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Results for “Endothelial function”

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PubMed2002

[Changes of antioxidative capacity and endothelial function before and after treatment among patients with high altitude pulmonary edema].

OBJECTIVE: To investigate the changes of antioxidative capacity and endothelial function among patients with high altitude pulmonary edema (HAPE). METHODS: The serum levels of SOD, MDA, GSH, NO, NOS and ET-1 were measured before and after treatment among 34 cases of patients with HAPE, and 20 local healthy volunteers served as control. RESULTS: The serum levels of SOD, GSH, NO and NOS were lower in patient-group before treatment than after treatment and those in control-group significantly (P < 0.01), while the concentration of MDA and ET-1 were higher in patient-group before treatment than after treatment and those in the control-group significantly (P < 0.01). The serum levels of SOD, MDA, GSH, NO, NOS and ET-1 were not different between patient-group after treatment and the control-group (P > 0.05). CONCLUSION: The results indicated that changes of SOD, MDA, GSH, NO, NOS and ET-1 may participate in the course of HAPE.

Adolescent↗

PubMed1997

Corneal endothelial function after extracapsular cataract extraction and phacoemulsification.

PURPOSE: To compare the morphology and function of the corneal endothelium in the early postoperative period after extracapsular cataract extraction (ECCE) and phacoemulsification. SETTING: University Eye Clinic of Trieste, Italy. METHODS: In this prospective, randomized study of patients scheduled for cataract surgery, 40 patients were divided into two groups of 20 patients each. Group 1 had ECCE and Group 2, phacoemulsification; both had capsular bag intraocular lens (IOL) implantation. Preoperatively and 7 and 30 days postoperatively, a complete ophthalmological examination, endothelial specular microscopy, ultrasonic pachymetry, and anterior segment fluorophotometry were done. Visual acuity, endothelial cell density, cell size variation coefficient, corneal thickness, endothelial permeability coefficient, and endothelial pump function were studied. RESULTS: Visual acuity was better 7 days after phacoemulsification than after ECCE, but no differences were observed after 30 days. No significant differences in postoperative loss of endothelial cells were found between the two groups. Coefficient of variation in size, corneal thickness, and endothelial permeability significantly increased in both groups 7 days postoperatively, but only in the ECCE group 30 days postoperatively; the differences between the two groups were statistically significant. Endothelial pump function significantly increased after 7 days in only the phacoemulsification group. CONCLUSIONS: Functional endothelial failure occurred in the early period after ECCE. Phacoemulsification seemed to minimize postoperative functional damage to the endothelium.

Aged↗

PubMed2002

Frequent occurrence of anticardiolipin antibodies, Factor V Leiden mutation, and perturbed endothelial function in chronic myeloproliferative disorders.

Chronic myeloproliferative disorders (MPD) are characterized by a high incidence of thrombohaemorrhagic complications, possibly related to platelet abnormalities and disturbances of the coagulation system. In an attempt to define abnormalities in coagulation and fibrinolysis, we investigated risk markers for venous thromboembolism, fibrinolytic, and haemostatic system activation markers and antiphospholipid antibodies in blood samples from 50 MPD patients and 30 controls. Compared with controls median levels of protein S free and protein C were significantly decreased in the patients (0.27 vs. 0.38 arbitrary units; P < 0.001 and 0.86 vs. 0.99 arbitrary units; P < 0.001, respectively), and activated partial thromboplastin time was significantly prolonged in patients (33 vs. 27 sec; P < 0.001). No differences were observed in levels of antithrombin, thrombin-antithrombin complex, and fibrin D-dimer. In patients the median value of thrombomodulin was significantly increased indicating perturbed endothelial function. Anticardiolipin antibodies of IgM subtype (median 38 U/mL, 33-99) were detected in 11 patients (22%) and only in one control (3%) (P < 0.021; patients vs. controls). Seven patients were heterozygous for the Factor V Leiden, one patient was heterozygous for the prothrombin G20210A mutation, and one patient was homozygous for the Factor V Leiden mutation. Among controls, two were heterozygous for the Factor V Leiden mutation. Comparing the allele frequency of the Factor V Leiden mutation in patients with MPD and the background population disclosed a significantly increased allele prevalence of the Factor V Leiden mutation in the patients (9% vs. 3.4%; P = 0.003). Alterations in the level of anticoagulant proteins, disturbances of endothelial cell function, and the presence of cardiolipin antibodies and Factor V Leiden mutation may increase the cumulative thrombotic risk in MPD besides the risk imposed by platelet activation.

Adult↗

PubMed1999

Effect of lipid-lowering therapy on vasomotion and endothelial function.

The recent clinical trials of lipid lowering have established the benefit of this therapy in men and women with, or at high risk for, cardiovascular disease. It is now thought that most of the reduction in the risk of clinical events is due to functional rather than anatomic changes in atherosclerotic arteries. Cholesterol-lowering drugs improve endothelial vasomotor function and vascular nitric oxide in patients with coronary artery disease over several months. These changes in vasomotor function may reflect other beneficial changes that are regulated by nitric oxide such as the reduced recruitment and activation of inflammatory cells and a shift in the coagulation balance to favor thrombolysis. These mechanisms may contribute to the reduction in myocardial ischemia and clinical events observed with lipid lowering in patients with vascular disease. Lipid-lowering therapy decreases cardiovascular events and is an important adjunct to coronary revascularization most likely because an improvement in endothelial function prevents the development and destabilization of new atherosclerotic lesions and subsequent ischemic events.

Anticholesteremic Agents↗

PubMed2005

Endothelial function in patients with vasculogenic erectile dysfunction.

OBJECTIVES: Erectile dysfunction (ED) commonly coexists with coronary artery disease (CAD) and/or risk factors for atherosclerosis. Because the silent or documented atherosclerosis or vascular risk factors are very frequent, the possibility of endothelial dysfunction in ED patients is expected to be increased. Our aim was to evaluate the endothelial functions in patients with vasculogenic ED with vascular risk factors and compare them with age-matched non-ED patients or healthy controls. DESIGN: We studied 36 patients with presumed vasculogenic ED, 39 age-matched patients with similar risk factors without ED and 25 age-matched healthy controls without ED, known cardiovascular disease or risk factors. Erectile function was evaluated by the International Index of Erectile Dysfunction (IIEF) scores. Brachial artery flow-mediated dilatation (FMD) and nitroglycerine-mediated dilatation (NMD) were measured. RESULTS: Baseline demographics were similar except the IIEF score and duration of diabetes in patients with ED. Brachial artery FMD and NMD were significantly reduced in patients with ED (3.2+/-3. vs. 6+/-4, p<0.0001 for FMD, 12.2+/-6 vs. 15.4+/-6 p=0.032 for NMD). In patients with similar risk factors but without ED, FMD was significantly lower but NMD were not different compared with healthy controls (6+/-4 vs. 10.2+/-3, p<0.0001 for FMD and 15.4+/-8 vs. 16.4+/-6, p=0.81). IIEF scores were weakly correlated with FMD (r=0.25, p=0.028) in patients with ED. There were significant correlations between FMD and NMD in patients with ED (r=0.46, p=0.05) and with risk factors (r=0.72, p<0.0001) but not in healthy controls (r=0.54, p=0.792). Vasculogenic ED patients have more markedly impaired endothelial and smooth muscle functions compared with patients with similar risk factors but no ED.

Arteriosclerosis↗

PubMed1996

Time course of endothelial function in epicardial conduit coronary arteries and in the microcirculation in the long-term follow-up after cardiac transplantation.

BACKGROUND: Endothelial dysfunction has been reported in epicardial conduit coronary arteries and in the microcirculation after cardiac transplantation. It has been assumed that endothelial dysfunction may precede hemodynamically relevant transplant vasculopathy. In this study the long-term course of endothelial function was investigated in conduit coronary arteries and in the microcirculation after cardiac transplantation. METHODS: Patients were stratified according to time after transplantation (group I, up to 2 years after transplantation; group II, 2 to 4 years after transplantation; group III, more than 4 years after transplantation). Changes of the diameter of proximal, mid and distal segments of the left anterior descending coronary artery and the circumflex branch of the left coronary artery were investigated after endothelium-dependent and endothelium-independent stimulation with acetylcholine (ACh, 50 and 100 micrograms i.c.) and nitroglycerin 0.3 mg i.c. Coronary flow changes were assessed endothelium-dependently (ACh 50 and 100 micrograms i.c.) and endothelium-independently (dipyridamole 0.56 mg/kg i.v.) utilizing an 8 F Judkins-style Doppler catheter. RESULTS: Application of 50 micrograms/100 micrograms ACh resulted in a reduction of coronary artery diameter in proximal, mid and distal vascular segments of the left anterior descending coronary artery and the circumflex branch of the left coronary artery. The vasoconstrictive effect did not differ significantly between groups I,II and III. Nitroglycerin 0.3 mg i.c. increased coronary artery diameters in groups I, II and III. ACh (50 micrograms/100 micrograms) increased coronary flow index by 217 +/- 70%/236 +/- 110% (P < 0.05 vs. baseline) in group I, 113 +/- 26%/77 +/- 22% (P < 0.05 vs. baseline) in group II and 108 +/- 26%/109 +/- 21% (P < 0.05 vs. baseline) in group III. Dipyridamole increased coronary flow index by 296 +/- 78% (P < 0.05 vs. baseline) in group I, by 63 +/- 16% (P < 0.05 vs. baseline and vs. group I) in group II and by 113 +/- 30% (P < 0.05 vs. baseline and vs. group I) in group III. CONCLUSION: A constant vasosonstrictor response to ACh was observed in epicardial coronary arteries after cardiac transplantation indicating endothelial dysfunction independent of the time course. Endothelial dysfunction in these vessels may not be an early indicator of hemodynamically relevant transplant vasculopathy. Endothelium-dependent and endothelium-independent flow reserves decreased 2 years after transplantation and remained constant thereafter.

Acetylcholine↗

PubMed2006

Effect of interaction between left ventricular dysfunction and endothelial function in hypertension.

Hypertension, one of the most important risk factors for cardiovascular diseases, is associated with both left ventricular hypertrophy and endothelial dysfunction. Both have been recently recognized as independent predictors of clinical events in different groups of patients. In fact, a dysfunctioning endothelium loses its antiatherosclerotic and antithrombotic action, and, therefore, promotes the atherosclerotic process. Similarly, cardiac hypertrophy is recognized as a powerful and independent risk factor for cardiovascular morbidity and mortality because it predisposes to arrhythmias and maximizes the consequences of acute myocardial ischemia. Recently, an evident interaction has been demonstrated between endothelial dysfunction and left ventricular mass. In particular, the coexistence of both left ventricular hypertrophy and endothelial dysfunction almost doubles the risk for future vascular events in hypertensives. Thus, in hypertensive patients, it is clinically useful to choose an aggressive therapeutic strategy--to reduce left ventricular mass and to improve endothelial function.

Coronary Artery Disease↗

PubMed2006

Association of coronary shear stress with endothelial function and vascular remodeling in patients with normal or mildly diseased coronary arteries.

BACKGROUND: The relationship between coronary remodeling, shear stress and endothelial function remains unclear. OBJECTIVE: The present study investigated the effects of mechanical factors on structure and function of epicardial coronary arteries. METHODS: Patients (group 1: %area stenosis<40%, n=55; or group 2: %area stenosis>or=40%, n=17) with a discrete mildly stenotic lesion (%diameter stenosis<30%) underwent intravascular ultrasound examination of the left anterior descending coronary artery for determination of vessel area, lumen area, plaque area, cross-sectional areas at reference segments, and remodeling index (the ratio of vessel area at the culprit lesion to vessel area at the proximal reference site). Further, vascular reactivity was examined using intracoronary administration of acetylcholine, papaverine, and nitroglycerin. RESULTS: Vessel area significantly correlated with plaque area in both groups (r=0.65, P<0.0001 and r=0.85, P<0.0001). Group 1 showed significantly greater acetylcholine-induced percentage changes in coronary blood flow (67+/-70 vs. 16+/-75%, P<0.05) and coronary artery diameter (-7+/-18 vs.-32+/-31%, P<0.01) and also significantly smaller coronary wall shear stress (65+/-27 vs. 81+/-32 dynes/cm, P<0.05) than group 2. The percentage increase in coronary blood flow induced by acetylcholine was significantly and positively correlated with remodeling index in group 1 (r=0.64, P<0.0001) but not in group 2 (r=-0.03, P=0.90) and was also significantly and positively correlated with coronary wall shear stress in group 1 (r=0.46, P<0.001) but not in group 2 (r=-0.33, P=0.19). CONCLUSIONS: Endothelium-dependent vasodilation in the resistance coronary artery correlates with remodeling via increased wall shear stress when target lesions %area stenosis is <40%.

Adult↗

PubMed1995

Endothelial function in spontaneously hypertensive rats: influence of quinapril treatment.

1. Angiotensin converting enzyme (ACE) inhibition has been shown to restore the impaired endothelial function in hypertension, but the mediators underlying the promoted endothelium-dependent dilatation have not been fully characterized. Therefore, we investigated the effects of 10-week-long quinapril therapy (10 mg kg-1 day-1) on responses of mesenteric arterial rings in vitro from spontaneously hypertensive rats (SHR) and normotensive Wistar-Kyoto (WKY) rats. 2. Endothelium-dependent relaxations of noradrenaline (NA)-precontracted rings to acetylcholine (ACh) and adenosine 5'-diphosphate (ADP) were similar in WKY rats and quinapril-treated SHR and more pronounced than in untreated SHR. The nitric oxide (NO) synthase inhibitor NG-nitro-L-arginine methyl ester (L-NAME) attenuated the relaxations in both WKY groups and quinapril-treated SHR, and completely inhibited them in untreated SHR. When endothelium-dependent hyperpolarization was prevented by precontraction of the preparations with potassium chloride (KCl), no differences were found in relaxations to ACh and ADP between the study groups. In addition, in NA-precontracted rings the L-NAME- and indomethacin-resistant relaxations to ACh were partially prevented by apamin, an inhibitor of calcium-activated potassium channels. 3. Interestingly, in quinapril-treated SHR but not in the other groups, exogenous bradykinin potentiated the relaxations to ACh in both NA- and KCl-precontracted arterial rings. 4. Contractile sensitivity of endothelium-intact rings to NA was reduced in SHR by quinapril, and was more effectively increased by L-NAME in quinapril-treated than untreated SHR. 5. In conclusion, since the relaxations to ACh and ADP in quinapril-treated SHR were augmented in the absence and presence of NO synthesis inhibition but not under conditions which prevented hyperpolarization, enhanced endothelium-dependent relaxation after long-term ACE inhibition can be attributed to increased endothelium-dependent hyperpolarization. However, the potentiation of the response to ACh by exogenous bradykinin in quinapril-treated SHR, as well as the increased attenuating effect of the endothelium on NA-induced contractions in these animals appear to result from enhanced endothelium-derived NO release.

Aging↗

PubMed1997

The long-term effect of captopril treatment on endothelial function in spontaneously hypertensive rats.

The aim of this study is to elucidate the long term effect of captopril treatment on the endothelial function to release nitric oxide (NO) in spontaneously hypertensive rats (SHR). The properties of endothelium were determined with a model of hindquarter perfusion in response to alpha 1 adrenergic agonist, phenylephrine, at the age of 40 weeks of SHR which was administrated with captopril (100 mg/kg/day) from intrauterine and withdrawn at 16 weeks of age. Furthermore, in the presence of N omega-nitro-L-arginine methyl ester (LNAME), or L-arginine, the responses to phenylephrine were studied. From the curve of perfusion pressure, the minimal, maximal perfusion pressure (PPmin, PPmax) and the maximal slope (slope), as well as the 50% of effective concentration (EC50) were obtained. The data show that in captopril treated SHR, PPmin, PPmax and slope were markedly lower, but EC50 higher than those of untreated SHR. The curve induced by phenylephrine was significantly right shift compared with that of untreated SHR. Like WKY, the intensive reactivity to phenylephrine in the presence of LNAME was much lower than that of untreated SHR. In the presence of L-arginine, however, the right shift of curves was seen only in captopril treated SHR and WKY rats, but not in control SHR. In conclusion, endothelium does involve in the response of resistant vessel to phenylephrine. The mechanism of enhanced reactivity in untreated SHR may be, at least in part, due to the diminished capacity of producing NO from endothelium, and the effect of sustained hypotension of early captopril treatment might be relevant to the improved ability of endothelium.

Angiotensin-Converting Enzyme Inhibitors↗

PubMed2001

Blood pressure, endothelial function and circulating endothelin concentrations in liver transplant recipients.

OBJECTIVES: To study candidates for liver transplant before and 6 weeks after transplant, and to elucidate the role of endothelial dysfunction and plasma endothelin concentrations in the development of hypertension. DESIGN PROSPECTIVE: follow-up study. SETTING: Institutional, outpatient. PATIENTS: and controls Fifteen patients (11 men, four women, mean age 46.7+/-13.2 years) with end-stage liver disease (ESLD) and healthy volunteers of comparable age and sex. METHODS: We performed office blood pressure readings and 24 h ambulatory blood pressure monitoring (ABPM), measurements of endothelial-dependent vasodilatation using high-resolution ultrasound in the brachial artery at rest and during reactive hyperemia, and plasma endothelin-1 assays 3 months before and 6 weeks after the transplant. RESULTS: Office systolic and diastolic blood pressures increased significantly 6 weeks after liver transplantation (from 116.6+/-14.1 to 139.9+/-19.5 mmHg and from 68.6+/-9.5 to 84.1+/-9.8 mmHg, respectively; both P < 0.001). Hypertension based on office blood pressure readings increased from 6.7 to 40% (P < 0.05). Mean 24 h systolic blood pressure increased from 118.7+/-10.3 to 140.0+/-19.0 mmHg (P < 0.001), mean 24 h diastolic blood pressure increased from 86.0+/-7.7 to 104.8+/-13.9 mmHg (P < 0.001) and heart rate increased from 74.8+/-10.2 to 80.2+/-8.2 beats/min (P < 0.05). Brachial artery flow-mediated dilatation did not change throughout the study (before transplant: 4.2+/-4.0%; after transplant: 6.3+/-5.4%; NS) and did not differ from that in controls (5.2+/-3.8%). Plasma endothelin-1 was increased in patients with ESLD (15.3+/-2.6 pg/ml) compared with controls (5.6+/-0.4 pg/ ml; P < 0.001) and remained unchanged 6 weeks after liver transplantation (14.1+/-3.7 pg/ml). CONCLUSION: Our results show increased blood pressure with suppressed circadian blood pressure variability in liver graft recipients 6 weeks after transplant and no change in endothelial function and plasma endothelin concentrations. Therefore, the blood pressure increase documented in our study cannot be explained by endothelial dysfunction. Twenty-four hour ABPM should be performed routinely in patients who have undergone liver transplant.

Adult↗

PubMed2001

Expression of endomyocardial nitric oxide synthase and coronary endothelial function in human cardiac allografts.

BACKGROUND: Inducible nitric oxide synthase (iNOS) is expressed and is functionally active in the presence of transplant arteriosclerosis. However, the early involvement of iNOS in alterations of microvascular endothelial function in the absence of preexisting lesions remains unclear; this information would be of prognostic value. We studied the course of iNOS mRNA expression, transcardiac nitric oxide production, and their potential association with microvascular coronary endothelial dysfunction in human cardiac allografts. METHODS AND RESULTS: A total of 42 patients were studied at 1, 6, and 12 months after heart transplantation. Microvascular coronary flow velocity reserve (CFVR) was tested in an endothelium-dependent (acetylcholine) and -independent manner (adenosine) using a Doppler flow wire. Endomyocardial iNOS expression was determined by reverse transcription polymerase chain reaction. iNOS protein and nitrotyrosine levels were detected by immunohistochemistry. Transcardiac plasma nitrite/nitrate (NOx) levels were measured by the Griess reaction. CFVR was impaired in 26.1% of patients (n=11) at 1 month and in 31% of patients (n=13) at 12 months after heart transplantation. Patients who developed impaired CFVR in the first year showed a significant increase in iNOS gene expression. Patients with impairment of CFVR 1 month after heart transplantation had higher levels of iNOS mRNA than patients with a normal CFVR. Patients with an initial impairment of CFVR who did not improve over time presented with significantly higher iNOS mRNA levels. iNOS protein and nitrotyrosine were expressed in the endomyocardial vessels of patients with impaired CFVR. Transcardiac NOx release was higher in patients with impaired CFVR. CONCLUSIONS: In human cardiac allografts, microvascular endothelial dysfunction is associated with an enhanced endomyocardial iNOS mRNA expression and higher transcardiac NOx production and is accompanied by the expression of nitrotyrosine protein, suggesting peroxynitrite plays a role in the disease process. The data from the present study suggest an important role for the iNOS/nitric oxide pathway in the regulation of microvascular function in the absence of preexisting atherosclerotic lesions.

Acetylcholine↗

PubMed1995

Changes of endothelial functions in the coronary artery after chronic nitroarginine feeding.

1. The effects of chronic NG-nitro-L-arginine (LNA) feeding on the endothelial function in isolated coronary arteries from stroke-prone spontaneously hypertensive rats (SHRSP) and normotensive Wistar-Kyoto (WKY) rats were studied. 2. A diet containing LNA (0.02%) was given to male SHRSP and WKY at 6 weeks of age and the coronary arteries were dissected on the 10th day of feeding. 3. In the SHRSP and WKY fed the LNA-free diet, acetylcholine (ACh) relaxed the precontracted ring segments of the coronary artery with intact endothelium in a dose-dependent manner. The reactivity was stronger in the WKY than in the SHRSP. However, the ACh-induced relaxation after the LNA-feeding was significantly stronger in the coronary arteries from the WKY than in those from the SHRSP. 4. The relaxation induced by the calcitonin gene-related peptide (CGRP) was endothelium-dependent and endothelium-independent. The degree of the response in the rats fed the LNA-containing diet was not significantly different from that in the rats fed the LNA-free diet. 5. The vasodilator response induced by sodium nitroprusside (SNP) was dose-dependent and similar in the rats fed the LNA containing diet and the LNA-free diet. 6. These findings indicate that chronic LNA feeding markedly impaired the endothelial nitric oxide formation in the coronary artery from young SHRSP.

Animals↗

PubMed2001

Impairment of endothelial function after a high-fat meal in patients with coronary artery disease.

OBJECTIVE: To determine the effect of postprandial lipid changes on endothelial function in patients with coronary artery disease (CAD) after a high-fat meal. METHODS: We studied 50 CAD patients and 25 control participants, who were all normocholesterolemic. Flow-mediated vasodilatation of the brachial artery was evaluated by the high-resolution ultrasound technique before and after a single high-fat meal (800 calories; 50 g fat). RESULTS: Postprandial serum triglyceride level increased significantly at 2-7 h and mean flow-mediated vasodilatation was impaired significantly (from 4.22 +/- 0.44 to 2.75 +/- 0.33%, P < 0.01) for 75 subjects. The increment in 2 h serum triglyceride level correlated positively with the decrement in postprandial flow-mediated vasodilatation (r = 0.459, P < 0.01). Postprandial triglyceride level was significantly higher in CAD patients than in control participants. Flow-mediated vasodilatation was significantly impaired in CAD patients (from 3.04 +/- 0.39 to 1.69 +/- 0.23%, P < 0.01) and control participants (from 6.58 +/- 0.52 to 4.87 +/- 0.19%, P < 0.05) after a high-fat meal. The impairment of flow-mediated dilatation was more severe in CAD patients (44.41%) than in control participants (25.99%, P < 0.01). CONCLUSION: Postprandial endothelium-dependent vasodilatation after a single high-fat meal was severely impaired in normocholesterolemic CAD patients and control participants. The disordered postprandial metabolism of triglyceride-rich lipoproteins may play an atherogenic role by inducing endothelial dysfunction.

Adult↗

PubMed2001

A placebo-controlled trial of long-term oral combined continuous hormone replacement therapy in postmenopausal women: effects on arterial compliance and endothelial function.

OBJECTIVE: To study the effects of long-term combined continuous oral hormone replacement therapy (HRT) on vascular function in healthy postmenopausal women. BACKGROUND: The cardiovascular effects of HRT are controversial. Improvement in vascular function is a proposed mechanism of oestrogen action but there are no long-term controlled human trials in this area. In this study, we examined the effects of HRT on lipid profiles and vascular function, encompassing both biomechanical arterial properties [systemic arterial compliance (SAC) and pulse wave velocity (PWV)] and endothelial function [flow-mediated vasodilation (FMD)]. METHODS: In this 2-year, double-blind, placebo-controlled study, 59 healthy postmenopausal women were randomized to oral combined continuous oestrogen and progesterone [Kliogest, oestradiol (2 mg), norethisterone (1 mg)] or placebo, with end-points measured at baseline, 6 weeks and after 6,12 and 24 months of treatment. RESULTS: Oral combined HRT reduced lipoprotein a [Lp(a)], although other lipid benefits were not observed. There were no significant changes in SAC, PWV or FMD with oral combined HRT, compared to placebo. CONCLUSION: In this long-term, randomized placebo-controlled trial, oral continuous HRT with combined oestradiol and norethisterone in healthy postmenopausal women did not improve a spectrum of indices of arterial function compared to placebo. These results suggest that HRT might not be of cardiovascular benefit in postmenopausal women.

Analysis of Variance↗

PubMed2003

3.5 years of insulin therapy with insulin glargine improves in vivo endothelial function in type 2 diabetes.

OBJECTIVE: To determine long-term effects of insulin glargine on vascular function in patients with type 2 diabetes. METHODS AND RESULTS: A total of 49 in vivo endothelial function tests, intrabrachial artery infusions of endothelium-dependent (acetylcholine [ACh]) and endothelium-independent (sodium nitroprusside [SNP]) vasoactive agents, were performed in 11 patients with type 2 diabetes (age: 59+/-2 years; BMI: 29.7+/-0.9 kg/m2; fasting plasma glucose: 226+/-14 mg/dL) and 16 matched normal subjects. The tests in the type 2 diabetic patients were performed before and after 6 months and 3.5 years of combination therapy with insulin glargine and metformin. A control group of type 2 diabetic patients not treated with insulin was studied twice at 6-month intervals. Before treatment, blood flow during infusions of low and high doses of ACh were significantly lower in the type 2 diabetic patients than in the normal subjects (P=0.021 for ANOVA). In the patients with type 2 diabetes, blood flow during infusion of the low dose of ACh averaged 7.1+/-0.8 mL/dL per minute at baseline, 8.8+/-1.0 mL/dL per minute at 6 months (NS), and then increased compared with baseline by 87+/-29% to 11.6+/-1.4 mL/dL per minute at 3.5 years (P<0.02 versus baseline). Blood flow during infusion of the high dose of ACh increased from 8.8+/-0.9 at baseline to 13.0+/-1.9 mL/dL per minute at 6 months (P<0.05) and by 86+/-25% to 14.7+/-1.6 mL/dL per minute at 3.5 years (P<0.01 versus baseline), which was not different from normal subjects. Blood flow during infusion of low (blood flow at 0 months: 7.7+/-0.5; at 6 months: 9.9+/-0.6; P<0.01 for 6 versus 0 months; and 3.5 years: 11.6+/-1.1 mL/dL per minute; P<0.02 for 3.5 years versus 0 months) and high (blood flow at 0 months: 10.7+/-0.9; 6 months: 13.4+/-1.0; P<0.05 for 6 versus 0 months; and 3.5 years: 16.6+/-1.5 mL/dL per minute; P<0.05 for 3.5 years versus 0 months) doses of SNP also increased significantly during insulin therapy. CONCLUSIONS: We conclude that insulin glargine therapy improves endothelium-dependent and endothelium-independent vasodilatation. These data support the idea that long-term insulin therapy has beneficial rather than harmful effects on vascular function in type 2 diabetes.

Acetylcholine↗

PubMed2002

Effect of lowering tumour necrosis factor-alpha on vascular endothelial function in Type II diabetes.

Tumour necrosis factor-alpha (TNF alpha) is a mediator of reactive oxygen species, which are implicated in endothelial dysfunction and atherosclerosis. Type II diabetes is associated with endothelial dysfunction and elevated circulating TNF alpha. We hypothesized that reducing serum levels of TNFalpha, using pentoxifylline, would improve endothelial function. Thirteen subjects [age 58+/-2 (S.E.M.) years] with Type II diabetes (disease duration 74+/-13 months) undertook a randomized, crossover study of 8 weeks pentoxifylline and 8 weeks placebo. Endothelium-dependent and-independent vasodilation in resistance arteries was assessed via bilateral forearm venous occlusion plethysmography during intra-brachial infusions of acetylcholine (ACh), sodium nitroprusside (SNP) and N(G)-monomethyl-L-arginine (L-NMMA). High-resolution ultrasound of the brachial artery in response to ischaemia was used to determine endothelium-dependent conduit vessel flow-mediated dilation (FMD), and endothelium-independent conduit function was assessed by sublingual administration of glyceryl trinitrate (GTN). Serum concentrations of TNF alpha were also determined. Pentoxifylline lowered serum TNF alpha from 4.1+/-0.7 to 2.9+/-0.6 pg x ml(-1) (P=0.001). Forearm blood flow (FBF) responses at each dose of ACh did not differ with treatment (P=0.4). Similarly, FBF responses to SNP (P=0.8) and L-NMMA (P=0.2) did not differ. There was also no significant difference in brachial artery diameter during FMD (P=0.2) or GTN administration (P=0.06). Despite lowering serum TNF alpha concentration, pentoxifylline at a dose of 400 mg three times a day for 8 weeks did not improve vascular function in either conduit or resistance vessels in this group of Type II diabetic subjects.

Acetylcholine↗

PubMed2003

Effects of fenofibrate on endothelial function and cell adhesion molecules during post-prandial lipemia in hypertriglyceridemia.

BACKGROUND: Fasting and post-prandial hypertriglyceridemia have been associated with endothelial dysfunction. OBJECTIVE: To investigate the effects of a 3-month treatment with fenofibrate (200 mg daily) on endothelial reactivity and inflammatory state in hypertriglyceridemic patients at fast and after an oral fat load. METHODS: Brachial flow-mediated vasodilation (FMV) and the circulating levels of intercellular adhesion molecule (ICAM) and vascular cellular adhesion molecule (VCAM) were determined in 10 hypertriglyceridemic patients. RESULTS: Before treatment, post-prandial phase was characterized by an increase in triglycerides (3.7 +/- 1 mmol/L at baseline vs. 4.2 +/- 1, 6.5 +/- 1, 6.6 +/- 2, and 5.3 +/- 2 mmol/L after 2, 4, 6, and 8 h), a decrease in FMV (4.3 +/- 2% at baseline vs. 2.8 +/- 1, 2.2 +/- 1, and 1.3 +/- 1% after 2, 4, and 6 h), and an increase in ICAM and VCAM. After fenofibrate there was a significant reduction in fasting triglycerides (3.7 +/- 1.3 vs. 2.1 +/- 0.8 mmol/L), ICAM (480 +/- 113 vs. 269 +/- 65 ng/mL) and VCAM (1821 +/- 570 vs. 1104 +/- 376 ng/mL), and an increase in FMV (4.3 +/- 2 vs. 7.1 +/- 2%). Post-prandially triglycerides increased (2.1 +/- 1 at baseline vs. 2.4 +/- 2 and 3.6 +/- 1 mmol/L after 4 and 6 h), FMV decreased (7.1 +/- 2 at baseline vs. 5.8 +/- 2, 5.5 +/- 2, 5.9 +/- 2, 6.4 +/- 2% after 2, 4, 6, and 8 h), and there was an increase of ICAM and VCAM. Before therapy post-prandial changes in FMV had an inverse correlation with the changes in triglycerides (r = -0.34; P < 0.05) and ICAM (r = -0.66; P < 0.001). CONCLUSIONS: The transient endothelial dysfunction observed in hypertriglyceridemic subjects during post-prandial lipemia is mediated by post-prandial triglyceride increase and by the activation of inflammatory response. The anti-inflammatory activity of fenofibrate may represent an additional mechanism of its favorable action on the endothelial function during fasting and the post-prandial phase.

Adult↗