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Results for “Endothelial function”

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PubMed1994

Effect of L-arginine on coronary endothelial function in cardiac transplant recipients. Relation to vessel wall morphology.

BACKGROUND: Coronary endothelial vasodilator dysfunction is a common finding in cardiac transplant recipients and may represent an early marker for the development of intimal thickening and graft atherosclerosis. The present study tested the hypothesis that endothelial dysfunction precedes intimal thickening and that administration of L-arginine, the precursor of endothelium-derived relaxing factor, improves endothelial vasodilator function of coronary conduit and resistance vessels if given at an early stage of graft atherosclerosis. METHODS AND RESULTS: Acetylcholine (10(-6), 10(-5), 10(-4) mol/L) was infused into the left anterior descending or circumflex artery and repeated after intravenous infusion of L-arginine (10 mg.kg-1.min-1 over 20 minutes) in 18 cardiac transplant recipients. Epicardial responses were evaluated by quantitative angiography, and the microcirculation was studied by determination of coronary blood flow with a Doppler flow velocity wire. Intimal thickening was assessed by intravascular ultrasound (n = 14). In epicardial coronary arteries, acetylcholine tended to elicit vasoconstriction. Epicardial coronary vasoconstriction elicited by acetylcholine was attenuated by infusion of L-arginine (10(-4) mol/L, -6.8% versus -2.8%; P < .01); this beneficial effect was observed predominantly in patients with normal intravascular ultrasound characteristics. In coronary resistance vessels, acetylcholine induced vasodilation, reflected by increases in coronary blood flow. The acetylcholine-induced increase in blood flow was significantly enhanced with L-arginine (at a dose of 10(-4) mol/L, + 121% versus 176%; before versus after L-arginine, P < .002). CONCLUSIONS: The coronary vasculature of cardiac transplant recipients exhibits a generalized endothelial dysfunction of conduit and resistance vessels. L-Arginine improves endothelial dysfunction of both coronary microvasculature and epicardial coronary arteries. The reversibility of epicardial endothelial dysfunction by L-arginine is more likely in vessels with normal wall morphology.

Acetylcholine↗

PubMed1994

Effect of chronic ANG I-converting enzyme inhibition on aging processes. III. Endothelial function of mesenteric arterial bed of rat.

Age-related changes in endothelial (E) function were studied in mesenteric arterial bed (MAB) preparations removed from male, normotensive, WAG/Rij rats. At the age of 6 mo, one-half of the animals was assigned to chronic treatment with a hypotensive dose of an angiotensin I (ANG I)-converting enzyme inhibitor (ACEI; perindopril, 1 mg.kg-1.day-1 po). Animals were killed at 6, 12, 24, or 30 mo of age; the MAB was perfused in vitro, perfusion pressure (PP) being taken as an index of arteriolar tone. Disruption of E function produced a fall in baseline PP in all groups except 30-mo-old rats, suggesting that 1) baseline tone is maintained by the release of E vasoconstrictor factor(s) and 2) this mechanism is impaired in 30-mo-old rats. The muscarinic agonist, carbachol, antagonized vasoconstriction produced by norepinephrine (NE) in the presence of E. This mechanism was impaired in 30-mo-old rats. NE vasoconstriction increased following disruption of E, suggesting that NE release of endothelium-derived relaxing factor attenuates vasoconstriction. This mechanism was impaired in 30-mo-old rats. Chronic ACEI postponed the age-related decrease in E function, possibly due to a direct effect, or an indirect effect via the prolonged hypotensive action of such treatment.

Aging↗

PubMed2001

Use of measures of endothelial function to stratify risk.

Measures of endothelial dysfunction can be used to stratify risk in coronary artery disease and diabetes. Two studies are reviewed in which endothelial dysfunction was shown to be associated with an increased risk of cardiovascular events and to predict long term atherosclerotic disease. A study that showed reduced microvascular and macrovascular reactivity in subjects at risk for type 2 diabetes, and a study indicating that endothelial dysfunction precedes the development of microalbuminuria in type 1 diabetes are reviewed.

Coronary Disease↗

PubMed1992

Cytokine regulation of endothelial cell function.

Endothelial cells have long been viewed as a passive lining of blood vessels endowed essentially with negative properties such as that of being nonreactive to blood components. It is now evident that upon exposure to environmental signals, cytokines in particular, vascular cells undergo profound changes in gene expression and function that allow these cells to participate actively in inflammatory reactions, immunity, and thrombosis. Different mediators (e.g., interleukin-1 [IL-1] and interferon-gamma) activate relatively distinct sets of functions. These functional programs expressed in activated endothelial cells include the production by the same cells of cytokines (e.g., IL-1, IL-6, chemotactic cytokines, and colony-stimulating factors), which regulate hematopoiesis, the differentiation and proliferation of T and B lymphocytes, and the extravasation of leukocytes. The identification of cytokine circuits through which vascular cells participate to thrombotic, inflammatory, and immune reactions provides novel targets for therapeutic intervention.

Animals↗

PubMedDate not supplied

Endothelial function and coronary risk reduction: mechanisms and influences of nitric oxide.

The biological mechanisms related to progression and regression of CAD are indeed complex. While endothelial injury and lipid accumulation play an important role in the progression/regression of CAD, mechanisms of vascular function, particularly that of the endothelial modulation of vasodilation, cannot be ignored. Much is yet to be learned about the influences of endothelial function on the progression/regression and stabilization of CAD. Initial evidence suggesting that risk reduction interventions favorably influence vascular function argues for further investigation of this role. To date, much of the research on risk reduction has focused on lipid lowering and regression of artery plaque, a focus on artery structure. A focus on both function and structure is likely to expand our understanding of the effect of risk reduction interventions beyond lipid lowering. Given the multifactorial causes associated with development of CAD, such an approach is necessary.

Coronary Disease↗

PubMed2002

[Tissue insulin resistance and endothelial function of large vessels in patients with arterial hypertension].

AIM: To examine insulin resistance and hyperinsulinemia in obese patients with moderate arterial hypertension (AH) without diabetes mellitus, glucose intolerance, and ischemic heart disease; to evaluate the endothelial vasomotor function of large vessels. MATERIAL AND METHODS: 41 males (mean age 49.3 +/- 5.4 years) with AH were examined by anthropometry, measurements of the levels of glucose, immunoreactive insulin, C-peptide, and biochemical blood tests. Endothelial vasomotor function was assessed ultrasonically. RESULTS: Insulin resistance preceding abnormal glucose tolerance was found in 52.4% of the patients with AH and obesity. In these patients lipid metabolic disturbances were more pronounced than in those without hyperinsulinemia. There was endothelial vasomotor dysfunction with preserved capacity of arteriolar and capillary walls for vasodilatation irrespective of the presence or absence of insulin resistance. CONCLUSION: Insulin resistance and endothelial dysfunction are most common in hypertensive patients with obesity.

Adult↗

PubMed2005

S-adenosylmethionine and 5-methyltetrahydrofolate are associated with endothelial function after controlling for confounding by homocysteine: the Hoorn Study.

OBJECTIVE: To explore to what extent homocysteine, S-adenosylmethionine (SAM), S-adenosylhomocysteine, total folate, 5-methyltetrahydrofolate (5-MTHF), vitamin B12, and vitamin B6 are associated with endothelium-dependent, flow-mediated vasodilation (FMD), and whether these associations are stronger in individuals with diabetes or other cardiovascular risk factors. METHODS AND RESULTS: In this population-based study of 608 elderly people, FMD and endothelium-independent nitroglycerin-mediated dilation (NMD) were ultrasonically estimated from the brachial artery (absolute change in diameter [mum]). High SAM and low 5-MTHF were significantly associated with high and low FMD, respectively (linear regression coefficient, [95% confidence interval]): 48.57 microm (21.16; 75.98) and -32.15 microm (-59.09; -5.20), but high homocysteine was not (-15.11 microm (-42.99; 12.78). High SAM and low 5-MTHF were also significantly associated with high and low NMD, respectively. NMD explained the association of 5-MTHF with FMD but not of SAM. No interactions were observed for diabetes or cardiovascular risk factors. CONCLUSIONS: In this elderly population, both SAM and 5-MTHF are associated with endothelial and smooth muscle cell function. The effect of homocysteine on endothelial function is relatively small compared with SAM and 5-MTHF. The relative impact of SAM, 5-MTHF, and homocysteine, and the mechanisms through which these moieties may affect endothelial and smooth muscle cell function need clarification.

Aged↗

PubMed2006

The nonlipid effects of statins on endothelial function.

Hydroxymethylglutaryl-coenzyme A reductase inhibitors or statins constitute one of the wonder drugs of the last 2 decades. Use of this hypolipidemic medication class reduces morbidity and mortality in patients with a wide variety of cholesterol levels. Beneficial effects of the medication are seen in advance of changes in lipids suggesting nonlipid mechanisms may play a role in mediating these benefits of statins. One important nonlipid mechanism by which statins may improve vascular outcomes is restoration of normal endothelial cell function. This review will discuss the nonlipid effects of statins on endothelial cell function to highlight other avenues of benefit conferred by these medications.

Cholesterol, LDL↗

PubMed1996

[Effect of vitamin E on the endothelial function of the regenerated aorta in rats following direct arterial injury].

Fibromuscular intimal injury is frequent after coronary or peripheral angioplasty. Peroxidation of circulating and membrane lipids have been implicated in intimal hyperplasia and endothelial dysfunction following direct arterial trauma. The aim of this study was to evaluate the effects of natural membrane antioxidant, vitamin E (VE), on the vascular reactivity of the regenerated endothelium. A first group of rats (n = 10) was pretreated with VE 100 IU/kg/day for a week before undergoing aortic (thoracic) endothelial denudation with a Fogarty catheter. Rats were then fed with the same VE supplemented diet for a 2-month period. A second group (n = 10), was similarly denudated and fed with soya oil (SO), VE vehicle, for the same period. A third group (n = 10) was denuded and used as control (CL). Endothelial-dependent and independent relaxations were assessed in organ chambers with acetylcholine (ACH), adenosine diphosphate (ADP), histamine (HIS), 5-hydroxytryptamine (5-HT) and sodium nitroprusside (SNP). Endothelial regeneration was evaluated with Evans blue staining. Vascular relaxation to SNP was not affected either by the regeneration process or the VE supplementation. However, endothelial-dependent relaxation to ACH and HIS were significantly impeded in the regenerated endothelium compared to control but was not influenced by the VE or the SO supplementation. Vascular contraction to 5-HT was significantly decreased in VE group compared to the other groups. Morphometric studies with Evans blue staining showed over 95% regeneration of the endothelial surface of the denuded aortas. Our results suggest that in spite of a complete anatomical regeneration, endothelial cells did not resume predenudation function. Endothelial-independent relaxation was preserved in all groups indicating that smooth muscle function was not altered by the regenerating process. The presence of dietary supplement of VE (up to 20 fold the daily requirement) did not prevent the endothelial dysfunction to ACH and HIS but attenuated the vaso-contraction to 5-HT and then could contribute to decreased vascular tone in endothelium-regenerated vessels.

Animals↗

PubMed2001

Impaired endothelial function in isolated human uremic resistance arteries.

BACKGROUND: Patients with chronic renal failure (CRF) face a markedly increased risk of cardiovascular death. CRF is frequently complicated by hypertension and changes in both the heart (left ventricular hypertrophy) and the vasculature (endothelial dysfunction and accelerated atherosclerosis). The mechanisms underlying changes in vascular function and specifically endothelial dysfunction are unclear. This present study therefore examined subcutaneous resistance artery function in vitro, comparing adult uremic patients and controls using wire myography. METHODS: Subcutaneous fat biopsies were obtained from 12 patients with CRF (median serum creatinine 735 micromol/L) at the time of renal transplantation or peritoneal dialysis catheter insertion, and from eight controls without renal disease at the time of abdominal surgery. Resistance arteries were mounted on a wire myograph. Their contractile ability was tested with high potassium depolarization, and endothelial integrity was tested by relaxation to acetylcholine. Cumulative concentration-response curves were then constructed for norepinephrine, endothelin-1, acetylcholine, and sodium nitroprusside (SNP). RESULTS: Following preconstriction with norepinephrine, vessels from uremic patients vasodilated less well to acetylcholine compared with vessels from controls [maximum % relaxation 77% (range 41, 97) vs. 98% (78, 100), P < 0.001]. The vasodilation to SNP was similar [95% (63, 100) vs. 94% (71, 100), P = 0.751]. There was a trend toward increased maximum pressure (kPa) achieved with both norepinephrine and endothelin-1 in vessels from uremic patients, and the contractions to both of these agents were more prolonged in the uremic vessels. CONCLUSIONS: The pattern of normal vasodilation to SNP but reduced vasodilation to acetylcholine is consistent with endothelial dysfunction due to impaired nitric oxide (NO) production in uremic vessels. Similar results have been demonstrated in vivo in uremia, one suggested mechanism being accumulation of endogenous inhibitors of NO synthase such as asymmetric dimethylarginine (ADMA). This in vitro study suggests that a short-lived circulating factor is not entirely responsible and that there may be an inherent abnormality in endothelial function in uremia, although the exact pathophysiology remains unclear. Endothelial dysfunction may predispose the patient to accelerated atherosclerosis and may be involved in the pathogenesis of hypertension in end-stage renal failure.

Acetylcholine↗

PubMed2005

Hyperhomocystinemia impairs endothelial function and eNOS activity via PKC activation.

OBJECTIVE: A risk factor for cardiovascular disease, hyperhomocystinemia (HHcy), is associated with endothelial dysfunction. In this study, we examined the mechanistic role of HHcy in endothelial dysfunction. METHODS AND RESULTS: Through the use of 2 functional models, aortic rings and intravital video microscopy of the cremaster, we found that arterial relaxation in response to the endothelium-dependent vessel relaxant, acetylcholine or the nitric oxide synthase (NOS) activator (A23187), was significantly impaired in cystathionine beta-synthase null (CBS(-/-)) mice. However, the vascular smooth muscle cell (VSMC) response to the nitric oxide (NO) donor (SNAP) was preserved in CBS(-/-) mice. In addition, superoxide dismutase and catalase failed to restore endothelium-dependent vasodilatation. Endothelial nitric oxide synthase (eNOS) activity was significantly reduced in mouse aortic endothelial cells (MAECs) of CBS(-/-) mice, as well as in Hcy-treated mouse and human aortic endothelial cells (HAECs). Hcy-mediated eNOS inhibition--which was not rescued by adenoviral transduction of superoxide dismutase and glutathione peroxidase, or by tetrahydrobiopterin, sepiapterin, and arginine supplementations in MAEC--was associated with decreased protein expression and increased threonine 495 phosphorylation of eNOS in HAECs. Ultimately, a protein kinase C (PKC) inhibitor, GF109203X (GFX), reversed Hcy-mediated eNOS inactivation and threonine 495 phosphorylation in HAECs. CONCLUSIONS: These data suggest that HHcy impairs endothelial function and eNOS activity, primarily through PKC activation.

Animals↗

PubMed2004

Endothelial function and carotid intima-media thickness in young healthy subjects among endothelial nitric oxide synthase Glu298-->Asp and T-786-->C polymorphisms.

BACKGROUND AND PURPOSE: To assess the role of the endothelial nitric oxide synthase (eNOS) gene variants as risk factors for early atherosclerosis, we sought to investigate whether two polymorphisms located in the exon 7 (Glu298-->Asp) and in the promoter region (T-786-->C) of the eNOS gene were associated with functional changes in the endothelium and carotid intima-media thickness (IMT). METHODS: Endothelium-dependent flow-mediated brachial artery dilation (FMD), endothelium-independent dilation response to glyceryl trinitrate (GTN), and carotid IMT were assessed by high-resolution ultrasound in 118 healthy young nonsmoker subjects (30.1+/-0.5 years) genotyped for the eNOS Glu298-->Asp and T-786-->C polymorphisms. RESULTS: Carotid IMT was inversely related to FMD by univariate analysis (r=-0.28, P=0.002) and after adjustment for possible confounders in all the subjects (P<0.01). Asp homozygotes had a significantly lower FMD than Glu carriers (Glu/Glu: 15.0%+/-1.0%, Glu/Asp: 13.3%+/-0.7%, Asp/Asp: 9.6%+/-1.6%; P=0.005), whereas FMD was unaffected by the T-786-->C variant. Neither the Glu298-->Asp nor the T-786-->C polymorphisms influenced the GTN-mediated dilation. With respect to Glu carriers, Asp/Asp genotype displayed a significantly greater carotid IMT (Glu/Glu: 0.37+/-0.01 mm, Glu/Asp: 0.35+/-0.01 mm, Asp/Asp: 0.45+/-0.03 mm; P=0.0002) and significant correlations between carotid IMT and FMD (r=-0.48, P=0.04) and between carotid IMT and resting brachial artery diameter (r=0.70, P=0.001). No difference in IMT was found across the T-786-->C genotypes. By multivariate regression analysis, Asp/Asp genotype was the only significant and independent predictor of flow-mediated brachial artery dilation (FMD) (P=0.04) and carotid intima-media thickness (IMT) (P=0.006). CONCLUSIONS: The eNOS Glu298-->Asp polymorphism may be related to early atherogenesis.

Adult↗

PubMed2006

The relationship between endothelial function in the brachial artery and intima plus media thickening of the coronary arteries in patients with chest pain syndrome.

Endothelial dysfunction precedes the development of clinical atherosclerosis. A decrease in endothelium-derived nitric oxide activity shows impaired vasodilator function and causes arterial intimal hyperplasia or thickening. Others and we have reported the close relation of endothelial function in brachial artery and coronary artery. To compare the flow-mediated endothelium-dependent vasodilation (FMD) in brachial artery and the intima+media area in coronary artery, we measured brachial artery vasodilator response following transient occlusion with high resolution ultrasound transducer and intima+media area in coronary arteries with intravascular ultrasound in 25 patients with normal coronary angiograms (age 61.6+/-8.7 years old, men 14 and women 11). FMD was measured at least 7 days after the cessation of all vasodilators. The mean FMD of 25 patients was 3.83+/-2.38%, the mean intima+media area in coronary arteries of 25 patients was 39.9+/-15.5% of total vessel wall. FMD has a close negative relation with the largest percent intima+media area (r=-0.77, p<0.01). Especially, the patients whose FMD was less than 3.83% had larger percent intima+media area than those whose FMD was 3.83% or more (48.7+/-10.7% versus 30.3+/-14.2%, p<0.01). There is an intima+media thickening even in the patients who had normal coronary angiograms, and that the percent intima+media area correlated with FMD. The measurement of FMD is useful for screening the coronary artery intima+media thickening noninvasively. The pathogenesis of acute coronary syndrome has been reported to be the plaque rupture even in the patients with normal coronary angiograms. Thus, we must pay much attention in the patients with impaired FMD even in the normal coronary angiograms.

Aged↗

PubMed2003

Functional endothelial cells derived from rhesus monkey embryonic stem cells.

We have used rhesus monkey embryonic stem (ES) cells to study endothelial cell development. Rhesus ES cells (R366.4 cell line) exposed to medium containing vascular endothelial growth factor (VEGF), basic fibroblast growth factor (bFGF), insulin-like growth factor (IGF), and epidermal growth factor (EGF) assumed a relatively uniform endothelial cell morphology and could be propagated and expanded with a consistent phenotype and normal karyotype. When placed in Matrigel, these rhesus ES cell-derived endothelial cells (RESDECs) formed capillary-like structures characteristic of endothelial cells. Immunohistochemical and flow cytometric analysis of RESDECs showed that they take up acetylated low-density lipoprotein (LDL), express CD146, von Willebrand factor, and the integrin alpha v beta 3, and bind the lectin ulex europaeus agglutinin-1. These cells also express the VEGF receptor Flk-1 and secrete VEGF. When introduced in a Matrigel plug implanted subcutaneously in mice, RESDECs formed intact vessels and recruited new endothelial cell growth. In vivo function was demonstrated by coinjection of RESDECs with murine tumor cells subcutaneously into immunocompromised adult mice. RESDECs injected alone did not form measurable tumors. Tumor cells grew more rapidly and had increased vascularization when coinjected with the RESDECs. Immunohistochemical staining demonstrated that the RESDECs participated in forming the tumor neovasculature. RESDECs provide a novel means to examine the mechanisms of endothelial cell development, and may open up new therapeutic strategies.

Animals↗

PubMed2002

Cardiac surgery: myocardial energy balance, antioxidant status and endothelial function after ischemia-reperfusion.

Myocardial and endothelial damage is still a widely debated problem during the ischemia-reperfusion sequence in heart surgery. We evaluated myocardial purine metabolites, antioxidant defense mechanisms, oxidative status and endothelial dysfunction markers in 14 patients undergoing coronary artery by-pass graft (CABG). Heart biopsies were taken before aortic cross-clamping (t1), before clamp removal (t2) and 30 min after reperfusion (t3); perchloric extracts of the tissue were analyzed for glutathione, NAD, nucleotide nucleoside and base content by capillary electrophoresis (CE). In plasma samples from the coronary sinus we evaluated: nitrate and nitrite concentrations by CE, plasma glutathione peroxidase (plGPx) by ELISA, endothelin-1 (ET-1) by RIA and reactive oxygen metabolites (ROM) by colorimetric assay. During the ischemic period (t2) we observed a reduction in cellular NAD and GSH levels, as well as nitrate, nitrite and plGPx. ATP and GTP levels decreased and their catabolic products AMP, GMP, IMP, adenosine, inosine and hypoxanthine accumulated. The energy charge, ATP/ADP ratio, and nucleotide/(nucleoside + base) ratios decreased. At t3, levels of plasma ET-1 increased and monophosphate nucleotides tended to return to basal values. The energy charge did not increase but the nucleotide/(nucleoside + nucleobase) ratio recovered to some extent. Levels of nitrates plus nitrites continued to decrease. No significant variation in ROM levels was observed. Our data indicate that oxidative stress and endothelial damage are major events during CABG, overwhelming the scavenging capacity of the myocyte and preventing restoration of the normal energy balance for 30 min after reperfusion. The AMP deaminase pathway leading to IMP production is active during ischemia and adenosine is not the main compound derived from ATP break-down in the human heart. The possible role of extracorporeal circulation is also discussed.

Aged↗

PubMed2003

Tetrahydrobiopterin-dependent preservation of nitric oxide-mediated endothelial function in diabetes by targeted transgenic GTP-cyclohydrolase I overexpression.

Increased production of reactive oxygen species and loss of endothelial NO bioactivity are key features of vascular disease states such as diabetes mellitus. Tetrahydrobiopterin (BH4) is a required cofactor for eNOS activity; pharmacologic studies suggest that BH4 may mediate some of the adverse effects of diabetes on eNOS function. We have now investigated the importance and mechanisms of BH4 availability in vivo using a novel transgenic mouse model with endothelial-targeted overexpression of the rate-limiting enzyme in BH4 synthesis, guanosine triphosphate-cyclohydrolase I (GTPCH). Transgenic (GCH-Tg) mice demonstrated selective augmentation of endothelial BH4 levels. In WT mice, induction of diabetes with streptozotocin (STZ) increased vascular oxidative stress, resulting in oxidative loss of BH4, forming BH2 and biopterin. Endothelial cell superoxide production in diabetes was increased, and NO-mediated endothelium-dependent vasodilatation was impaired. In diabetic GCH-Tg mice, superoxide production from the endothelium was markedly reduced compared with that of WT mice, endothelial BH4 levels were maintained despite some oxidative loss of BH4, and NO-mediated vasodilatation was preserved. These findings indicate that BH4 is an important mediator of eNOS regulation in diabetes and is a rational therapeutic target to restore NO-mediated endothelial function in diabetes and other vascular disease states.

Animals↗

PubMed2003

Insulin resistant young subjects at risk of accelerated atherosclerosis exhibit a marked reduction in peripheral endothelial function early in life but not differences in intima-media thickness.

Reduced bio-availability of nitric oxide leading to disturbed flow mediated (endothelial dependent) vasodilation (FMD) has been shown to be an early functional abnormality of the vascular system in insulin resistant individuals and other subjects at high risk for accelerated atherosclerosis. In addition, an increase of the intima-media thickness (IMT) is regarded as an early marker of morphological alterations of the vessel wall. Whether endothelial dysfunction (ED) is evident already at an early stage when morphological changes of the vessel wall are not apparent is still an open question. We, therefore, examined IMT and peripheral endothelial function in a group of young insulin resistant subjects in a cross-sectional study and compared these results with a metabolically healthy (insulin sensitive) control group. We measured IMT (distal common carotid arteries), endothelium-dependent and endothelium-independent vasodilation (flow mediated and glyceroltrinitrate induced vasodilation of the brachial artery) non-invasively with high resolution ultrasound (13 MHz) in 91 young normoglycemic subjects (40/51 M/F, median: 31 years, range 18-50 years). Insulin sensitivity was measured with a euglycemic, hyperinsulinemic glucose clamp. Despite a marked reduction in flow-mediated vasodilation in insulin resistant (IR) subjects (FMD: median 3.4%, range -4.0 to 12.5 in IR versus 6.6%, range -1.2 to 20.1% in insulin sensitive subjects; P = 0.017), there was no difference in endothelial independent vasodilation (16.3%, range 5.7-41.0% versus 16.1%, range 0.5-39.2%) and in IMT (0.50 mm, range 0.39-0.66 and 0.51, 0.40-0.70 mm, respectively). These data suggest that ED can be detected very early in the life of insulin resistant subjects whereas no significant structural changes, indicated by a thickening of the intima-media layer, could be found. We therefore conclude that for identification of subjects with a high risk for accelerated atherosclerosis at an early stage, measurement of flow mediated vasodilation of the brachial artery may be more helpful than measuring thickness of the vascular wall.

Adolescent↗

PubMed2006

Effects of low birth weight in 8- to 13-year-old children: implications in endothelial function and uric acid levels.

Low birth weight has been associated with an increased incidence of adult cardiovascular disease. Endothelial dysfunction and high levels of serum uric acid are associated with hypertension. In this study, we have determined whether uric acid is related to blood pressure and vascular function in children with low birth weight. We evaluated vascular function using high-resolution ultrasound, blood pressure, and uric acid levels in 78 children (35 girls, 43 boys, aged 8 to 13 years). Increasing levels of uric acid and systolic blood pressure were observed in children with low birth weight. Birth weight was inversely associated with both systolic blood pressure and uric acid; on the other hand, uric acid levels were directly correlated with systolic blood pressure in children of the entire cohort. Low birth weight was associated with reduced flow-mediated dilation (r=0.427, P<0.001). Because the children with low birth weight had elevated uric acid as well as higher systolic blood pressure levels, we evaluated the correlation between these variables. In the low birth weight group, multiple regression analysis revealed that uric acid (beta=-2.886; SE=1.393; P=0.040) had a graded inverse relationship with flow-mediated dilation, which was not affected in a model adjusting for race and gender. We conclude that children with a history of low birth weight show impaired endothelial function and increased blood pressure and uric acid levels. These findings may be early expressions of vascular compromise, contributing to susceptibility to disease in adult life.

Adolescent↗