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Results for “endothelial dysfunction”

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At least 721 records · Page 40Linked to original sources

PubMed1999

Peripheral endothelial dysfunction in normal pressure glaucoma.

PURPOSE: To assess vascular endothelial function in patients with normal pressure glaucoma using forearm blood flow responses to intra-arterial infusions of endothelial-dependent and -independent vasoactive agents. METHODS: Eight patients with newly diagnosed and untreated normal pressure glaucoma and eight healthy age- and sex-matched control volunteers underwent measurement of forearm blood flow using venous occlusion plethysmography. Blood flow was assessed in response to incremental doses of sodium nitroprusside (an endothelial-independent vasodilator), acetylcholine (an endothelial-dependent vasodilator) and the vasoconstrictor N(G)-monomethyl-L-arginine (an inhibitor of nitric oxide synthase). RESULTS: Sodium nitroprusside caused a dose-related increase in forearm blood flow in patients and controls. Glaucoma patients appeared to have an increased vasodilatory response, but this was not significant (P = 0.23). Acetylcholine also induced vasodilatation in both groups, but the response was significantly reduced in the glaucoma group (P = 0.04). N(G)-monomethyl-L-arginine induced a similar degree of vasoconstriction in both groups (P = 0.76). CONCLUSIONS: This study has shown an impairment of peripheral endothelium-mediated vasodilatation in normal pressure glaucoma. These findings would support the concept of a generalized vascular endothelial dysfunction in patients with this condition.

Acetylcholine↗

PubMed2005

Excessive stimulation of poly(ADP-ribosyl)ation contributes to endothelial dysfunction in pre-eclampsia.

1. Pre-eclampsia is a serious pregnancy disorder associated with widespread activation of the maternal vascular endothelium. Recent evidence implicates a role for oxidative stress in the aetiology of this condition. 2. Reactive oxygen species, particularly superoxide anions, invokes endothelial cell activation through many pathways. Oxidant-induced cell injury triggers the activation of nuclear enzyme poly(ADP-ribose) polymerase (PARP) leading to endothelial dysfunction in various pathophysiological conditions (reperfusion, shock, diabetes). 3. We have studied whether the loss of endothelial function in pre-eclampsia is dependent on PARP activity. Endothelium-dependent responses of myometrial arteries were tested following exposure to either plasma from women with pre-eclampsia or normal pregnant women in the presence and absence of a novel potent inhibitor of PARP, PJ34. Additional effects of plasma and PJ34 inhibition were identified in microvascular endothelial cell cultures. 4. In myometrial arteries, PARP inhibition blocked the attenuation of endothelium-dependent responses following exposure to plasma from women with pre-eclampsia. In endothelial cell cultures, plasma from pre-eclamptics induced measurable oxidative stress and a concomitant increase in PARP activity and reduction in cellular ATP. Again, these biochemical changes were reversed by PJ34. 5. These results suggest that PARP activity plays a pathogenic role in the development of endothelial dysfunction in pre-eclampsia and promotes PARP inhibition as a potential therapy in this condition.

Adenosine Triphosphate↗

PubMed2005

Increased expression of iNOS is associated with endothelial dysfunction and impaired pressor responsiveness in streptozotocin-induced diabetes.

Studies in streptozotocin (STZ)-induced diabetic rats have demonstrated cardiovascular abnormalities such as depressed mean arterial blood pressure (MABP) and heart rate (HR), endothelial dysfunction, and attenuated pressor responses to vasoactive agents. We investigated whether these abnormalities are due to diabetes-associated activation of inducible nitric oxide synthase (iNOS). In addition, the effect of the duration of diabetes on these abnormalities was also evaluated. Diabetes was induced by administration of 60 mg/kg STZ via the tail vein. One, 3, 9, or 12 wk after STZ injection, MABP, HR, and endothelial function were measured in conscious unrestrained rats. Pressor response curves to bolus doses of methoxamine (MTX) and angiotensin II (ANG II) were constructed in the presence of N-[3(aminomethyl)benzyl]-acetamidine, dihydrochloride (1400W), a specific inhibitor of iNOS. Depressed MABP and HR and impairment of endothelial function were observed as early as 3 wk after induction of diabetes. Acute inhibition of iNOS with 1400W (3 mg/kg i.v.) restored the attenuated pressor responses to both MTX and ANG II without affecting the basal MABP and HR. Immunohistochemical and Western analysis blot studies in cardiovascular tissues revealed decreased expression of endothelial nitric oxide synthase (eNOS) concomitant with increased expression of iNOS and nitrotyrosine with the progression of diabetes. Our findings suggest that induction of iNOS in cardiovascular tissues is dependent on the duration of diabetes and contributes significantly to the depressed pressor responses to vasoactive agents and potentially to endothelial dysfunction.

Amidines↗

PubMed2001

Mechanism of endothelial dysfunction in apolipoprotein E-deficient mice.

Endothelium-dependent relaxations mediated by NO are impaired in a mouse model of human atherosclerosis. Our objective was to characterize the mechanisms underlying endothelial dysfunction in aortas of apolipoprotein E (apoE)-deficient mice, treated for 26 to 29 weeks with a lipid-rich Western-type diet. Aortic rings from apoE-deficient mice showed impaired endothelium-dependent relaxations to acetylcholine (10(-)(9) to 10(-)(5) mol/L) and Ca(2+) ionophore (10(-)(9) to 10(-)(6) mol/L) and endothelium-independent relaxations to diethylammonium (Z)-1-(N,N-diethylamino)diazen-1-ium-1,2-diolate (DEA-NONOate, 10(-)(10) to 10(-)(5) mol/L) compared with aortic rings from C57BL/6J mice (P<0.05). By use of confocal microscopy of an oxidative fluorescent probe (dihydroethidium), increased superoxide anion (O(2)(-)) production was demonstrated throughout the aortic wall but mainly in smooth muscle cells of apoE-deficient mice. CuZn-superoxide dismutase (SOD) and Mn-SOD protein expressions were unaltered in the aorta exposed to hypercholesterolemia. A cell-permeable SOD mimetic, Mn(III) tetra(4-benzoic acid) porphyrin chloride (10(-)(5) mol/L), reduced O(2)(-) production and partially normalized relaxations to acetylcholine and DEA-NONOate in apoE-deficient mice (P<0.05). [(14)C]L-Citrulline assay showed a decrease of Ca(2+)-dependent NOS activity in aortas from apoE-deficient mice compared with C57BL/6J mice (P<0.05), whereas NO synthase protein expression was unchanged. In addition, cGMP levels were significantly reduced in the aortas of apoE-deficient mice (P<0.05). Our results demonstrate that in apoE-deficient mice on a Western-type fat diet, impairment of endothelial function is caused by increased production of O(2)(-) and reduced endothelial NO synthase enzyme activity. Thus, chemical inactivation of NO with O(2)(-) and reduced biosynthesis of NO are key mechanisms responsible for endothelial dysfunction in aortas of atherosclerotic apoE-deficient mice.

Animals↗

PubMed1998

The role of adenosine and ATP-sensitive potassium channels in the protection afforded by ischemic preconditioning against the post-ischemic endothelial dysfunction in guinea-pig hearts.

The role of adenosine and ATP-sensitive potassium channels (KATP) in the mechanism of ischemic preconditioning (IPC)-induced protection against the post-ischemic endothelial dysfunction was studied. Langendorff-perfused guinea-pig hearts were subjected either to 40 min of global ischemia and 40 min reperfusion or were preconditioned prior to the ischemia/reperfusion with three cycles of either 5 min ischemia/5 min reperfusion (IPC) or 5 min infusion/5 min wash-out of adenosine, adenosine A1 receptor agonist, N6-cyclohexyladenosine (CHA) or KATP opener, pinacidil. The magnitude of coronary flow reduction caused by NO-synthase inhibitor, Nomega-nitro-l-arginine methyl ester (l-NAME), served as an index of a basal endothelium-dependent vasodilator tone. Coronary overflows produced by a bolus of acetylcholine (ACh) and sodium nitroprusside (SNP) were used as measures of agonist-induced endothelium-dependent and endothelium-independent vascular function, respectively. The coronary flow, LVDP, ACh response and l-NAME response were reduced by 8, 32, 41 and 54%, respectively, while SNP response was not changed in the hearts subjected to ischemia/reperfusion. ACh response was fully restored, l-NAME response was partially restored, and SNP response was not affected in the hearts subjected to IPC. The post-ischemic recoveries of coronary flow and LVDP were not improved by IPC. The protective effect of IPC on the ACh response was mimicked by adenosine, CHA, and pinacidil. The protective effect of IPC, CHA and pinacidil was abolished by KATP antagonist, glibenclamide. The IPC protection was affected neither by a non-specific adenosine antagonist, 8-p-sulfophenyltheophylline, nor by a specific adenosine A1 receptor antagonist, 8-cyclopentyl-1, 3-dipropylxanthine (DPCPX). Our data indicate that: (1) IPC affords endothelial protection in the mechanism that involves activation of KATP, but not adenosine A1 receptors; (2) exogenous adenosine and A1 receptor agonist afford the protection, which might be of a potential clinical significance; (3) the endothelial dysfunction is not involved in the mechanism of myocardial stunning in guinea-pig hearts.

Acetylcholine↗

PubMed2002

Evidence for an independent and cumulative effect of postprandial hypertriglyceridemia and hyperglycemia on endothelial dysfunction and oxidative stress generation: effects of short- and long-term simvastatin treatment.

BACKGROUND: Postprandial hypertriglyceridemia and hyperglycemia are considered risk factors for cardiovascular disease. Evidence suggests that postprandial hypertriglyceridemia and hyperglycemia induce endothelial dysfunction through oxidative stress; however, the distinct role of these two factors is a matter of debate. METHODS AND RESULTS: Thirty type 2 diabetic patients and 20 normal subjects ate 3 different meals: a high-fat meal; 75 g glucose alone; and high-fat meal plus glucose. Glycemia, triglyceridemia, nitrotyrosine, and endothelial function were assayed during the tests. Subsequently, diabetics took 40 mg/d simvastatin or placebo for 12 weeks. The 3 tests were performed again at baseline, between 3 to 6 days after the start, and at the end of each study. High-fat load and glucose alone produced a decrease of endothelial function and an increase of nitrotyrosine in normal and diabetic subjects. These effects were more pronounced when high fat and glucose were combined. Short-term simvastatin treatment had no effect on lipid parameters but reduced the effect on endothelial function and nitrotyrosine observed during each different test. Long-term simvastatin treatment was accompanied by a lower increase in postprandial triglycerides, which was followed by smaller variations of endothelial function and nitrotyrosine during the tests. CONCLUSIONS: This study shows an independent and cumulative effect of postprandial hypertriglyceridemia and hyperglycemia on endothelial function, suggesting oxidative stress as common mediator of such effect. Simvastatin shows a beneficial effect on oxidative stress and endothelial dysfunction, which may be ascribed to a direct effect as well as the lipid-lowering action of the drug.

Blood Glucose↗

PubMed2005

[The protective effects of Radix Astragali and Rhizoma Ligustici chuanxiong on endothelial dysfunction in type 2 diabetic patients with microalbuminuria].

OBJECTIVE: To evaluate the effects of traditional Chinese complex prescription of Radix Astragali and Rhizoma Ligustici Chuanxiong on urinary albumin excretion (UAE) and vascular endothelial dysfunction in type 2 diabetic patients with microalbuminuria. METHODS: Twenty-one type 2 diabetic patients with microalbuminuria were involved in this before-after study by individual informed consent. Each of the eligible subjects was given the decoction of Radix Astragali and Rhizoma Ligustici Chuanxiong per os 150 ml q.d. for six months. The following examinations were performed at baseline and after treatment: (1) high-resolution ultrasonography to measure the diameter changes of brachial artery in response to reactive hyperemia (endothelium-dependent) and on administration of glyceryl trinitrate (endothelium-independent); (2) high resolution ultrasonography to measure combined intima-media thickness (IMT) of common carotid arteries (CCA); (3) fasting plasma plasminogen activator inhibitor type 1 (PAI-1) activity, C reactive protein (CRP) and malonic aldehyde(MDA) concentration. RESULTS: The patients had impaired endothelial dependent vasodilation (EDV), elevated plasma PAI-1 activity and increased CRP and MDA concentration at baseline. After six months treatment with Radix Astragali and Rhizoma Ligustici Chuanxiong, their urinary albumin-to- creatinine ratio decreased from (86.5 +/- 53.9) microg/mg to (55.05 +/- 51.67) microg/mg (P=0.002). The EDV was improved at the end of the treatment (baseline: 7.49 +/- 2.98%, after treatment: 12.73 +/- 5.36%, P=0.001). Meanwhile, the activity of PAI-1 and the levels of MDA and CRP were significantly decreased CPAI-1: (83.49 +/- 5.11) X 10(-2) AU/ml vs. (79.7 +/- 7.8) x 10(-2) AU/ml, P=0.015; MDA: (3.20 +/- 1.13) nmol/L vs. (2.09 +/- 0.71) nmol/L, P=0.000; CRP: (7.04 +/- 2.64) mg/ L vs. (1.58 +/- 0.69) mg/L, P=0.000]. But no significant changes of the CCA IMT and endothelial independent vasodilation (EIV) were observed. Partial correlated analysis showed that MDA concentration was negatively correlated with EDV (r=-0.3736, P = 0.018). Correlated analysis also showed that CRP was negatively correlated with EDV (r=-0.348, P=0.028). CONCLUSION: Radix Astragali and Rhizoma Ligustici Chuanxiong compound medication may decrease urinary albumin excretion and improve endothelial dysfunction in type 2 diabetic patients with microalbuminuria. The mechanism may relate with the therapeutic effects of Radix Astragali and Rhizoma Ligustici Chuanxiong on anti-inflammation, anti-oxidation and alleviation of the hypo-fibrinolytic/pro-thrombotic state.

Adult↗

PubMed2002

Endothelial dysfunction in aging animals: the role of poly(ADP-ribose) polymerase activation.

Recent work has demonstrated the production of reactive oxygen and nitrogen species in the vasculature of aging animals. Oxidant induced cell injury triggers the activation of nuclear enzyme poly(ADP ribose) polymerase (PARP) leading to endothelial dysfunction in various pathophysiological conditions (reperfusion, shock, diabetes). Here we studied whether the loss of endothelial function in aging rats is dependent upon the PARP pathway within the vasculature. Young (3 months-old) and aging (22 months-old) Wistar rats were treated for 2 months with vehicle or the PARP inhibitor PJ34. In the vehicle-treated aging animals there was a significant loss of endothelial function, as measured by the relaxant responsiveness of vascular rings to acetylcholine. Treatment with PJ34, a potent PARP inhibitor, restored normal endothelial function. There was no impairment of the contractile function and endothelium-independent vasodilatation in aging rats. Furthermore, we found no deterioration in the myocardial contractile function in aging animals. Thus, intraendothelial PARP activation may contribute to endothelial dysfunction associated with aging.

Aging↗

PubMed2004

Endothelial dysfunction and mild renal insufficiency in essential hypertension.

BACKGROUND: Mild to moderate renal insufficiency in individuals with essential hypertension is currently considered the expression of a renal microvasculopathy characterized by preglomerular arteriolar involvement and tubulo-interstitial changes. Whether endothelial dysfunction plays a role in this alteration is still undefined. METHODS AND RESULTS: We investigated the relationship between endothelial function (hemodynamic response to acetylcholine [ACh] in the forearm) and renal function in 500 patients with uncomplicated, never-treated, essential hypertension and serum creatinine within the normal range (ie, < or =1.5 mg/dL). Serum creatinine, creatinine clearance, and estimated glomerular filtration rate (GFR, by the Modification of Diet in Renal Disease formula) were related to the forearm blood flow response to ACh (all P< or =0.003), and these relationships held true in multiple regression analyses that included age, gender, systolic pressure, serum cholesterol and glucose, smoking, and body mass index. Accordingly, on multiple logistic regression analysis, the risk of moderate renal dysfunction (ie, an estimated GFR <60 mL x min(-1) x 1.73 m(-2)) was 64% lower (OR 0.36, 95% CI 0.18 to 0.70) in patients in the third ACh tertile (ie, those showing the higher vasodilatory response) than in those in the first tertile (ie, showing the lower response). C-reactive protein was related directly to serum creatinine and inversely to GFR and vasodilatory response to ACh, which suggests that endothelial dysfunction is a possible mechanism linking inflammation and impaired renal function in essential hypertension. CONCLUSIONS: An impaired vasodilatory response to ACh appears to be associated with renal function loss in patients with essential hypertension. This association suggests that systemic endothelial dysfunction is involved in mild to moderate renal insufficiency in patients with uncomplicated essential hypertension.

Acetylcholine↗

PubMed2003

Association between coronary endothelial dysfunction and local inflammation of atherosclerotic coronary arteries.

We have examined a possibility whether or not severity and extent of coronary atherosclerosis may associate with degree of local inflammation in relation to endothelial dysfunction as is indicated by reduced NO formation. Blood samples were obtained from aortic root (Ao) and coronary sinus (CS) of 39 patients who underwent coronary angiography. Plasma NOx levels (nitrite + nitrate, stable NO end-products) were evaluated by HPLC-Griess system, and markers of inflammation, C-reactive protein (CRP) and serum amyloid A protein (SAA), were measured by Latex Turbidimetric Immunoassay. To evaluate the changes of these substances through coronary circulation, the percentage changes of respective markers [(CS - Ao) x 100/Ao] were calculated. The extent and severity of atherosclerosis of left coronary arteries were evaluated with Gensini Score (GS). The GS correlated with the percentage changes of NOx (r = -0.35, p < 0.05) and that of SAA (r = 0.43, p < 0.05) across coronary circulation, but not with changes in CRP. Moreover, the percentage changes of NOx correlated with that of SAA (r = -0.36, p < 0.05). These results indicated that severity and extent of coronary atherosclerosis related to degree of local inflammation which has a possible association with coronary endothelial dysfunction.

Biomarkers↗

PubMed1998

Endothelial dysfunction precedes hypertension in diet-induced insulin resistance.

The insulin-resistant (IR) syndrome may be an impetus for the development of hypertension (HTN). Unfortunately, the mechanism by which this could occur is unclear. Our laboratory and others have described impaired endothelium-mediated relaxation in IR, mildly hypertensive rats. The purpose of the current study is to determine if HTN is most likely a cause or result of impaired endothelial function. Sprague-Dawley rats were randomized to receive a fructose-rich diet for 3, 7, 10, 14, 18, or 28 days or were placed in a control group. The control group received rat chow. After diet treatment, animals were instrumented with arterial cannulas, and while awake and unrestrained, their blood pressure (BP) was measured. Subsequently, endothelium-mediated relaxation to acetylcholine was determined (in vitro) by measuring intraluminal diameter of phenylephrine-preconstricted mesenteric arteries ( approximately 250 microM). Serum insulin levels were significantly elevated in all groups receiving fructose feeding compared with control, whereas there were no differences in serum glucose levels between groups. Impairment of endothelium-mediated relaxation starts by day 14 [mean percent maximal relaxation (Emax): 69 +/- 10% of baseline] and becomes significant by day 18 (Emax: 52 +/- 11% of baseline; P < 0.01). However, the mean BP (mmHg) does not become significantly elevated until day 28 [BP: 132 +/- 1 (day 28) vs. 116 +/- 3 (control); P < 0.05]. These findings demonstrate that both IR and endothelial dysfunction occur before HTN in this model and suggest that endothelial dysfunction may be a mechanism linking insulin resistance and essential HTN.

Animals↗

PubMed1998

[Endothelial dysfunction: a global response].

The endothelium is a dynamic organ involved in the genesis and development of the cardiovascular diseases. Nitric oxide (NO) is one of the factors released from endothelium. NO is generated by endothelial cells through the activity of a constitutive nitric oxide synthase (cNOS). Smooth muscle cells generate NO by an inducible NOS isoform (iNOS). NO regulates vascular tone, different mechanisms involved in the interaction of blood cells to the vascular wall, the growth of smooth muscle cells and the matrix protein synthesis. The lack of an endothelium-dependent vasodilatory response has been defined as endothelial dysfunction. It has been demonstrated a reduced endothelium-dependent vasodilation response in hypertension, aging, atherosclerosis ... and in patients without evident coronary disease. Although the cNOS has been initially described as constitutive, in recent years it has been demonstrated that several pathophysiological stimuli such as hypoxia, chronic exercise, cytokines regulate its level of expression. Our laboratory has demonstrated that an endothelial cytosolic protein regulates the half-lives of eNOS mRNA. This endothelial cytosolic protein could be a target for specific drugs to prevent endothelial dysfunction.

Endothelium, Vascular↗

PubMed2004

Vascular insulin response is preserved in non-diabetic patients with coronary artery disease, despite endothelial dysfunction.

BACKGROUND: Patients with coronary artery disease (CAD) are often insulin resistant, a state that predisposes to increased atherosclerosis. Recently, it was suggested that a "vascular insulin resistance" could explain this association, causing endothelial dysfunction and hence atherosclerosis. We therefore studied the vascular insulin response in patients with CAD. MATERIALS AND METHODS: Nine non-diabetic patients with documented CAD and 31 lean healthy controls were examined. Forearm blood flow was measured by venous occlusion plethysmography. Dose-response studies of acetylcholine (ACh) and sodium nitroprusside (SNP) elicited endothelium-dependent and -independent vasodilation and were repeated during intra-arterial insulin infusion. RESULTS: Patients were insulin resistant as determined by HOMA index. Insulin infusion resulted in high physiological levels of insulin in the forearm without systemic effects. Patients had a reduced ACh response but insulin infusion increased the ACh response equally in patients and controls (a mean increase of 74+/-37 vs 57+/-24%, patients vs controls, p=0.12). A minor increase of the SNP response was also noted during insulin infusion. CONCLUSION: Vascular insulin response is intact in non-diabetic CAD patients in spite of insulin resistance and endothelial dysfunction.

Acetylcholine↗

PubMed1989

Radiation-induced endothelial dysfunction and fibrosis in rat lung: modification by the angiotensin converting enzyme inhibitor CL242817.

The purpose of this study was to evaluate the angiotensin converting enzyme (ACE) inhibitor CL242817 as a modifier of radiation-induced pulmonary endothelial dysfunction and pulmonary fibrosis in rats sacrificed 2 months after a single dose of 60Co gamma rays (0-30 Gy) to the right hemithorax. CL242817 was administered in the feed continuously after irradiation at a regimen of 60 mg/kg/day. Pulmonary endothelial function was monitored by lung ACE activity, plasminogen activator (PLA) activity, and prostacyclin (PGI2) and thromboxane (TXA2) production. Pulmonary fibrosis was evaluated by lung hydroxyproline (HP) content. Lung ACE and PLA activities decreased with increasing radiation dose, and cotreatment with CL242817 significantly ameliorated both responses. CL242817 dose-reduction factors (DRF) were 1.3-1.5 for ACE and PLA activity. Lung PGI2 and TXA2 production increased with increasing radiation dose, and CL242817 almost completely prevented both radiation responses. The slope of the radiation dose-response curves in the CL242817-treated rats was essentially zero, precluding calculation of DRF values for PGI2 and TXA2 production. Lung HP content also increased with increasing radiation dose, and CL242817 significantly attenuated this response (DRF = 1.5). These data suggest that the ability of ACE inhibitors to ameliorate radiation-induced pulmonary endothelial dysfunction is not unique to captopril [Ward et al., Int. J. Radiat. Oncol. Biol. Phys. 15, 135-140 (1988)], rather it is a therapeutic action shared by other members of this class of compounds. These data also provide the first evidence that ACE inhibitors exhibit antifibrotic activity in irradiated rat lung.

Angiotensin-Converting Enzyme Inhibitors↗

PubMed1996

Chronic treatment in vivo with dimethylthiourea, a hydroxyl radical scavenger, prevents diabetes-induced endothelial dysfunction.

Oxidative stress is believed to play a role in diabetes-induced vascular complications. In this study, we tested whether chronic treatment with a known hydroxyl radical scavenger, dimethylthiourea (DMTU), could prevent endothelial dysfunction in diabetes. Lewis strain rats were made diabetic by an intravenous injection of streptozotocin. A subgroup of diabetic animals received daily intraperitoneal injections of 50 mg/kg DMTU beginning at 72 h after streptozotocin and throughout 8 weeks of diabetes. Diabetes caused an increase in aortic catalase activity (an index of compensatory in vivo oxidative stress) that was not prevented by long-term DMTU treatment. Long-term treatment of diabetic animals with DMTU did not alter serum insulin levels, blood glucose concentrations, or total glycosylated hemoglobin. Descending thoracic aortas were isolated, sectioned into rings and suspended in isolated tissue baths, and contracted with a submaximal concentration of norepinephrine. Relaxation to the endothelium-dependent vasodilator, acetylcholine, was impaired in diabetic aortas, whereas relaxation to A23187 and nitroglycerin was unaltered. DMTU treatment prevented the diabetes-induced impairment in endothelium-dependent relaxation to acetylcholine but had no effect on relaxations induced by either A23187 or nitroglycerin. These data suggest that chronic exposure to increased levels of hydroxyl radicals in vivo likely play a significant role in the origin of diabetes-associated endothelial dysfunction.

Acetylcholine↗

PubMed2005

Association of Helicobacter pylori infection with systemic inflammation and endothelial dysfunction in healthy male subjects.

OBJECTIVES: The goal of the present study was to determine whether seropositivity to Helicobacter pylori (HP), Chlamydia pneumoniae (CP), and cytomegalovirus (CMV) is associated with systemic inflammation and endothelial dysfunction in healthy male subjects. BACKGROUND: Chronic infection with certain bacteria and viruses may play an important role in inflammation as the pathogenesis of atherosclerosis. METHODS: The serum levels of immunoglobulin G antibodies to HP, CP, CMV, high-sensitivity C-reactive protein, soluble intercellular adhesion molecule-1, and soluble vascular cell adhesion molecule-1 were determined in 81 healthy Japanese men (40 +/- 10 years of age). High-frequency ultrasonographic imaging of the brachial artery was used to study endothelium-dependent (flow-mediated vasodilation) and endothelium-independent (nitroglycerin-induced) vasodilation. RESULTS: Prevalences of seropositive antibodies to HP, CP, and CMV were 67.9%, 61.7%, and 56.8%, respectively. Infection with HP, CP, or CMV had no relationship with age, blood pressure, or level of serum glucose, lipid, or soluble vascular cell adhesion molecule-1. The levels of C-reactive protein and soluble intercellular adhesion molecule-1 were significantly higher, and flow-mediated vasodilation was significantly lower in subjects with seropositive antibodies to HP than in subjects with seronegative antibodies to HP. Endothelium-independent vasodilation was similar in both groups. CONCLUSIONS: Chronic infection with HP may be involved in the development of the atherosclerosis via endothelial dysfunction and systemic and vascular inflammation.

Adult↗

PubMed2003

Endothelial dysfunction in young patients with long-term rheumatoid arthritis and low disease activity.

OBJECTIVE: Cardiovascular mortality is excessive in patients with rheumatoid arthritis (RA). It has been proposed that the chronic inflammatory state of RA contributes to accelerated atherosclerosis. The aim of this study was to determine whether endothelial dysfunction, an early sign of arteriosclerosis, is present in young, long-term RA patients receiving standard methotrexate (MTX) therapy. Furthermore, we tested whether etanercept (ENC), a TNF-alpha receptor blocker, resulted in improved endothelial function compared to MTX in the same patients. METHODS: We studied eight RA patients twice: (1) on MTX and (2) after MTX washout and receiving ENC. Eight healthy volunteers matching for age, gender, height, weight and conventional cardiovascular risk factors served as control (C). All participants received intrabrachial infusions of increasing doses of acetylcholine (ACh, endothelium-dependent vasodilator) and glyceryl-trinitrate (GTN, endothelium-independent vasodilator). Forearm blood flow (FBF) was measured by bilateral venous occlusion plethysmography. RESULTS: Disease activity of RA was comparably low during both MTX and ENC (DAS 28 3.9+/-0.3 and 3.5+/-0.3). FBF in response to ACh was reduced in RA compared to C (P<0.01). Switching from MTX to ENC failed to improve vascular responsiveness to ACh. GTN comparably increased FBF in all groups. CONCLUSIONS: Our study for the first time demonstrates that long-term RA is associated with manifested endothelial dysfunction. Switching from MTX to ENC in stable RA patients has no beneficial effect on endothelial function.

Acetylcholine↗

PubMed2004

Statins and endothelial dysfunction.

The endothelium integrates and modulates critical functions of the arterial wall. As well as regulating vasomotion, it controls inflammation, coagulation, and thrombosis. Many of these actions are mediated through the release of nitric oxide. Endothelial dysfunction is associated with atherosclerosis and its risk factors. It is independently correlated to adverse cardiovascular events, including myocardial infarction, coronary death, and the need for revascularization. 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitors (statins) protect against cardiovascular death, myocardial ischemia, myocardial infarction, and stroke. Although cholesterol reduction accounts for some of these benefits, others appear to be independent of cholesterol lowering. The endothelium mediates many of these "lipid-dependent" and "lipid-independent" actions of statins. This chapter reviews the effects of statins on endothelial dysfunction. To do so, a brief outline of the biology of the endothelium is a prerequisite. This will be followed by a summary of the advances in vascular research on cholesterol-dependent and cholesterol-independent effects of statins, with a focus on the endothelium. Ultimately, clinical relevance of observations derived from basic biology will be discussed.

Arteriosclerosis↗