Aging, physical fitness and endothelial function: are all ultracentenarians marathon runners?

2004 ◽  
Vol 106 (3) ◽  
pp. 239-240 ◽  
Author(s):  
Guido GRASSI
Keyword(s):  
Nitric Oxide ◽  
Physical Fitness ◽  
Endothelial Function ◽  
Physical Training ◽  
Clinical Science ◽  
Marathon Runners ◽  
Elderly Individuals

This comment focuses on the background and implications of a study published in this issue of Clinical Science by Franzoni and colleagues showing that physical training improves nitric oxide availability and microvascular distensibility not only in young, but also in elderly, individuals. The main features of the study as well as its potential limitations will be also highlighted.

Age-Dependence in Alterations in Nitric Oxide Synthesis in Cardiovascular System during Adaptation to Physical Training

2010 ◽  
Vol 1 (4) ◽  
pp. 345-356 ◽  
Author(s):  
O. V. Bazilyuk ◽  
Anatolii V. Kotsuruba ◽  
Lyubov. G. Stepanenko ◽  
Sergey A. Talanov ◽  
Yu. P. Korchak ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Cardiovascular System ◽  
Physical Training ◽  
Nitric Oxide Synthesis ◽  
Age Dependence

Therapeutic Potential of Phosphodiesterase Inhibitors for Endothelial Dysfunction- Related Diseases

2020 ◽  
Vol 26 (30) ◽  
pp. 3633-3651 ◽  
Author(s):  
Javier Blanco-Rivero ◽  
Fabiano E. Xavier
Keyword(s):  
Nitric Oxide ◽  
Endothelial Dysfunction ◽  
Endothelial Function ◽  
Therapeutic Potential ◽  
Treatment Strategies ◽  
Phosphodiesterase Inhibitors ◽  
Developed Countries ◽  
Major Health Problem ◽  
Pde Inhibitors ◽  
Pharmaceutical Industries

Cardiovascular diseases (CVD) are considered a major health problem worldwide, being the main cause of mortality in developing and developed countries. Endothelial dysfunction, characterized by a decline in nitric oxide production and/or bioavailability, increased oxidative stress, decreased prostacyclin levels, and a reduction of endothelium-derived hyperpolarizing factor is considered an important prognostic indicator of various CVD. Changes in cyclic nucleotides production and/ or signalling, such as guanosine 3', 5'-monophosphate (cGMP) and adenosine 3', 5'-monophosphate (cAMP), also accompany many vascular disorders that course with altered endothelial function. Phosphodiesterases (PDE) are metallophosphohydrolases that catalyse cAMP and cGMP hydrolysis, thereby terminating the cyclic nucleotide-dependent signalling. The development of drugs that selectively block the activity of specific PDE families remains of great interest to the research, clinical and pharmaceutical industries. In the present review, we will discuss the effects of PDE inhibitors on CVD related to altered endothelial function, such as atherosclerosis, diabetes mellitus, arterial hypertension, stroke, aging and cirrhosis. Multiple evidences suggest that PDEs inhibition represents an attractive medical approach for the treatment of endothelial dysfunction-related diseases. Selective PDE inhibitors, especially PDE3 and PDE5 inhibitors are proposed to increase vascular NO levels by increasing antioxidant status or endothelial nitric oxide synthase expression and activation and to improve the morphological architecture of the endothelial surface. Thereby, selective PDE inhibitors can improve the endothelial function in various CVD, increasing the evidence that these drugs are potential treatment strategies for vascular dysfunction and reinforcing their potential role as an adjuvant in the pharmacotherapy of CVD.

Flow-mediated dilatation following wrist and upper arm occlusion in humans: the contribution of nitric oxide

2001 ◽  
Vol 101 (6) ◽  
pp. 629-635 ◽  
Author(s):  
Sagar N. DOSHI ◽  
Katerina K. NAKA ◽  
Nicola PAYNE ◽  
Christopher J.H. JONES ◽  
Moira ASHTON ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Endothelial Function ◽  
Brachial Artery ◽  
Peak Flow ◽  
Ultrasound Probe ◽  
Upper Arm ◽  
Flow Mediated Dilatation ◽  
Synthase Inhibitor ◽  
Increased Blood Flow ◽  
Similar Peak

Flow-mediated dilatation (FMD) of the brachial artery assessed by high-resolution ultrasound is widely used to measure endothelial function. However, the technique is not standardized, with different groups using occlusion of either the wrist or the upper arm to induce increased blood flow. The validity of the test as a marker of endothelial function rests on the assumption that the dilatation observed is endothelium-dependent and mediated by nitric oxide (NO). We sought to compare the NO component of brachial artery dilatation observed following wrist or upper arm occlusion. Dilatation was assessed before and during intra-arterial infusion of the NO synthase inhibitor NG-monomethyl-l-arginine (l-NMMA) following occlusion of (i) the wrist (distal to ultrasound probe) and (ii) the upper arm (proximal to ultrasound probe) for 5min in ten healthy males. Dilatation was significantly greater after upper arm occlusion (upper arm, 11.62±3.17%; wrist, 7.25±2.49%; P = 0.003). During l-NMMA infusion, dilatation after wrist occlusion was abolished (from 7.25±2.49% to 0.16±2.24%; P < 0.001), whereas dilatation after upper arm occlusion was only partially attenuated (from 11.62±3.17% to 7.51±2.34%; P = 0.006). The peak flow stimulus was similar after wrist and upper arm occlusion. We conclude that dilatation following upper arm occlusion is greater than that observed after wrist occlusion, despite a similar peak flow stimulus. l-NMMA infusion revealed that FMD following wrist occlusion is mediated exclusively by NO, while dilatation following upper arm occlusion comprises a substantial component not mediated by NO, most probably related to tissue ischaemia around the brachial artery. FMD following wrist occlusion may be a more valid marker of endothelial function than dilatation following upper arm occlusion.

scholarly journals Simultaneous Assessment of Endothelial Function, Nitric Oxide Synthase Activity, Nitric Oxide–Mediated Signaling, and Oxidative Stress in Individuals with and without Hypercholesterolemia

2008 ◽  
Vol 54 (2) ◽  
pp. 292-300 ◽  
Author(s):  
Renke Maas ◽  
Edzard Schwedhelm ◽  
Lydia Kahl ◽  
Huige Li ◽  
Ralf Benndorf ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Endothelial Function ◽  
Urinary Excretion ◽  
Indirect Evidence ◽  
No Oxidation ◽  
Whole Body ◽  
Gas Chromatography Mass Spectrometry ◽  
Synthesis Rate ◽  
No Production

Abstract Background: Endothelial function is impaired in hypercholesterolemia and atherosclerosis. Based on mostly indirect evidence, this impairment is attributed to reduced synthesis or impaired biological activity of endothelium-derived nitric oxide (NO). It was the aim of this study to directly estimate and compare whole-body NO production in normo- and hypercholesterolemia by applying a nonradioactive stable isotope dilution technique in vivo. Methods: We enrolled 12 normocholesterolemic and 24 hypercholesterolemic volunteers who were all clinically healthy. To assess whole-body NO synthesis, we intravenously administered l-[guanidino-(15N2)]-arginine and determined the urinary excretion of 15N-labeled nitrate, the specific end product of NO oxidation in humans, by use of gas chromatography-mass spectrometry. In addition, we measured flow-mediated vasodilation (FMD) of the brachial artery, expression of endothelial NOS (eNOS) in platelets, plasma concentration of the endogenous NOS inhibitor asymmetric dimethylarginine (ADMA), and urinary excretion of 8-isoprostaglandin F2α (8-iso-PGF2α). Results: After infusion of l-[guanidino-(15N2)]-arginine, cumulative excretion of 15N-labeled-nitrate during 48 h was 40% [95% CI 15%–66%] lower in hypercholesterolemic than normocholesterolemic volunteers [mean 9.2 (SE 0.8) μmol vs 15.4 (2.3) μmol/l, P = 0.003]. FMD was on average 36% [4%–67%] lower in hypercholesterolemic than normocholesterolemic volunteers [6.3 (4.0)% vs 9.4 (4.6)%, P = 0.027]. Normalized expression of NOS protein in platelets was also significantly lower in hypercholesterolemic volunteers, whereas there were no significant differences in plasma ADMA concentration or urinary excretion of 8-iso-PGF2α between the 2 groups. Conclusions: This study provides direct evidence for a decreased whole body NO synthesis rate in healthy people with hypercholesterolemia.

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