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PubMed2006

Effect of angiotensin II type 1 receptor antagonism on endothelial function: role of bradykinin and nitric oxide.

BACKGROUND: The important role of the endothelium for regulation of vascular tone, growth, inflammatory response, coagulation and thrombocyte adhesion has now been recognized. Endothelial function has largely been assessed as endothelium-dependent vasodilation, assuming that endothelium-dependent vasomotion represents a surrogate marker for other important endothelial functions. An important rational for this approach has been the observation that both endothelium-dependent vasomotion and other protective endothelial functions are at least partially mediated by nitric oxide. Accumulating clinical studies have now demonstrated a close and independent association of impaired endothelium-dependent vasodilation with cardiovascular events and prognosis. These findings have stimulated interest in treatment options to improve endothelial function in patients at high cardiovascular risk. DISCUSSION: This article describes recent insights into endothelial effects of both angiotensin-converting enzyme (ACE) inhibition and angiotensin II type 1 (AT1) receptor blockade, which have both been shown to improve endothelial function (i.e. by increasing endothelial nitric oxide availability via bradykinin-dependent endothelial nitric oxide release). ACE has a high affinity for bradykinin and degrades the peptide, so ACE inhibition may increase bradykinin-dependent effects by preventing bradykinin degradation. Interestingly, AT1-receptor blockade appears to stimulate the bradykinin-nitric oxide pathway by increased angiotensin II type 2 receptor activation. Moreover, both treatment strategies prevent increased inactivation of endothelial nitric oxide by oxygen radicals, by reducing AT1-receptor-dependent activation of the oxidant enzyme NADPH oxidase and increasing the activity of the vascular antioxidant enzyme extracellular superoxide dismutase. These beneficial effects of ACE inhibition and AT1-receptor blockade are likely to contribute to their effects on cardiovascular events.

Angiotensin II Type 1 Receptor Blockers↗

PubMed1998

Evaluation in vivo of the endothelial function of the native gastroepiploic artery.

The endothelial function of a coronary bypass graft is an important aspect, contributing not only to its patency but to its functional performance. To evaluate this aspect in vivo, we studied 16 patients who underwent selective catheterization of the native gastroepiploic artery (GEA). Quantitative angiography of the GEA was performed at baseline, after 2 minutes' infusion of acetylcholine in three ascending doses, and after 2 mg isosorbide dinitrate injection directly into the GEA. Mean GEA diameter was 2.02 +/- 0.38 mm at baseline. We observed dose-dependent vasodilation during acetylcholine infusion: The mean diameter increased slightly to 2.11 +/- 0.32 mm (+6%, not significant) with the second dosage and, more significantly, with the highest dosage, to 2.32 +/- 0.33 mm (+18%, p < 0.001). More important vasodilation was observed after administration of nitrates (+36%, p < 0.001). We found no difference between patients with and without coronary artery disease and no relationship with risk factors for atherosclerosis. A positive correlation was seen between the vasodilation observed after nitrate administration and the highest dose of acetylcholine (r = 0.728, p = 0.002). In conclusion, the GEA demonstrates a notable vasodilatory response to nitrates (non-endothelium-dependent) and a dose-related dilator response to acetylcholine, reflecting preserved endothelial function. This sensitivity should affect favorably the hemodynamic performance of grafts performed with GEA, as well as these grafts' long-term patency rate.

Acetylcholine↗

PubMed2000

Suppression of inflammation in primary systemic vasculitis restores vascular endothelial function: lessons for atherosclerotic disease?

BACKGROUND: Chronic inflammatory rheumatic disorders are associated with excess cardiovascular mortality. This may result from arteriosclerosis following inflammatory damage to the vessel wall by vasculitis. Our hypothesis that vasculitis results in arteriosclerosis by causing vascular endothelial dysfunction was tested in patients with primary systemic necrotizing vasculitis (SNV). METHODS AND RESULTS: Endothelial function was assessed in cross-sectional and longitudinal studies of patients with primary SNV by measuring flow-mediated, endothelium-dependent brachial artery vasodilatation. These patients exhibited marked endothelial dysfunction compared with controls. Remission induction in patients with active primary SNV restored endothelial function. CONCLUSIONS: Endothelial function is significantly impaired in adults with primary SNV, supporting the hypothesis that premature arteriosclerosis in chronic inflammatory rheumatic disorders results from endothelial dysfunction secondary to vasculitis. Normalization of endothelial function after the treatment of primary SNV suggests that early suppression of disease activity in chronic inflammatory rheumatic disorders may reduce long-term vascular damage. The role of inflammation in atheroma formation is increasingly appreciated; this work raises questions regarding the potential for anti-inflammatory therapy in atherosclerosis itself.

Brachial Artery↗

PubMed2004

Rationale and design of the Glitazones and the Endothelium (GATE) study: evaluation of rosiglitazone on endothelial function in patients with diabetes.

The vascular endothelium has emerged as a critical determinant of cardiovascular health and disease, and improving endothelial function is an important target for therapy. Accumulating evidence suggests that insulin resistance in patients with diabetes and the metabolic syndrome may impair endothelial function, uncovering a proinflammatory, proatherosclerotic vascular phenotype. The rationale and design of the Glitazones and the Endothelium (GATE) study is presented. The GATE study is a randomized, double-blind study for the evaluation of the effects of rosiglitazone versus placebo on endothelial function when used as an add-on therapy in patients with diabetes currently treated with oral therapy. It is hypothesized that the peroxisome proliferator-activated receptor-gamma agonist rosiglitazone will improve endothelium-dependent vasodilation, and that this effect will be related to improvements in insulin sensitivity, with concomitant reductions in whole-body insulin resistance. Furthermore, the beneficial effects of rosiglitazone will be additive to those of existing oral therapies that may modulate endothelial function. Because endothelial dysfunction plays a pivotal role in the development and progression of atherosclerosis, the GATE study may provide the rationale and impetus for the aggressive treatment of insulin-resistant patients with glitazone therapy.

Administration, Oral↗

PubMed2003

Residual C-peptide secretion and endothelial function in patients with Type II diabetes.

Recent studies have demonstrated that C-peptide exerts beneficial effects on endothelial function. To investigate the relationship between residual pancreatic C-peptide secretion and endothelial function in patients with well controlled or poorly controlled Type II diabetes, we studied 100 patients with Type II diabetes that were free from diabetic neuropathy. In all patients, insulin resistance, residual pancreatic C-peptide secretion, endothelial function and oxidative stress were investigated using the homoeostasis model assessment (HOMA) index, glucagon bolus test, brachial reactivity, Trolox equivalent antioxidant capacity (TEAC) and thiobarbituric acid-reacting substances (TBARS). The patients were categorized into quartiles on the basis of plasma HbA(1c) (glycated haemoglobin) concentration. Analysis of the data showed significant increases in plasma glucose concentration, HOMA index, microalbuminuria and TBARS, and significant decreases in plasma C-peptide, AUC (area under the curve) plasma C-peptide and TEAC, through the different quartiles (from the lowest to the highest HbA(1c) concentration). With regard to parameters of endothelial function, changes in diameter showed a significant declining trend through the different quartiles. Endothelial-dependent changes in diameter were independently and significantly associated with AUC C-peptide levels, TEAC and TBARS. In conclusion, our study demonstrated that patients with Type II diabetes with good residual C-peptide secretion are better protected from endothelial dysfunction that those with poor C-peptide secretion.

Aged↗

PubMed2004

Impact of left ventricular ejection fraction on endothelial function in patients with coronary artery disease.

BACKGROUND: Endothelial dysfunction is present in patients with coronary artery disease (CAD) or with congestive heart failure. HYPOTHESIS: This study was performed to evaluate the impact of systolic heart function on endothelial function in patients with CAD. METHODS: The study population consisted of 283 consecutive patients (mean age 59 years, 176 men) undergoing coronary angiography. Endothelial function was assessed by measuring flow-mediated vasodilation (FMD) of the brachial artery. RESULTS: Patients (n = 236) with an ejection fraction (EF) > or = 55% on routine echocardiogram were younger (mean age 58 vs. 62 years), showed a lower prevalence of diabetes (15 vs. 38%) and myocardial infarction (13 vs. 66%), and showed a higher FMD (4.8 +/- 2.4 vs. 4.0 +/- 2.0%, p < 0.05) than patients (n = 47) with an EF < 55%. The correlation coefficient between FMD/endothelial function and EF/systolic heart function was 0.149 (p < 0.02) in the overall study population. Multivariate analysis showed that of age, gender, frequency of diabetes mellitus, myocardial infarction, and CAD extent, EF was the only significant independent parameter correlating with FMD in patients with CAD. CONCLUSIONS: Compared with the other tested risk factors, EF surprisingly was the only significant independent parameter correlating with endothelial function in patients with CAD. Our results support the view that endothelial function is an independent prognostic factor in patients with CAD.

Brachial Artery↗

PubMed2001

Improved endothelial function with metformin in type 2 diabetes mellitus.

OBJECTIVES: This study was designed to assess the effect of metformin on impaired endothelial function in type 2 diabetes mellitus. BACKGROUND: Abnormalities in vascular endothelial function are well recognized among patients with type 2 (insulin-resistant) diabetes mellitus. Insulin resistance itself may be central to the pathogenesis of endothelial dysfunction. The effects of metformin, an antidiabetic agent that improves insulin sensitivity, on endothelial function have not been reported. METHODS: Subjects with diet-treated type 2 diabetes but without the confounding collection of cardiovascular risk factors seen in the metabolic syndrome were treated with metformin 500 mg twice daily (n = 29) or placebo (n = 15) for 12 weeks. Before and after treatment, blood flow responses to intraarterial administration of endothelium-dependent (acetylcholine), endothelium-independent (sodium nitroprusside) and nitrate-independent (verapamil) vasodilators were measured using forearm plethysmography. Whole-body insulin resistance was assessed on both occasions using the homeostasis model (HOMA-IR). RESULTS: Subjects who received metformin demonstrated statistically significant improvement in acetylcholine-stimulated flows compared with those treated with placebo (p = 0.0027 by 2-way analysis of variance), whereas no significant effect was seen on nitroprusside-stimulated (p = 0.27) or verapamil-stimulated (p = 0.40) flows. There was a significant improvement in insulin resistance with metformin (32.5% reduction in HOMA-IR, p = 0.01), and by stepwise multivariate analysis insulin resistance was the sole predictor of endothelium-dependent blood flow following treatment (r = -0.659, p = 0.0012). CONCLUSIONS: Metformin treatment improved both insulin resistance and endothelial function, with a strong statistical link between these variables. This supports the concept of the central role of insulin resistance in the pathogenesis of endothelial dysfunction in type 2 diabetes mellitus. This has important implications for the investigation and treatment of vascular disease in patients with type 2 diabetes mellitus.

Blood Flow Velocity↗

PubMedDate not supplied

Clinical assessment of endothelial function.

The endothelium is crucial in the maintenance of normal vascular function and disturbance of this balance is a key early event in the development of vascular disease. A wide range of techniques currently exists for assessment of endothelial function in both the coronary and the peripheral vasculature. Many of these in vivo tests have concentrated on measuring nitric oxide bioavailability, however more recently methods for measuring other vascular parameters, such as tissue-plasminogen activator release, have been used. Furthermore indirect systemic measurements of endothelial function and endothelial progenitor cells have been investigated. These methods have given great insights into the pathophysiology of atherosclerosis and have aided in the development of a number of antiatherosclerotic therapies. Importantly the methods used to date for assessing endothelial function in vivo are accurate, reproducible and correlate with the future risk of cardiovascular events. The development of new techniques and the constant refinement of established techniques suggest that many more insights are to be gained from clinical assessment of endothelial function.

Brachial Artery↗

PubMed2001

A new noninvasive method for evaluation of coronary endothelial function in hypertensive patients based on change in diameter of the left main coronary artery induced by cold pressor test using echocardiography.

BACKGROUND: Coronary endothelial function is frequently studied by measuring the vasodilator response of coronary arteries to acetylcholine or to cold pressor test by invasive quantitative coronary angiography. Because invasive methods have substantial inherent limitations, studies should attempt to evaluate coronary endothelial function noninvasively. HYPOTHESIS: We attempted to evaluate the accuracy of measurement of the percent change in diameter of the left main trunk induced by cold pressor test with two-dimensional (2-D) echocardiography. Furthermore, we applied this method to the evaluation of coronary artery endothelial function in hypertensive patients. METHODS: We measured the left main trunk diameter in 21 subjects (51 +/- 4 years) before and after cold pressor test using quantitative coronary angiography followed immediately by 2-D echocardiography. The accuracy of measurement of the left main trunk diameter and its percent change by echocardiography was evaluated by comparing the values obtained by the two methods. In addition, using echocardiography, we compared left main trunk diameter responses to cold pressor test in 16 hypertensive patients [51 +/- 5 years (mean +/- standard deviation)] and 16 matched healthy subjects (50 +/- 4 years). RESULTS: Although there was only a weak correlation between the absolute values of the left main trunk diameter measured by the two methods (r = 0.61; p = 0.04), a strong correlation was found between the percent change in diameter measured by the two methods (r = 0.93; p = 0.0001). The percent change in diameter of the left main trunk induced by cold pressor test in hypertensive patients (-3.7 +/- 10.6%) was significantly lower than that in control subjects (13.2 +/- 6.8%, p = 0.0001). CONCLUSIONS: Percent change in diameter of the left main trunk induced by cold pressor test can be evaluated accurately using 2-D echocardiography. Our study showed reduced vasodilation or vasoconstriction of the left main trunk after cold pressor test in hypertensive patients compared with healthy subjects, indicating impaired coronary endothelial function in hypertensive patients. The present echocardiographic method is a potentially useful new noninvasive method for evaluating coronary endothelial function.

Adult↗

PubMed2000

[Endothelial function in coronary segments previously treated with balloon angioplasty].

INTRODUCTION AND OBJECTIVES: Coronary angioplasty leads to endothelial disruption and a further rendotelization. The aim of our study was to determine the status of endothelial function in previously dilated coronary segments without restenosis. METHODS: Endothelium-dependent vasomotion was analysed in twelve patients with single vessel coronary disease six month after angioplasty by selective intracoronary doses of acetylcholine (10-6, 10-5, 10-4 M) in the previously treated artery. The control group was made up of seven patients with no evidence of significant coronary stenosis and without risk factors. Vasomotor response at the different doses of acetylcholine was determined by quantitative coronary angiography. RESULTS: Endothelial function showed a global vasodilator response in the dilated segment at the maximum dose of acetylcholine (increase in lumen diameter 3.6 +/- 3.5%), similar to the response observed in the control group (increase of luminal diameter 3 +/- 6%; p = NS). In particular, 8 patients (67%) showed a normal endotelial function, while 4 patients (33%) showed a vasoconstrictor response. A positive correlation was detected between the response to the maximun dose of acetylcholine and the percent of residual stenosis at 6 months of follow-up (r = 0.67; p = 0.02). CONCLUSIONS: In patients treated with coronary angioplasty without restenosis, the dilated segments frequently showed normal endothelial function. Greater residual stenosis at the dilated segment was associated with less impairment in endothelial function.

Angioplasty, Balloon↗

PubMed2003

Effect of alcohol on endothelial function in healthy subjects.

While studies have shown that red wine improves endothelial function, the effect of pure alcohol, the common denominator of all alcoholic beverages, on endothelial function has not been defined. The effect of oral intake of alcohol (one ounce--a dose corresponding to two drink equivalents) on flow-mediated dilatation of the brachial artery was studied in 12 healthy subjects using high-resolution ultrasonography according to a randomized, sham procedure-controlled, single-blind protocol. Alcohol produced a significant vasodilatation of the brachial artery at resting conditions. Furthermore, it led to a significant increase of the brachial artery diameter at reactive hyperemia; however, the percentage flow-mediated dilatation did not change. This study shows, for the first time, that acute moderate intake of alcohol has a potent dilating effect on large arteries both at resting and at reactive hyperemic conditions, without affecting flow-mediated dilatation as a percentage. This may be useful for explaining the divergent effect of different alcoholic beverages on endothelial function and provides valuable insight into the mechanisms involved in the vascular effects of alcohol.

Adult↗

PubMed2001

Simvastatin treatment is associated with improvement in coronary endothelial function and decreased cytokine activation in patients after heart transplantation.

OBJECTIVES: This study was designed to assess the association between 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase inhibition, coronary endothelial function and cytokine activation in heart transplant recipients without angiographically detectable disease. BACKGROUND: Coronary endothelial dysfunction contributes to cardiac allograft vasculopathy. The vasoprotective effects of statins in heart transplant recipients may include restoration of endothelial function and suppression of allograft inflammatory activity. METHODS: Heart transplant recipients (one to three years after heart transplant) were divided into three groups based on the total cholesterol levels: group 1 (n = 21), patients with a history of hypercholesterolemia adequately controlled with simvastatin; group 2 (n = 19), patients with hypercholesterolemia not adequately treated with simvastatin; and group 3 (n = 40), patients without hypercholesterolemia. Coronary vasomotor function and intimal thickness as well as coronary sinus and aortic cytokine concentrations (tumor necrosis factor [TNF]-alpha, interleukin [IL]-6 and soluble IL-2 receptor) were investigated. In a prospective one-year follow-up study, changes in coronary endothelial function and cytokine levels were compared between 11 hypercholesterolemic patients treated with simvastatin and 9 controls. RESULTS: Epicardial and microvascular endothelial functions were better in groups 1 and 3 than they were in group 2 (p < 0.01 and p < 0.05). Transcardiac IL-6 and TNF-alpha gradients were significantly increased in groups 2 and 3 compared with group 1 (IL-6: p < 0.05; TNF-alpha: p < 0.01). Plaque areas were significantly increased in groups 1 and 2 (p < 0.05 vs. group 3), whereas lumen area was increased in group 2 compared with group 1 (p < 0.05), demonstrating adaptive vascular remodeling. In patients treated with simvastatin, coronary endothelial function and cardiac cytokine activity significantly improved during the one-year follow-up. CONCLUSIONS: Inhibition of allograft inflammatory activity and attenuation of the coronary endothelial dysfunction observed in cardiac transplant recipients during treatment with simvastatin may represent an important mechanism by which HMG-CoA reductase inhibitors protect against the development of cardiac allograft vasculopathy.

Coronary Angiography↗

PubMed1999

Endothelial function in proteinuric renal disease.

Nephrotic-range proteinuria is associated with a several-fold increase risk of cardiovascular infarction. This increased risk is accompanied by endothelial dysfunction, which is not related to increased blood pressure and is not correctable by acute administration of L-arginine. The latter is in direct contrast to what has been found in patients with primary hypercholesterolemia, suggesting that either hypoalbuminemia itself or other aspects of the dyslipidemia characteristic of the nephrotic syndrome impair endothelial function. Lysophosphatidylcholine (lyso-PC) is formed during oxidative modification of cholesterol, and lyso-PC in oxidized low-density lipoprotein (LDL) is responsible for reduced endothelial function in vitro. However, in the circulation, lyso-PC is tightly bound to albumin. Indeed, the addition of albumin can restore endothelial function, which was previously disturbed by lyso-PC. Hypoalbuminemia induces a shift in lyso-PC to lipoproteins, notably LDL, and to erythrocytes. The latter directly induces a reduction in deformability that can also be corrected by the addition of albumin. Hypoalbuminemia may disturb endothelial function, either by directly affecting Gi-protein-dependent signal transduction or indirectly by changing the configuration of the cell membrane. Such a change in cell membrane configuration will disturb binding of ligands to receptors and of endothelial nitric oxide (NO) synthase to caveolin. However, other pathways have been suggested, such as stimulation by lyso-PC of vasoconstriction mediated by protein kinase C. It remains to be shown whether lipid-lowering and antiproteinuric strategies have independent positive effects on endothelial function in nephrotic subjects.

Animals↗

PubMed2006

Steroid pulse therapy impaired endothelial function while increasing plasma high molecule adiponectin concentration in patients with IgA nephropathy.

BACKGROUND: Decreased plasma adiponectin is associated with impaired endothelial function and, thereby, increased risk for cardiovascular events. Glucocorticoid (GC) affects vascular endothelial cells either favourably or harmfully depending upon the dosages and duration. We examined the effect of GC pulse therapy on vascular endothelial function. METHODS: Fourteen young patients with IgA nephropathy were evaluated for flow-mediated vasodilation (FMD), plasma levels of adiponectin both in high molecular weight (HMW adiponectin) form and in single molecular form (total adiponectin), hepatocyte growth factor (HGF), asymmetric dimethylarginine (ADMA), and high-sensitive C-reactive protein, before and after a course of GC pulse therapy. RESULTS: GC pulse therapy significantly decreased FMD (from 7.2 +/- 2.6 to 5.7 +/- 2.5%, P < 0.01). Meanwhile, plasma adiponectin levels were significantly augmented (total adiponectin: from 10.2 +/- 4.0 to 12.1 +/- 6.3 microg/ml, P < 0.05; HMW: from 6.5 +/- 3.2 to 7.7 +/- 3.3 microg/ml, P < 0.05). In parallel, elevated concentrations of serum HGF (from 0.28 +/- 0.12 to 0.63 +/- 0.38 ng/ml, P < 0.01) and plasma ADMA (from 0.45 +/- 0.07 to 0.53 +/- 0.04 nmol/ml, P < 0.05) were observed. CONCLUSIONS: GC pulse therapy impaired endothelial function while increasing plasma adiponectin levels, which may in turn restore the endothelial function in patients with IgA nephropathy.

Adiponectin↗

PubMed2005

Simvastatin versus ezetimibe: pleiotropic and lipid-lowering effects on endothelial function in humans.

BACKGROUND: Statins may exert important pleiotropic effects, ie, improve endothelial function, independently of their impact on LDL cholesterol. In humans, however, pleiotropic effects of statins have never been unequivocally demonstrated because prolonged statin treatment always results in reduced LDL cholesterol levels. We therefore tested the hypothesis that similar reductions in LDL cholesterol with simvastatin and ezetimibe, a novel cholesterol absorption inhibitor, result in different effects on endothelial function. METHODS AND RESULTS: Twenty patients with chronic heart failure were randomized to 4 weeks of simvastatin (10 mg/d) or ezetimibe (10 mg/d) treatment. Flow-dependent dilation (FDD) of the radial artery was determined by high-resolution ultrasound before and after intra-arterial vitamin C to determine the portion of FDD inhibited by radicals (DeltaFDD-VC). Activity of extracellular superoxide dismutase, a major vascular antioxidant enzyme system, was determined after release from the endothelium by a heparin bolus injection. Endothelial progenitor cells were analyzed with an in vitro assay. Simvastatin and ezetimibe treatment reduced LDL cholesterol to a similar extent (15.6% versus 15.4%; P=NS), whereas changes in mevalonate, the product of HMG-CoA-reductase, differed between groups (Deltamevalonate-simvastatin, -1.04+/-0.62 versus Deltamevalonate-ezetimibe, 1.79+/-0.94 ng/mL; P<0.05 between groups). Importantly, FDD was markedly improved after simvastatin (10.5+/-0.6% versus 5.1+/-0.7%; P<0.01) but not after ezetimibe treatment (5.6+/-0.5% versus 5.8+/-0.6%; P=NS). DeltaFDD-VC was substantially reduced after simvastatin but not after ezetimibe treatment. Extracellular superoxide dismutase activity was increased by >100% (P<0.05) after simvastatin but not ezetimibe treatment. Simvastatin treatment increased the number of functionally active endothelial progenitor cells, whereas ezetimibe had no effect. CONCLUSIONS: Four weeks of simvastatin treatment improves endothelial function independently of LDL cholesterol lowering, at least in part by reducing oxidant stress. Simvastatin may thereby exert important pleiotropic effects in humans.

Anticholesteremic Agents↗

PubMed1996

Burn injury alters coronary endothelial function.

This study examined the effects of burn injury on coronary endothelial function and coronary vascular reactivity. Adult rabbits were given a scald burn over 30% of the total body surface area (or sham burn for controls) and resuscitated with Ringer's lactate solution (4 ml/kg/% burn). Subgroups of burned (n = 6) and sham-burned (n = 6) animals were sacrificed at 2, 6, and 24 hr after injury; hearts were harvested and perfused. Changes in coronary perfusion pressure (CPP, mmHg) and coronary vascular resistance (CVR, mmHg/min) were determined at a constant preload and constant coronary flow rate. Changes in coronary endothelial function were determined by the ability of the endothelium to release cGMP as an indicator of nitric oxide production. Compared to values measured in sham burns, CPP and CVR progressively fell during the early postburn period but increased toward values measured in the sham burn group by 24 hr. Cyclic GMP, fmole/ml of coronary perfusate, was significantly lower in burned hearts (27 +/- 1) compared to values measured in effluents from sham burn hearts (310 +/- 40, P < 0.05). Alterations in coronary effluent cGMP levels after burn injury suggest that thermal injury disrupts coronary endothelial function, likely contributing to postburn changes in cardiac performance.

Acetylcholine↗

PubMed2002

Interaction of 5-methyltetrahydrofolate and tetrahydrobiopterin on endothelial function.

The present study was designed to investigate the interaction between 5-methyltetrahydrofolate and tetrahydrobiopterin in modulating endothelial function. Tetrahydrobiopterin is a critical cofactor for nitric oxide synthase and maintains this enzyme as a nitric oxide- versus superoxide-producing enzyme. The structure of 5-methyltetrahydrofolate is similar to tetrahydrobiopterin and both agents have been shown to improve endothelium-dependent vasodilatation. We hypothesized that 5-methyltetrahydrofolate interacts with nitric oxide synthase in a fashion analogous, yet independent, of tetrahydrobiopterin to improve endothelial function. We demonstrate that 5-methyltetrahydrofolate binds the active site of nitric oxide synthase and mimics the orientation of tetrahydrobiopterin. Furthermore, 5-methyltetrahydrofolate attenuates superoxide production (induced by inhibition of tetrahydrobiopterin synthesis) and improves endothelial function in aortae isolated from tetrahydrobiopterin-deficient rats. We suggest that 5-methyltetrahydrofolate directly interacts with nitric oxide synthase to promote nitric oxide (vs. superoxide) production and improve endothelial function. 5-Methyltetrahydrofolate may represent an important strategy for intervention aimed at improving tetrahydrobiopterin bioavailability.

Acetylcholine↗

PubMed2006

[Carotid intimal-medial thickening and endothelial function in coronary artery disease].

OBJECTIVE: To investigate the correlation between the endothelial function and the carotid intimal-medial thickening (IMT) in a population of patients with coronary artery disease, as well as that between the endothelial function and carotid IMT with the severity of the coronary lesions. METHODS: Forty-three patients aged 60.5+/-9.2 years, (67.4% males) with coronary artery disease at the coronariography were studied. Endothelial function was assessed using the brachial artery reactivity test (BART), which measured the percentage of flow-mediated dilatation (%FMD). The carotid IMT was evaluated through vascular ultrasound. RESULTS: The mean %FDM was 4.7 +/- 3.6 and the mean carotid IMT was 1.08 +/- 0.23 mm. The carotid MIT and %FMD measurements showed a statistically significant correlation, with Spearmans coefficient of 0.315, p= 0.042, demonstrating that lower %FMD values corresponded to an increased carotid IMT (r = -0.315, p = 0.042). There was no correlation between %FMD or IMT and the severity of coronary lesions. CONCLUSIONS: The presence of a correlation between carotid IMT and %FMD demonstrates a concomitance of anatomical and functional vascular alterations in coronary artery disease, regardless of the severity of the atherosclerotic lesions.

Atherosclerosis↗