. Donato ◽  
Lindsey B. Gano ◽  
Iratxe Eskurza ◽  
Annemarie E. Silver ◽  
Phillip E. Gates ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Endothelial Dysfunction ◽  
Brachial Artery ◽  
Endothelial Nitric Oxide Synthase ◽  
Older Men ◽  
Vascular Endothelial ◽  
Vascular Endothelial Dysfunction ◽  
Healthy Men ◽  
Oxide Synthase ◽  
Endothelial Nitric Oxide

To determine whether impaired endothelium-dependent dilation (EDD) in older adults is associated with changes in the expression of major vasoconstrictor or vasodilator proteins in the vascular endothelium, endothelial cells (EC) were obtained from the brachial artery and peripheral veins of 56 healthy men, aged 18–78 yr. Brachial artery EC endothelin-1 (ET-1) [0.99 ± 0.10 vs. 0.57 ± 0.10 ET-1/human umbilical vein EC (HUVEC) intensity, P = 0.01] and serine 1177 phosphorylated endothelial nitric oxide synthase (PeNOS) (0.77 ± 0.09 vs. 0.44 ± 0.07 PeNOS/HUVEC intensity, P < 0.05) (quantitative immunofluorescence) were greater, and EDD (peak forearm blood flow to intrabrachial acetylcholine) was lower (10.2 ± 0.9 vs. 14.7 ± 1.7 ml·100 ml−1·min−1, P < 0.05) in older ( n = 18, 62 ± 1 yr) vs. young ( n = 15, 21 ± 1 yr) healthy men. EDD was inversely related to expression of ET-1 ( r = −0.39, P < 0.05). Brachial artery EC eNOS expression did not differ significantly with age, but tended to be greater in the older men (young: 0.23 ± 0.03 vs. older: 0.33 ± 0.07 eNOS/HUVEC intensity, P = 0.08). In the sample with venous EC collections, EDD (brachial artery flow-mediated dilation) was lower (3.50 ± 0.44 vs. 7.68 ± 0.43%, P < 0.001), EC ET-1 and PeNOS were greater ( P < 0.05), and EC eNOS was not different in older ( n = 23, 62 ± 1 yr) vs. young ( n = 27, 22 ± 1 yr) men. EDD was inversely related to venous EC ET-1 ( r = −0.37, P < 0.05). ET-1 receptor A inhibition with BQ-123 restored 60% of the age-related impairment in carotid artery dilation to acetylcholine in B6D2F1 mice (5–7 mo, n = 8; 30 mo, n = 11; P < 0.05). ET-1 expression is increased in vascular EC of healthy older men and is related to reduced EDD, whereas ET-1 receptor A signaling tonically suppresses EDD in old mice. Neither eNOS nor PeNOS is reduced with aging. Changes in ET-1 expression and bioactivity, but not eNOS, contribute to vascular endothelial dysfunction with aging.

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