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.

Determinants of short-term variation in arterial flow-mediated dilatation in healthy young men

2006 ◽  
Vol 110 (4) ◽  
pp. 475-482 ◽  
Author(s):  
Mikko J. Järvisalo ◽  
Laura Jartti ◽  
Jukka Marniemi ◽  
Tapani Rönnemaa ◽  
Jorma S. A. Viikari ◽  
...  
Keyword(s):  
Endothelial Function ◽  
Brachial Artery ◽  
Serum Insulin ◽  
Circadian Variation ◽  
Low Fat ◽  
Ultrasound Technique ◽  
Brachial Artery Diameter ◽  
Flow Mediated Dilatation ◽  
Hourly Variation ◽  
Fat Meal

Brachial artery FMD (flow-mediated dilatation) is widely used as a marker of systemic arterial endothelial function. FMD, however, shows considerable 25% day-to-day variation that hinders its clinical use. The reasons for this variability are poorly characterized. Therefore the present study was designed to clarify factors responsible for the hourly variation in endothelial function, including consuming a low-fat meal and circadian rhythms in endogenous hormonal levels. Brachial artery FMD, along with serum glucose, triacylglycerols (triglycerides) and levels of several hormones were measured six times per day on two separate days 1 week apart. On one day, the subjects (healthy males: n=12, mean age, 24 years) ate a light breakfast and a standardized lunch (23.5% fat, 48.7% carbohydrate and 27.8% protein). On the other day, they had a similar breakfast after which they fasted. Postprandial FMD values (both after breakfast and after lunch) were similar to baseline FMD. FMD showed a 28% hourly variation and 27% weekly variation. Variation in plasma levels of insulin (P=0.02) associated negatively and DHPG (3,4-dihydroxyphenylglycol) (P=0.001), a marker of sympathetic nervous activation, associated positively with variation in FMD. The effects of DHPG and insulin on FMD were independent of changes in baseline brachial artery diameter, although DHPG was also inversely associated with baseline diameter. Eating a regular low-fat meal does not have any measurable effects on brachial artery endothelial function. These data suggest that strict requirements for fasting conditions may be unnecessary when measuring peripheral endothelial function using the ultrasound technique. Circadian variation in serum insulin and sympathetic tone are physiological determinants of endothelial function.

Flow-mediated dilatation revisited

2005 ◽  
Vol 99 (4) ◽  
pp. 1623-1623 ◽  
Author(s):  
Robinson Joannides ◽  
Jeremy Bellien
Keyword(s):  
Nitric Oxide ◽  
Endothelial Function ◽  
Flow Mediated Dilation ◽  
Flow Mediated Dilatation ◽  
September Issue

This letter is in response to the Point:Counterpoint series “Flow-mediated dilation does/does not reflect nitric oxide-mediated endothelial function” that appeared in the September issue (vol. 99: 1233–1238, 2005; doi:10.1152/japplphysiol.00601.2005; http://jap.physiology.org/content/vol99/issue3/2005 ).

scholarly journals Cyclooxygenase and nitric oxide synthase dependence of cutaneous reactive hyperemia in humans

2007 ◽  
Vol 293 (1) ◽  
pp. H425-H432 ◽  
Author(s):  
Marvin S. Medow ◽  
Indu Taneja ◽  
Julian M. Stewart
Keyword(s):  
Nitric Oxide ◽  
Peak Flow ◽  
Reactive Hyperemia ◽  
Laser Doppler ◽  
Doppler Flowmetry ◽  
Time To Peak ◽  
Flow Parameters ◽  
Cox Inhibitor ◽  
Cutaneous Circulation ◽  
Synthase Inhibitor

We tested the hypothesis that cyclooxygenases (COXs) or COX products inhibit nitric oxide (NO) synthesis and thereby mask potential effects of NO on reactive hyperemia in the cutaneous circulation. We performed laser-Doppler flowmetry (LDF) with intradermal microdialysis in 12 healthy volunteers aged 19–25 yr. LDF was expressed as the percent cutaneous vascular conduction (%CVC) or as the maximum %CVC (%CVCmax) where CVC is LDF/mean arterial pressure. We tested the effects of the nonisoform-specific NO synthase inhibitor nitro-l-arginine (NLA, 10 mM), the nonspecific COX inhibitor ketorolac (Keto, 10 mM), combined NLA + Keto, and NLA + sodium nitroprusside (SNP, 28 mM) on baseline and reactive hyperemia flow parameters. We also examined the effects of isoproterenol, a β-adrenergic agonist that causes prostaglandin-independent vasodilation to correct for the increase in baseline flow caused by Keto. When delivered directly into the intradermal space, Keto greatly augments all aspects of the laser-Doppler flow response to reactive hyperemia: peak reactive hyperemic flow increased from 41 ± 5 to 77 ± 7%CVCmax, time to peak flow increased from 17 ± 3 to 56 ± 24 s, the area under the reactive hyperemic curve increased from 1,417 ± 326 to 3,376 ± 876%CVCmax·s, and the time constant for the decay of peak flow increased from 100 ± 23 to 821 ± 311 s. NLA greatly attenuates the Keto response despite exerting no effects on baseline LDF or on reactive hyperemia when given alone. Low-dose NLA + SNP duplicates the Keto response. Isoproterenol increased baseline and peak reactive flow. These results suggest that COX inhibition unmasks NO dependence of reactive hyperemia in human cutaneous circulation.

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

2001 ◽  
Vol 101 (6) ◽  
pp. 629 ◽  
Author(s):  
Sagar N. DOSHI ◽  
Katerina K. NAKA ◽  
Nicola PAYNE ◽  
Christopher J. H. JONES ◽  
Moira ASHTON ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Upper Arm ◽  
Flow Mediated Dilatation

scholarly journals Coronary vasomotor responses to isometric handgrip exercise are primarily mediated by nitric oxide: a noninvasive MRI test of coronary endothelial function

2015 ◽  
Vol 308 (11) ◽  
pp. H1343-H1350 ◽  
Author(s):  
Allison G. Hays ◽  
Micaela Iantorno ◽  
Sahar Soleimanifard ◽  
Angela Steinberg ◽  
Michael Schär ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Endothelial Function ◽  
Handgrip Exercise ◽  
Isometric Handgrip ◽  
Cross Sectional ◽  
Coronary Endothelial Function ◽  
Cell Release ◽  
Isometric Handgrip Exercise ◽  
Translational Strategies ◽  
Synthase Inhibitor

Endothelial cell release of nitric oxide (NO) is a defining characteristic of nondiseased arteries, and abnormal endothelial NO release is both a marker of early atherosclerosis and a predictor of its progression and future events. Healthy coronaries respond to endothelial-dependent stressors with vasodilatation and increased coronary blood flow (CBF), but those with endothelial dysfunction respond with paradoxical vasoconstriction and reduced CBF. Recently, coronary MRI and isometric handgrip exercise (IHE) were reported to noninvasively quantify coronary endothelial function (CEF). However, it is not known whether the coronary response to IHE is actually mediated by NO and/or whether it is reproducible over weeks. To determine the contribution of NO, we studied the coronary response to IHE before and during infusion of NG-monomethyl-l-arginine (l-NMMA, 0.3 mg·kg−1·min−1), a NO-synthase inhibitor, in healthy volunteers. For reproducibility, we performed two MRI-IHE studies ∼8 wk apart in healthy subjects and patients with coronary artery disease (CAD). Changes from rest to IHE in coronary cross-sectional area (%CSA) and diastolic CBF (%CBF) were quantified. l-NMMA completely blocked normal coronary vasodilation during IHE [%CSA, 12.9 ± 2.5 (mean ± SE, placebo) vs. −0.3 ± 1.6% (l-NMMA); P < 0.001] and significantly blunted the increase in flow [%CBF, 47.7 ± 6.4 (placebo) vs. 10.6 ± 4.6% (l-NMMA); P < 0.001]. MRI-IHE measures obtained weeks apart strongly correlated for CSA ( P < 0.0001) and CBF ( P < 0.01). In conclusion, the normal human coronary vasoactive response to IHE is primarily mediated by NO. This noninvasive, reproducible MRI-IHE exam of NO-mediated CEF promises to be useful for studying CAD pathogenesis in low-risk populations and for evaluating translational strategies designed to alter CAD in patients.

Deletion polymorphism in the α2B-adrenergic receptor gene is associated with flow-mediated dilatation of the brachial artery

2002 ◽  
Vol 103 (5) ◽  
pp. 517-524 ◽  
Author(s):  
Paula HEINONEN ◽  
Laura JARTTI ◽  
Mikko J. JÄRVISALO ◽  
Ullamari PESONEN ◽  
Jaakko A. KAPRIO ◽  
...  
Keyword(s):  
Carotid Artery ◽  
Endothelial Function ◽  
Brachial Artery ◽  
Adrenergic Receptor ◽  
Intima Media Thickness ◽  
Deletion Variant ◽  
Media Thickness ◽  
Increased Risk ◽  
Flow Mediated Dilatation ◽  
Carotid Artery Compliance

A deletion variant of the α2B-adrenergic receptor (α2B-AR) has been associated with an increased risk of acute cardiac events in middle-aged men. Our aim was to determine the possible associations between the α2B-AR gene deletion variant and indicators of subclinical atherosclerosis in the brachial and carotid arteries. A total of 148 middle-aged men participating in an epidemiological twin study on risk factors for subclinical coronary heart disease were genotyped using PCR. Flow-mediated dilatation (FMD) of the brachial artery, carotid artery compliance and carotid intima-media thickness were measured using high-resolution ultrasound. FMD was 6.2±5.0% in subjects with the I/I (insertion/insertion) genotype, 5.5±4.1% in the I/D (insertion/deletion) group and 4.1±3.8% in the D/D (deletion/deletion) group (P = 0.03 for trend). In multivariate regression analysis controlling for age, presence of hypertension, smoking, use of angiotensin-converting enzyme inhibitors and plasma levels of low-density lipoprotein cholesterol and lipoprotein (a), the association between the α2B-AR genotype and FMD remained significant (P = 0.04 for trend). The α2B-AR genotype was not associated with intima-media thickness or carotid artery compliance. These findings indicate that subjects homozygous for the deletion allele of α2B-AR appear to have an increased risk of impaired endothelial function, which may provide an explanation for the previously observed increased risk of myocardial infarction in male subjects with this genotype. It is not known whether the association of the α2B-AR polymorphism with endothelial function is direct, or is mediated via altered sympathetic activation.

The impact of different supervised exercise regimens on endothelial function in patients with intermittent claudication

Vascular ◽  
2014 ◽  
Vol 23 (6) ◽  
pp. 561-569 ◽  
Author(s):  
Christopher L Delaney ◽  
Michelle D Miller ◽  
Richard B Allan ◽  
J Ian Spark
Keyword(s):  
Nitric Oxide ◽  
Exercise Training ◽  
Endothelial Function ◽  
Walking Distance ◽  
Reactive Hyperaemia ◽  
Supervised Exercise ◽  
Flow Mediated Dilatation ◽  
Group 2 ◽  
The Impact ◽  
Group 1

Background and objectives The impact of supervised exercise training on endothelial function in patients with intermittent claudication is unclear. This study assesses the impact of treadmill-based supervised exercise training alone or in combination with resistance training on pain free walking distance, flow-mediated dilatation, reactive hyperaemia index, nitric oxide and asymmetric dimethylarginine. Methods Thirty-five patients with intermittent claudication were randomised to 12 weeks of treadmill-only supervised exercise training (Group 1) or a combination of treadmill and lower-limb resistance supervised exercise training (Group 2). Pain free walking distance was assessed by six-minute walk test. Endothelial function was assessed by brachial artery flow-mediated dilatation, reactive hyperaemia index and serum analysis of asymmetric dimethylarginine and nitric oxide. Results Pain free walking distance improved within Group 1 (160 m to 204 m, p = 0.03) but not Group 2 (181 m to 188 m, p = 0.82), no between group difference. No significant change in flow-mediated dilatation or reactive hyperaemia index in either group. Nitric oxide decreased in Group 1 (15.0 µmol/L to 8.3 µmol/L, p = 0.003) but not Group 2 (11.2 µmol/L to 9.1 µmol/L, p = 0.14), p = 0.07 between groups. Asymmetric dimethylarginine decreased in Group 2 (0.61 µmol/L to 0.56 µmol/L, p = 0.03) but not Group 1 (0.58 µmol/l to 0.58 µmol/L, p = 0.776), no between group difference. Conclusion Supervised exercise training does not improve endothelial function as measured by flow-mediated dilatation, reactive hyperaemia index and nitric oxide bioavailability.

Inhibition of Acetylcholinesterase Selectively Potentiates NG-Monomethyl-l-Arginine-Resistant Actions of Acetylcholine in Human Forearm Vasculature

1995 ◽  
Vol 88 (1) ◽  
pp. 111-117 ◽  
Author(s):  
P. J. Chowienczyk ◽  
J. R. Cockcroft ◽  
J. M. Ritter
Keyword(s):  
Nitric Oxide ◽  
Blood Flow ◽  
Brachial Artery ◽  
Acetylcholinesterase Inhibitor ◽  
Sensory Nerve ◽  
High Dose ◽  
Nitric Oxide Synthase Inhibitor ◽  
Blood Flows ◽  
Human Forearm ◽  
Synthase Inhibitor

1. NG-monomethyl-l-arginine (l-NMMA, a nitric oxide synthase inhibitor) inhibits vasodilator responses to acetylcholine but not methacholine in human forearm vasculature. To investigate whether this difference results from the relative susceptibility of these agonists to hydrolysis by acetylcholinesterase, we studied vasodilator responses to brachial artery administration of acetylcholine alone and in the presence of the acetylcholinesterase inhibitor edrophonium. 2. Vasodilator responses to constant-rate brachial artery infusions of acetylcholine were biphasic, with an initial peak response fading over 2 min to a plateau. Fade [(peak—plateau)/peak × 100%] was dose dependent (P < 0.02), ranging from 43 ± 7% (mean ± SEM) at low dose (16 nmol/min) to 9 ± 8% at high dose (83 nmol/min). 3. Edrophonium (0.5 μmol/min intra-arterially) alone produced no change in forearm blood flow but increased blood flow responses to acetylcholine (P < 0.01), causing an approximately 10-fold reduction in the dose required to increase plateau blood flow by 10 ml min−1 100 ml−1. 4. Responses to low doses of acetylcholine alone (16 and 41 nmol/min) faded more (P < 0.01) than those to doses of acetylcholine with edrophonium chosen to produce similar plateau blood flows. Responses to acetylcholine (41 nmol/min) also faded more (P < 0.01) than those to methacholine (5 nmol/min), producing matched plateau flows. 5. Peak and plateau responses to acetylcholine (41 nmol/min) were reduced (P < 0.01) by similar amounts (47 ± 15% and 37 ± 13% respectively, P = 0.39) by coinfusion of l-NMMA (4 μmol/min). l-NMMA inhibited responses to acetylcholine more than matched responses to acetylcholine with edrophonium (P < 0.01). 6. These results suggest that the actions of acetylcholine in human forearm resistance vessels are mediated both through an l-NMMA-sensitive pathway (l-arginine/nitric oxide pathway) that exhibits biphasic characteristics and through an l-NMMA-resistant pathway. The l-NMMA-resistant pathway is selectively potentiated by edrophonium. Inhibition of acetylcholinesterase by edrophonium may increase concentrations of acetylcholine deep to the endothelium and favour NO-independent actions on smooth muscle or sensory nerve endings mediating vasodilatation.

scholarly journals Endothelial dysfunction and hypertension

2008 ◽  
Vol 14 (4) ◽  
pp. 315-319 ◽  
Author(s):  
A. N. Shishkin ◽  
M. L. Lyndina
Keyword(s):  
High Resolution ◽  
Endothelial Dysfunction ◽  
Endothelial Function ◽  
Arterial Hypertension ◽  
Brachial Artery ◽  
Flow Mediated Dilatation

The aim of our study was to evaluate whether abnormal endothelial function is present in patients with arterial hypertension. Endothelial function was assessed by measuring flow-mediated dilatation (FMD) and nitroglycerin-mediated dilatation of the brachial artery using high-resolution ultrasound. In the group of subjects with arterial hypertension endothelial function was significantly impaired (FMD 9,26%), whereas nitroglycerin-mediated dilatation was normal.

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