Endothelial dysfunction and hypertension

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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Ascorbic Acid does not Improve Endothelium-Dependent Flow-mediated Dilatation of the Brachial Artery in Patients with Raynaud’s Phenomenon Secondary to Systemic Sclerosis

International Journal for Vitamin and Nutrition Research ◽

10.1024/0300-9831.73.1.3 ◽

2003 ◽

Vol 73 (1) ◽

pp. 3-7 ◽

Cited By ~ 22

Author(s):

M. E. Mavrikakis ◽

J. P. Lekakis ◽

M. Papamichael ◽

K. S. Stamatelopoulos ◽

Ch. C. Kostopoulos ◽

...

Keyword(s):

Ascorbic Acid ◽

Smooth Muscle ◽

Systemic Sclerosis ◽

Endothelial Dysfunction ◽

Brachial Artery ◽

Raynaud’S Phenomenon ◽

Raynaud's Phenomenon ◽

Water Soluble ◽

Placebo Administration ◽

Flow Mediated Dilatation

Previous studies have shown that patients with Raynaud’s phenomenon secondary to systemic sclerosis present abnormal endothelial function; the mechanisms responsible for the endothelial dysfunction are unknown but increased vascular oxidative stress could be a possible cause. The hypothesis that a potent water-soluble antioxidant can reverse endothelial dysfunction in these patients was tested in the present study. We examined 11 female patients with Raynaud’s phenomenon secondary to systemic sclerosis and ten healthy control women by ultrasound imaging of the brachial artery to assess flow-mediated (endothelium-dependent) and nitrate-induced (endothelium-independent) vasodilatation. Flow-mediated dilatation and nitrate-induced dilatation were significantly reduced in patients with Raynaud’s phenomenon, indicating abnormal endothelial and smooth muscle cell function. Patients with Raynaud’s phenomenon entered a double-blind, randomized, crossover placebo-controlled trial and received orally 2 g of ascorbic acid or placebo; vascular studies were repeated two hours after ascorbic acid or placebo administration. Flow-mediated dilatation did not improve after ascorbic acid (1.6 ± 2.2% to 2.2 ± 2.5%, ns) or placebo administration (1.2 ± 1,9% to 1.7 ± 1.4%, ns); also nitrate-induced dilatation was similar after ascorbic acid or placebo (16 ± 7.4% vs 17 ± 8%, ns), suggesting no effect of ascorbic acid on endothelial and vascular smooth muscle function. In conclusion, ascorbic acid does not reverse endothelial vasomotor dysfunction in the brachial circulation of patients with Raynaud’s phenomenon secondary to systemic sclerosis. The use of different antioxidants or different dosing of ascorbic acid may be required to show a beneficial effect on endothelial vasodilator function.

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

Clinical Science ◽

10.1042/cs1010629 ◽

2001 ◽

Vol 101 (6) ◽

pp. 629-635 ◽

Cited By ~ 180

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.

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

Clinical Science ◽

10.1042/cs20050333 ◽

2006 ◽

Vol 110 (4) ◽

pp. 475-482 ◽

Cited By ~ 28

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.

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Fenofibrate improves endothelial function in the brachial artery and forearm resistance arterioles of statin-treated Type 2 diabetic patients

Clinical Science ◽

10.1042/cs20090568 ◽

2010 ◽

Vol 118 (10) ◽

pp. 607-615 ◽

Cited By ~ 29

Author(s):

Sandra J. Hamilton ◽

Gerard T. Chew ◽

Timothy M.E. Davis ◽

Gerald F. Watts

Keyword(s):

Endothelial Dysfunction ◽

Endothelial Function ◽

Statin Therapy ◽

Brachial Artery ◽

Ldl Cholesterol ◽

Density Lipoprotein ◽

Diabetic Patients ◽

Type 2 Diabetic Patients ◽

Type 2 Diabetic

Dyslipidaemia contributes to endothelial dysfunction and CVD (cardiovascular disease) in Type 2 diabetes mellitus. While statin therapy reduces CVD in these patients, residual risk remains high. Fenofibrate corrects atherogenic dyslipidaemia, but it is unclear whether adding fenofibrate to statin therapy lowers CVD risk. We investigated whether fenofibrate improves endothelial dysfunction in statin-treated Type 2 diabetic patients. In a cross-over study, 15 statin-treated Type 2 diabetic patients, with LDL (low-density lipoprotein)-cholesterol <2.6 mmol/l and endothelial dysfunction [brachial artery FMD (flow-mediated dilatation) <6.0%] were randomized, double-blind, to fenofibrate 145 mg/day or matching placebo for 12 weeks, with 4 weeks washout between treatment periods. Brachial artery FMD and endothelium-independent NMD (nitrate-mediated dilatation) were measured by ultrasonography at the start and end of each treatment period. PIFBF (post-ischaemic forearm blood flow), a measure of microcirculatory endothelial function, and serum lipids, lipoproteins and apo (apolipoprotein) concentrations were also measured. Compared with placebo, fenofibrate increased FMD (mean absolute 2.1±0.6 compared with −0.3±0.6%, P=0.04), but did not alter NMD (P=0.75). Fenofibrate also increased maximal PIFBF {median 3.5 [IQR (interquartile range) 5.8] compared with 0.3 (2.1) ml/100 ml/min, P=0.001} and flow debt repayment [median 1.0 (IQR 3.5) compared with −1.5 (3.0) ml/100 ml, P=0.01]. Fenofibrate lowered serum cholesterol, triacylgycerols (triglycerides), LDL-cholesterol, apoB-100 and apoC-III (P≤0.03), but did not alter HDL (high-density lipoprotein)-cholesterol or apoA-I. Improvement in FMD was inversely associated with on-treatment LDL-cholesterol (r=−0.61, P=0.02) and apoB-100 (r=−0.54, P=0.04) concentrations. Fenofibrate improves endothelial dysfunction in statin-treated Type 2 diabetic patients. This may relate partly to enhanced reduction in LDL-cholesterol and apoB-100 concentrations.

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Abstract 1421: In Vivo Measurement of Flow-Mediated Vasodilation in Living Rats using High Resolution Ultrasound: Age-Dependent Endothelial Dysfunction

Circulation ◽

10.1161/circ.116.suppl_16.ii_292-b ◽

2007 ◽

Vol 116 (suppl_16) ◽

Author(s):

Christian Heiss ◽

Richard E Sievers ◽

Nicolas Amabile ◽

Tony Y Momma ◽

Shobha Natarajan ◽

...

Keyword(s):

High Resolution ◽

Endothelial Dysfunction ◽

Endothelial Function ◽

Femoral Artery ◽

Reactive Hyperemia ◽

Surrogate Marker ◽

Flow Measurements ◽

Age Related ◽

Age Dependent

In humans, endothelial function serves as a surrogate marker for cardiovascular health and is measured as changes in arterial diameter after temporary ischemia (flow-mediated dilation; FMD). We developed an FMD-related approach to study conduit artery vasodilation in living rats, and demonstrate a reduction in FMD in older versus younger animals consistent with age-related endothelial dysfunction. Diameter and Doppler-flow measurements were obtained from the femoral artery using high-resolution ultrasound (35 MHz). We observed dose-dependent vasodilation using both endothelium-dependent and endothelium-independent pharmacologic vasodilators (acetylcholine and nitroglycerine). Flow-dependent vasodilation was observed in response to flow increase induced both by adenosine and local saline infusion. Transient hindlimb ischemia led to reactive hyperemia with sequential flow velocity increase and femoral artery dilation, the latter of which was completely abolished by NO-synthase (NOS) inhibition with L-NMMA. To demonstrate its applicability in a model of endothelial dysfunction, we show that FMD is significantly reduced in older versus younger animals. While FMD was completely NOS-dependent in younger animals, NOS-dependent mechanisms accounted for only half of the FMD in older animals, with the remainder being blocked by charybdotoxin (CTx) and apamin suggesting contribution of endothelium-derived-hyperpolarizing-factor. Using this new integrative physiologic model to reproducibly study FMD in living rats, we show that age-dependent endothelial dysfunction is accompanied by a shift in mechanisms underlying vasodilatory endothelial function.

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Effects of Blackcurrant Anthocyanin on Endothelial Function and Peripheral Temperature in Young Smokers

Molecules ◽

10.3390/molecules24234295 ◽

2019 ◽

Vol 24 (23) ◽

pp. 4295 ◽

Cited By ~ 2

Author(s):

Toshiko Tomisawa ◽

Naoki Nanashima ◽

Maiko Kitajima ◽

Kasumi Mikami ◽

Shizuka Takamagi ◽

...

Keyword(s):

Endothelial Dysfunction ◽

Endothelial Function ◽

Skin Temperature ◽

Healthy Male ◽

Double Blind ◽

Beneficial Effects ◽

Flow Mediated Dilatation ◽

Young Smokers ◽

Peripheral Temperature ◽

Level 2

Background: Blackcurrant anthocyanin (BCA) is expected to repair endothelial dysfunction, but it remains unclear whether beneficial effects are present in young healthy persons. This study examines whether supplements containing blackcurrant anthocyanin improve endothelial function and peripheral temperature in young smokers. Methods: Young, healthy male nonsmokers (N group: n = 11; mean age 22 ± 2 years) and smokers (S group: n = 13; mean age 21 ± 1 years) were enrolled. A randomized and double-blind trial was designed to compare the effects of no supplement, a supplement containing 50 mg of blackcurrant anthocyanin (supplement A), and a supplement containing 50 mg of blackcurrant anthocyanin plus vitamin E (supplement B) on flow-mediated dilatation (FMD) and skin temperature. Results: Under no supplement, FMD was unchanged during the 2 h period after smoking in the N group, whereas it was decreased during the 2 h period after smoking in the S group. Under the A supplement, FMD was decreased 1 h after smoking and returned to the baseline level 2 h after smoking in the S group. The skin temperature in the area of the foot dorsum was decreased in the S group after smoking compared with that in the N group, who did not smoke, whereas under A and B supplements, it was higher in the S group compared with that in the N group. Conclusions: BCA could attenuate the smoking-induced acute endothelial dysfunction and improve peripheral temperature in young smokers.

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Supplementation with Hydroxytyrosol and Punicalagin Improves Early Atherosclerosis Markers Involved in the Asymptomatic Phase of Atherosclerosis in the Adult Population: A Randomized, Placebo-Controlled, Crossover Trial

Nutrients ◽

10.3390/nu11030640 ◽

2019 ◽

Vol 11 (3) ◽

pp. 640 ◽

Cited By ~ 5

Author(s):

Rebeca Quirós-Fernández ◽

Bricia López-Plaza ◽

Laura Bermejo ◽

Samara Palma-Milla ◽

Carmen Gómez-Candela

Keyword(s):

Blood Pressure ◽

Endothelial Dysfunction ◽

Endothelial Function ◽

Crossover Trial ◽

Adult Population ◽

Oral Supplementation ◽

Flow Mediated Dilatation ◽

Asymptomatic Phase ◽

Double Blinded ◽

Early Atherosclerosis

Hydroxytyrosol (HT) and Punicalagin (PC) exert cardioprotective and anti-atherosclerotic effects. This study evaluates the effect of oral supplementation with HT and PC (SAx) on early atherosclerosis markers in middle-aged, seemingly healthy adults. A randomized, double-blinded, placebo-controlled, crossover trial was performed for 20 weeks. There were two treatment sequences (Placebo/SAx, n = 41; SAx/Placebo, n = 43) for which the intervention periods (Placebo and SAx) were 8 weeks long, followed by a 4-week wash out period. The supplement was composed of 9.9 mg of HT and 195 mg of PC, and the placebo was composed of maltodextrin. SAx increased endothelial function (Flow-mediated dilatation [FMD]: 2.36%; p < 0.001) in the endothelial dysfunction subgroup compared to the placebo (2.36 ± 3.9 vs. 0.76 ± 3.5%, p < 0.05). SAx also reduced oxLDL by −28.74 ng/mL (p < 0.05) in subjects with higher levels of oxLDL, which was an improvement compared with the placebo (−28.74 ± 40.2 vs. 25.64 ± 93.8 ng/mL, p < 0.001). The prehypertension and hypertension subgroups exhibited decreased systolic (−15.75 ± 9.9 mmHg; p < 0.001) and diastolic (−6.36 ± 8.7 mmHg; p < 0.001) blood pressure after SAx consumption. Moreover, the systolic prehypertension and hypertension subgroups presented significant differences in systolic blood pressure compared to the placebo (−15.75 ± 9.9 vs. −2.67 ± 12.0 mmHg, p < 0.05). In conclusion, the supplement exerted anti-atherosclerotic effects by improving endothelial function, blood pressure, and levels of circulating oxLDL, especially for persons in whom these parameters were altered.

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Flow-Mediated Dilatation of the Brachial Artery for Assessing Endothelial Dysfunction in Children with Moyamoya Disease

Pediatric Neurosurgery ◽

10.1159/000509406 ◽

2020 ◽

Vol 55 (3) ◽

pp. 149-154

Author(s):

Eun-Hee Kim ◽

Hyung-Chul Lee ◽

Jaeyeon Chung ◽

Sang-Hwan Ji ◽

Young-Eun Jang ◽

...

Keyword(s):

Endothelial Dysfunction ◽

Moyamoya Disease ◽

Brachial Artery ◽

Flow Mediated Dilatation

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Endothelial dysfunction is an independent factor responsible for vasospastic angina

Clinical Science ◽

10.1042/cs1010707 ◽

2001 ◽

Vol 101 (6) ◽

pp. 707-713 ◽

Cited By ~ 17

Author(s):

Hiroki TERAGAWA ◽

Masaya KATO ◽

Junichi KUROKAWA ◽

Togo YAMAGATA ◽

Hideo MATSUURA ◽

...

Keyword(s):

Endothelial Dysfunction ◽

Endothelial Function ◽

Brachial Artery ◽

Coronary Stenosis ◽

Intima Media Thickness ◽

Control Group ◽

Test Results ◽

Independent Factor ◽

Atherosclerotic Changes ◽

Significant Coronary Stenosis

In order to evaluate peripheral endothelial function in patients with vasospastic angina (VSA), we measured flow-mediated dilation (FMD) of the brachial artery in patients with VSA and compared it with FMD in patients without VSA. Endothelial dysfunction is considered one of the mechanisms underlying VSA. However, its exact role remains to be clarified. The study included 30 patients with positive spasm-provocational test results without evidence of significant coronary stenosis (VSA group) and 30 patients with negative spasm-provocational test results without evidence of significant coronary stenosis (control group). In each patient, brachial artery diameter responses to hyperemic flow and glyceryl trinitrate spray were measured using high-resolution ultrasound. The carotid intima-media thickness was also measured as a marker of systemic atherosclerosis. FMD was lower in the VSA group (4.8±0.5%) compared with the control group (9.4±0.7%, P < 0.0001). In the VSA group, FMD was not affected by coronary risk factors or the presence of atherosclerotic changes on coronary angiography. Glyceryl trinitrate-induced dilation did not differ between the two groups. The intima-media thickness was comparable between the VSA (0.85±0.04mm) and control groups (0.81±0.05mm). These findings indicated that peripheral endothelial function is impaired only in the VSA group, whereas the atherosclerotic changes were similar in the two groups. We conclude that endothelial dysfunction may be an independent factor responsible for the development of VSA.

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Peripheral Arterial Stiffness and Endothelial Dysfunction in Idiopathic and Scleroderma Associated Pulmonary Arterial Hypertension

The Journal of Rheumatology ◽

10.3899/jrheum.081088 ◽

2009 ◽

Vol 36 (5) ◽

pp. 970-975 ◽

Cited By ~ 44

Author(s):

NIR PELED ◽

DAVID SHITRIT ◽

BENJAMIN D. FOX ◽

DEKEL SHLOMI ◽

ANAT AMITAL ◽

...

Keyword(s):

Pulmonary Arterial Hypertension ◽

Endothelial Dysfunction ◽

Arterial Stiffness ◽

Endothelial Function ◽

Arterial Hypertension ◽

Systolic Pressure ◽

Vascular Involvement ◽

Pulmonary Pressure ◽

Pulmonary Arterial ◽

Peripheral Arterial

Objective.Pulmonary endothelial dysfunction and increased reflection of pulmonary pressure waves have been reported in pulmonary arterial hypertension (PAH). However, the systemic vascular involvement is not fully understood. Our study focused on the systemic arterial stiffness and endothelial involvement in idiopathic and scleroderma associated PAH.Methods.Peripheral arterial stiffness and endothelial function were evaluated in 38 patients with idiopathic (n = 28) and scleroderma associated (n = 10) PAH, and 21 control subjects (13 healthy; 8 with scleroderma and normal pulmonary pressure). All participants underwent clinical and cardiopulmonary evaluation. Arterial stiffness was measured through the fingertip tonometry derived augmentation index (AI), which is the boost increase in the late systolic pressure wave after the initial systolic shoulder. Endothelial function was measured by forearm blood flow dilatation response to brachial artery occlusion by a noninvasive plethysmograph (EndoPAT 2000), which is associated with nitric oxide-dependent vasodilatation and yields a peripheral arterial tone (PAT) ratio.Results.Mean systolic pulmonary pressure was 70.5 ± 21.6 mm Hg (idiopathic-PAH) and 69.3 ± 20 mm Hg (scleroderma-PAH). AI was higher in scleroderma patients (10.5% ± 19.6% in healthy controls, 9.0% ± 21.5% in idiopathic-PAH, 20.1% ± 19.1% in scleroderma-PAH, and 24.4% ± 18.9% in scleroderma-controls; nonsignificant). PAT ratio was significantly lower (p < 0.05) than control values in idiopathic-PAH and scleroderma-PAH (PAT ratio: control 2.20 ± 0.25; idiopathic 1.84 ± 0.51; scleroderma 1.66 ± 0.66). AI was not correlated to endothelial dysfunction. There were no differences between the 2 PAH patient groups in age, body mass index, New York Heart Association classification, or 6-min walk test.Conclusion.Our study shows a trend towards increased arterial stiffness in scleroderma (nonsignificant), and also peripheral endothelial dysfunction in idiopathic-PAH and in scleroderma-PAH. These findings suggest involvement of different vessels in scleroderma-PAH compared to idiopathic-PAH.

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