Hyperhomocysteinaemia in young adults is not associated with impaired endothelial function

2000 ◽  
Vol 100 (1) ◽  
pp. 67-72 ◽  
Author(s):  
Colm G. HANRATTY ◽  
Daniel F. MCAULEY ◽  
Lawrence T. MCGRATH ◽  
Ian S. YOUNG ◽  
G. Dennis JOHNSTON
Keyword(s):  
Blood Flow ◽  
Endothelial Dysfunction ◽  
Endothelial Function ◽  
Vascular Disease ◽  
Prolonged Exposure ◽  
Forearm Blood Flow ◽  
Control Group ◽  
Atherosclerotic Vascular Disease ◽  
Homocysteine Concentration ◽  
Mild Hyperhomocysteinaemia

A mild to moderate elevation of the total homocysteine concentration (tHcy) is now recognized as a risk factor for vascular disease. It is also associated with endothelial dysfunction in middle-aged and elderly individuals without overt atherosclerotic vascular disease. This is important, as endothelial dysfunction is a well recognized early and potentially reversible marker of the atherosclerotic process. We investigated whether mild hyperhomocysteinaemia was associated with endothelial dysfunction in otherwise healthy young males. We compared endothelial function, by measuring forearm blood flow, in 17 males with mild hyperhomocysteinaemia (defined as tHcy > 10 µmol/l) and 14 controls with low tHcy (defined as < 5 µmol/l). Forearm blood flow was measured in response to the intra-arterial infusion of acetylcholine (endothelial-dependent response) or sodium nitroprusside (endothelial-independent response). Responses to the vasoactive substances were expressed as the area under the curve of the change in forearm blood flow from baseline. Data are given as mean (95% confidence interval). The two groups were well matched for age, body mass index, pulse rate and blood pressure. tHcy was significantly different between the groups [12.3 (10.4–14.2) µmol/l compared with 4.9 (4.6–5.1) µmol/l; P < 0.001]. Concentrations of vitamin B12 and folate were significantly higher in the control group. There was no difference in basal forearm blood flow between the group with mild hyperhomocysteinaemia and the controls, and both the endothelial-dependent [37.5 (26.2–38.8) and 35.3 (26.1–44.4) arbitrary units respectively] and -independent [26.1 (22.2–29.9) and 25.9 (21.0–30.8) units respectively] responses were not significantly different between the groups. Thus the present study demonstrates that, in healthy adults, mild elevation of tHcy was not associated with impaired endothelial-dependent vasodilation. These data suggest an age effect with regard to homocysteine and endothelial dysfunction. The development of vascular disease in individuals with hyperhomocysteinaemia may only result with higher concentrations or after prolonged exposure.

Effect of Estrogen Replacement Therapy on Endothelial Function of Peripheral Resistance Artery in Postmenopausal Women - Comparison of Normotensive Subjects and Hypertensive Patients -

Hypertension ◽  
2000 ◽  
Vol 36 (suppl_1) ◽  
pp. 713-713
Author(s):  
Yukihito Higashi ◽  
Mitsuhiro Sanada ◽  
Shota Sasaki ◽  
Keigo Nakagawa ◽  
Koso Ohama ◽  
...  
Keyword(s):  
Blood Flow ◽  
Endothelial Dysfunction ◽  
Endothelial Function ◽  
Replacement Therapy ◽  
Postmenopausal Women ◽  
Estrogen Replacement Therapy ◽  
Forearm Blood Flow ◽  
Reactive Hyperemia ◽  
Sublingual Nitroglycerin ◽  
Estrogen Replacement

P112 To determine whether endothelial dysfunction is demonstrable in the forearm circulation of hypertensive postmenopausal women (HPW) compared with normotensive postmenopausal women (NPW), and to evaluate the effects of long-term estrogen replacement therapy (ERT) on endothelial function in the HPW and NPW, we randomized both HPW and NPW into groups with ERT for 12 weeks (n=26 and 10) or with placebo (n=8 and 6), respectively. Forearm blood flow was measured using strain-gauge plethysmography during reactive hyperemia to test endothelium-dependent vasodilation, and after sublingual nitroglycerin administration to test endothelium-independent vasodilation. Basal forearm blood flow was similar in NPW and HPW. Forearm blood flow in HPW during reactive hyperemia was significantly less than that in NPW. Increases in forearm blood flow after nitroglycerin were similar in the two groups. ERT lowered LDL cholesterol and increased estradiol and HDL cholesterol; no change occurred in the placebo group. Changes in these parameters evoked by ERT were similar in HPW and NPW. Basal blood pressures, heart rate, forearm blood flow, or body weight was not changed by ERT. After 12 weeks of ERT, maximal forearm blood flow response during reactive hyperemia increased significantly from 18.4 ± 2.6 to 28.6 ± 3.4 mL/min/100 mL tissue (p<.05) in HPW and from 26.5 ± 1.9 to 30.9 ± 3.9 mL/min/100 mL tissue (p<.05) in NPW, but it was not changed by placebo. The improvement of reactive hyperemia after ERT was significantly greater in HPW than in NPW (56 ± 8 vs. 17 ± 3%, P<.05). Changes in forearm blood flow after sublingual nitroglycerin administration were similar before and after 12 weeks of ERT. These findings suggest that continued ERT improves endothelial dysfunction in postmenopausal women, and that HPW show endothelial dysfunction which can be improved by ERT via the mechanism other than beneficial effects on lipid metabolism.

Impaired cerebral CO2 vasoreactivity: association with endothelial dysfunction

2006 ◽  
Vol 291 (4) ◽  
pp. H1856-H1861 ◽  
Author(s):  
Shahar Lavi ◽  
Diana Gaitini ◽  
Victor Milloul ◽  
Giris Jacob
Keyword(s):  
Blood Pressure ◽  
Blood Flow ◽  
Endothelial Dysfunction ◽  
Endothelial Function ◽  
Sodium Nitroprusside ◽  
Forearm Blood Flow ◽  
Reactive Hyperemia ◽  
Area Under The Curve ◽  
Healthy Controls ◽  
No Donor

Conflicting data exist on the role of nitric oxide (NO) in cerebral blood flow (CBF) autoregulation. Previous studies involving human and animal subjects seem to indicate that NO involvement is limited to the CO2-dependent mechanism (chemoregulation) and not to the pressure-dependent autoregulation (mechanoregulation). We tested this hypothesis in patients with impaired endothelial function compared with healthy controls. Blood pressure, heart rate, end-tidal Pco2, CBF velocities (CBFV), forearm blood flow, and reactive hyperemia were assessed in 16 patients with diabetes mellitus and/or hypertension and compared with 12 age- and sex-matched healthy controls. Pressure-dependent autoregulation was determined by escalating doses of phenylephrine. CO2 vasoreactivity index was extrapolated from individual slopes of mean CBFV during normocapnia, hyperventilation, and CO2 inhalation. Measurements were repeated after sodium nitroprusside infusion. Indexes of endothelial function, maximal and area under the curve (AUC) of forearm blood flow (FBF) changes, were significantly impaired in patients (maximal flow: 488 ± 75 vs. 297 ± 31%; P = 0.01, AUC ΔFBF: 173 ± 17 vs. 127 ± 11; P = 0.03). Patients and controls showed similar changes in cerebrovascular resistance during blood pressure challenges (identical slopes). CO2 vasoreactivity was impaired in patients compared with controls: 1.19 ± 0.1 vs. 1.54 ± 0.1 cm·s−1·mmHg−1; P = 0.04. NO donor (sodium nitroprusside) offsets this disparity. These results suggest that patients with endothelial dysfunction have impaired CO2 vasoreactivity and preserved pressure-dependent autoregulation. This supports our hypothesis that NO is involved in CO2-dependent CBF regulation alone. CBFV chemoregulation could therefore be a surrogate of local cerebral endothelial function.

scholarly journals New-Onset Diabetes, Endothelial Dysfunction, and Cardiovascular Outcomes in Hypertensive Patients: An Illness-Event Model Analysis

Biomedicines ◽  
2021 ◽  
Vol 9 (7) ◽  
pp. 721
Author(s):  
Raffaele Maio ◽  
Edoardo Suraci ◽  
Benedetto Caroleo ◽  
Cristina Politi ◽  
Simona Gigliotti ◽  
...  
Keyword(s):  
Blood Flow ◽  
Endothelial Dysfunction ◽  
Confidence Interval ◽  
Cardiovascular Events ◽  
Forearm Blood Flow ◽  
Cardiovascular Outcomes ◽  
Hazard Ratio ◽  
Baseline Status ◽  
Event Model ◽  
New Onset

Background. Insulin resistance and endothelial dysfunction are common findings in hypertensives, both predisposing to a higher risk of diabetes and cardiovascular events. We designed this study to evaluate the role of endothelial dysfunction in three pathogenetic pathways: (1) from baseline to cardiovascular events, (2) from baseline to diabetes, and (3) from new-onset diabetes to cardiovascular events. Methods. We enrolled 653 Caucasian never-treated hypertensives. Endothelial dysfunction was investigated by strain-gauge plethysmography; incident diabetes and cardiovascular events were evaluated by an illness-event model analysis. Results. During the follow-up (median 113 months), we documented 191 new cardiovascular events and 92 new cases of diabetes. In a multiple Cox regression analysis, acetylcholine-stimulated forearm blood flow [100% decrease, hazard ratio: 2.42 (95% confidence interval = 1.72–3.40)] and serum high-sensitivity C-reactive protein [hazard ratio: 1.30 (95% confidence interval = 1.21–1.40)] had an independent association with cardiovascular outcomes. The incidence rate of cardiovascular outcomes in diabetes-developer patients was higher than in the diabetes-free ones (34.9 vs. 2.5 events per 100 persons-year). In an illness-event model, a 100% decrease in forearm blood flow was associated with a 55.5% hazard ratio increase (hazard ratio: 1.56, 95% confidence interval: 1.33–1.82) of transition 1 (from baseline status to cardiovascular events) and to an almost doubled increase (hazard ratio: 2.54, 95% CI: 2.00–3.25) of the risk of transition 2 (from baseline status to diabetes). No such effects were found in transition 3 (from diabetes to cardiovascular events). Conclusions. Endothelial dysfunction plays a primary role in the pathways leading to diabetes and cardiovascular events in hypertensives. When diabetes is overt, endothelial dysfunction has no predictive value for subsequent cardiovascular events.

Endothelial dysfunction is an independent factor responsible for vasospastic angina

2001 ◽  
Vol 101 (6) ◽  
pp. 707-713 ◽  
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.

Effect of Methionine Loading on 5-Methyltetrahydrofolate, S-Adenosylmethionine and S-Adenosylhomocysteine in Plasma of Healthy Humans

1996 ◽  
Vol 91 (1) ◽  
pp. 79-86 ◽  
Author(s):  
Franziska M. T. Loehrer ◽  
Walter E. Haefeli ◽  
Christian P. Angst ◽  
Garry Browne ◽  
Greta Frick ◽  
...  
Keyword(s):  
Vascular Disease ◽  
Active Form ◽  
Plasma Homocysteine ◽  
Methionine Metabolism ◽  
Fasting State ◽  
Homocysteine Concentration ◽  
Healthy Humans ◽  
The Relationship ◽  
Mild Hyperhomocysteinaemia ◽  
Expected Increase

1. Elevated plasma homocysteine concentration, either in the fasting state or after methionine loading, is an independent risk factor for vascular disease in man. Methionine loading has been used to investigate impaired methionine metabolism, especially of the trans-sulphuration pathway, but most studies have focused on changes in homocysteine. 2. We investigated the effect of methionine excess on total plasma homocysteine, 5-methyltetrahydrofolate (which is the active form of folate in the remethylation of homocysteine to methionine), S-adenosylmethionine (the first metabolite of methionine) and S-adenosylhomocysteine (the demethylated product of S-adenosylmethionine) over 24 h in 12 healthy subjects. 3. As well as the expected increase in homocysteine (from 8.0 ± 1.3 to 32.6 ± 10.3 μmol/l, mean ± SD, P > 0.001), S-adenosylmethionine showed a significant transient increase (from 37.9 ± 25.0 to 240.3 ± 109.2 nmol/l, P > 0.001), which correlated well with homocysteine (r2 = 0.92, P > 0.001). 5-Methyltetrahydrofolate values decreased significantly (from 23.2 ± 7.2 to 13.1 ± 2.9 nmol/l, P > 0.01), and gradually returned to baseline levels after 24 h. No significant change over the time of measurement was found for S-adenosylhomocysteine. 4. The sequence of metabolic changes observed in this study strongly suggests that a change in either homocysteine or S-adenosylmethionine may cause a reduction in 5-methyltetrahydrofolate. This must be considered in evaluating the relationship between folate and homocysteine in vascular disease. The metabolic relationships illustrated in this study should be evaluated in the search for pathogenetic mechanisms of mild hyperhomocysteinaemia and vascular disease.

scholarly journals PO-087 4-weeks hypoxia (HHL) training improves rowers’ cutaneous microcirculation

2018 ◽  
Vol 1 (3) ◽  
Author(s):  
Zhijun Meng ◽  
Binghong Gao
Keyword(s):  
Blood Flow ◽  
Endothelial Function ◽  
Forearm Blood Flow ◽  
Early Stage ◽  
Reactive Hyperemia ◽  
Peripheral Circulation ◽  
Reserve Capacity ◽  
Hypoxic Training ◽  
Cutaneous Microcirculation ◽  
Traditional Research

Objective Sport scientists always pay attention to cardiorespiratory and hematologic system on benefit of hypoxic training, but peripheral circulation may be one of these benefit, which is one cause of improving performance. So, in order to know whether or not hypoxic training affect athletes’ cutaneous microcirculation, we test rowers’ microcirculation for 4 weeks’ High Live-High Train-Low exercise(HHL). Methods The subject is 21 male rowers of Shanghai rowing team.12 of them take part in 4 weeks HHL (train and live at 2500m, exercise at 100m), while 9 of them train in normoxia. Forearm and leg cutaneous blood flow(CBF) was measured using a laser doppler flowmeter (PeriFlux600, Perimed, Sweden) at room temperature (22℃) with subject lying position and after testing in that position for at least 10min. We tested the forearm and leg blood flow, and also the blood flow when localized heating to 44℃ for 3 mins. Microvascular reactivity(MVR) was evaluated form the maximal post occlusive reactive hyperemia(PORH) following 3-min forearm ischemia produced by cuff inflation (200mm Hg). Similar procedures have been used by other investigators. Blood pressure was measured by brachial auscultation. SPO2 and heart rate was measured by a hand hold pulse oximeter (NONIN, 9500, USA) .The blood flow was measured 4 times, baseline, 1stweek, 3rdweek and post. Results Blood flow and CMBC of forearm of HHL increased significantly at 1stweek(8.9,13.0;112.0,151.0,P<0.05), but thigh and NOM group did not increase. The lowest and highest blood flow of PORH both increase at 1stweek(2,9,3.2;46.0,53.0;0.05<P<0.1). At 3rdweek, HHL group’s resting blood flow and CMBC of forearm is lower than 1stweek(9.3,13.0;124.5,151.0), but higher than pretraining, but velocity of blood flow decreased(8.2,9.2).  These results suggest at early stage of HHL, vasoconstriction may be dominant. But when rowers suffer more and more hypoxia, vasodilation and angiogenesis may play a key role in their skin blood flow. At 3rdweek after training, the blood flow and CMBC are similar with baseline. Conclusions 4 weeks HHL training of rowers increase forearm blood flow, but no thigh. This is because thigh is main working muscle of rowers, which may be affected by training status and fatigue. And also, PORH reserve capacity is an indicator of endothelial function. In this study, we find HHL rowers increase their PORH reserve capacity, which means endothelial function is improved by hypoxia training. So, besides the traditional research of Hematologic System on hypoxia training, we find 4 weeks HHL training increase forearm blood flow and improve endothelial function. This may be one mechanism of improving performance, which need more studies to confirm.

scholarly journals Endothelial Dysfunction: Is There a Hyperglycemia-Induced Imbalance of NOX and NOS?

2019 ◽  
Vol 20 (15) ◽  
pp. 3775 ◽  
Author(s):  
Cesar A. Meza ◽  
Justin D. La Favor ◽  
Do-Houn Kim ◽  
Robert C. Hickner
Keyword(s):  
Type 2 Diabetes ◽  
Cardiovascular Disease ◽  
Blood Flow ◽  
Endothelial Dysfunction ◽  
Endothelial Function ◽  
Vascular Dysfunction ◽  
Vascular Complications ◽  
Enzymatic Production

NADPH oxidases (NOX) are enzyme complexes that have received much attention as key molecules in the development of vascular dysfunction. NOX have the primary function of generating reactive oxygen species (ROS), and are considered the main source of ROS production in endothelial cells. The endothelium is a thin monolayer that lines the inner surface of blood vessels, acting as a secretory organ to maintain homeostasis of blood flow. The enzymatic production of nitric oxide (NO) by endothelial NO synthase (eNOS) is critical in mediating endothelial function, and oxidative stress can cause dysregulation of eNOS and endothelial dysfunction. Insulin is a stimulus for increases in blood flow and endothelium-dependent vasodilation. However, cardiovascular disease and type 2 diabetes are characterized by poor control of the endothelial cell redox environment, with a shift toward overproduction of ROS by NOX. Studies in models of type 2 diabetes demonstrate that aberrant NOX activation contributes to uncoupling of eNOS and endothelial dysfunction. It is well-established that endothelial dysfunction precedes the onset of cardiovascular disease, therefore NOX are important molecular links between type 2 diabetes and vascular complications. The aim of the current review is to describe the normal, healthy physiological mechanisms involved in endothelial function, and highlight the central role of NOX in mediating endothelial dysfunction when glucose homeostasis is impaired.

L-Arginine protects from ischemia-reperfusion-induced endothelial dysfunction in humans in vivo

2003 ◽  
Vol 95 (6) ◽  
pp. 2218-2222 ◽  
Author(s):  
John Pernow ◽  
Felix Böhm ◽  
Emma Beltran ◽  
Adrian Gonon
Keyword(s):  
Blood Flow ◽  
Endothelial Dysfunction ◽  
Reperfusion Injury ◽  
Forearm Blood Flow ◽  
Ischemia Reperfusion Injury ◽  
Ischemia Reperfusion ◽  
Venous Occlusion ◽  
Myocardial Ischemia Reperfusion Injury ◽  
Myocardial Ischemia Reperfusion

It has been shown that nitric oxide (NO) protects from myocardial ischemia-reperfusion injury in animal models. The present study investigated whether administration of the NO substrate l-arginine protects against ischemia-reperfusion-induced endothelial dysfunction in humans. Forearm blood flow was measured with venous occlusion plethysmography in 16 healthy male subjects who were investigated on two occasions. Forearm ischemia was induced for 20 min followed by 60-min reperfusion. With the use of a crossover protocol, the subject received a 15-min intrabrachial artery infusion of l-arginine (20 mg/min) and vehicle (saline, n = 12 or d-arginine, n = 4) starting at 15 min of ischemia on two separate occasions. Compared with preischemia, endothelium-dependent increase in forearm blood flow induced by intra-arterial acetylcholine (3–30 μg/min) was significantly impaired at 15 and 30 min of reperfusion when the subjects received saline ( P < 0.001). When the subjects received l-arginine, the acetylcholine-induced increase in forearm blood flow was not significantly affected by ischemia-reperfusion. The recovery of endothelium-dependent vasodilatation at 15- and 30-min reperfusion was significantly greater after administration of l-arginine than after saline ( P < 0.05). d-Arginine did not affect the response to acetylcholine. Endothelium-independent vasodilatation to nitroprusside was not affected during reperfusion. These results demonstrate that the NO substrate l-arginine significantly attenuates ischemia-reperfusion-induced endothelial dysfunction in humans in vivo. This suggests that l-arginine may be useful as a therapeutic agent in the treatment of ischemia-reperfusion injury in humans.

Features of chorioretinal hemodynamics against the background of correction of endothelial dysfunction in women after preeclampsia

2021 ◽  
pp. 325-329
Author(s):  
О.V. Kolenko ◽  
◽  
Е.L. Sorokin ◽  
А.А. Fil ◽  
◽  
...  
Keyword(s):  
At Risk ◽  
Blood Flow ◽  
Endothelial Dysfunction ◽  
Prophylactic Treatment ◽  
Prediction Algorithm ◽  
Control Group ◽  
Hemodynamic Parameters ◽  
Retinal Pathology

Purpose. To assess the clinical efficacy of drug correction of endothelial dysfunction in women at risk using the study of chorioretinal hemodynamic parameters. Material and methods. Using the prediction algorithm developed by us, 60 women were selected at risk of developing vascular retinal pathology. All women were divided into two subgroups. 1st group – 30 patients who underwent courses of drug correction of endothelial dysfunction; 2nd group included 30 women who did not receive courses of prophylactic treatment. The control group was represented by 30 women who underwent physiological pregnancy. The entire population of women underwent a study of the parameters of chorioretinal hemodynamics. Results. By the end of the follow-up period (3–4.5 years) in the 1st group there was a statistically significant improvement in the parameters of chorioretinal hemodynamics in comparison with both the 2nd group in the period 3 years after childbirth, and with the indicators of the 1st group after 6–8 months after childbirth. Conclusion. It can be argued that in the group of women who underwent long-term drug correction of endothelial dysfunction, there was a statistically significant improvement in a number of indicators of chorioretinal hemodynamics compared with women who did not receive prophylactic treatment (p<0.01). Key words: chorioretinal hemodynamics, macular blood flow, linear blood flow velocity, preeclampsia, endothelial dysfunction, drug correction of endothelial dysfunction.

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