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Results for “endothelial dysfunction”

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PubMed1998

von Willebrand factor and urinary albumin excretion are possible indicators of endothelial dysfunction in cardiopulmonary bypass.

OBJECTIVE: Experimental evidence suggests that cardiopulmonary bypass (CPB) associated inflammatory response leads to endothelial injury and increased permeability, but this has been difficult to show clinically. We have investigated the use of von Willebrand factor (vWF), and urinary albumin excretion, as measured by the urinary albumin creatinine ratio (ACR), to demonstrate this. METHODS: A total of 23 patients undergoing elective coronary artery bypass grafting were studied. Complement fragment C3a, leukotrienne B4 (LTB4), interleukin 6 (IL6), neutrophil elastase, vWF and ACR were measured on anaesthetic induction (baseline), 20 min after starting CPB, 5 min after cross-clamp removal, 5 min, 2, 6 and 24 h after termination of CPB. Anaesthetic, CPB and myocardial protection techniques were standardised. ANOVA was performed by using the distribution free Friedman test for each measured parameter. When significance differences were found (P < 0.05), post hoc analysis with Wilcoxon signed rank test was used for comparison of each time point with the base line level and differences were only accepted as significant following the Bonferroni correction (P < 0.008). Summary measures of peak versus peak and area under the cure were also analysed for ACR with vWF. RESULTS: Peak vs. baseline levels for C3a were 4.9 vs. 2.1 microg/ml (P < 0.0001), LTB4 was 800 vs. 20 pg/ml (P < 0.0001), neutrophil elastase was 250 vs. 115 ng/ml (P < 0.001), IL6 was 620 vs. 1.4 pg/ml (P < 0.0001), vWF was 2.2 vs. 1.3 IU/ml (P < 0.0001) and ACR was 17.6 vs. 2.0 mg/mmol (P < 0.0001). C3a, LTB4 and ACR peaked during the operation. Neutrophil elastase peaked at 2 h following CPB. IL6 and vWF peaked at 6 h following CPB. The correlation coefficient between vWF and ACR following peak versus peak analysis was 0.48 (P = 0.035), and area under the curve analysis was 0.6 (P < 0.01). CONCLUSION: These results demonstrate that endothelial permeability and injury, as measured by urinary albumin excretion and vWF, respectively, are related and the use of these easily detectable and sensitive biochemical markers warrants further investigation.

Aged↗

PubMed2006

Inflammation as a mediator of the link between mild to moderate renal insufficiency and endothelial dysfunction in essential hypertension.

The relationship among inflammation (plasma high-sensitivity C-reactive protein [CRP]), endothelial function (hemodynamic response to acetylcholine [ACh] in the forearm), and renal function (serum creatinine and GFR [Modification of Diet in Renal Disease formula]) was investigated in 264 never-treated individuals with uncomplicated essential hypertension and serum creatinine within the normal range. Multiple regression models of renal function (creatinine) were constructed in sequence including Framingham risk factors as well the hemodynamic response to ACh and plasma CRP. The inclusion of endothelial function into a model based on Framingham risk factors added highly significant (P < 0.001) power to this model (+5%). Of note, in an alternative model that included CRP (instead of endothelial function), the creatinine variance explained by this factor was two times higher (+10%) than that associated with endothelial function in the first model. In the full model that included both endothelial function and CRP, CRP maintained a much stronger independent link with the outcome measure than endothelial function. In individuals with untreated, uncomplicated essential hypertension, multivariate modeling indicated that inflammation is a crucial mechanism mediating the endothelial-renal function link. The proatherogenic potential of inflammation associated with subtle impairment in renal function may contribute to the cardiovascular risk of essential hypertension.

Acetylcholine↗

PubMed2006

Influence of nebivolol on endothelial dysfunction in salt-sensitive hypertension.

The study was aimed to assess influence of nebivolol (nebilet) on endothelial factors (NO and endothelin1) during treatment of salt-sensitive hypertensive patients. A total of 40 patients (18 females and 22 males, mean age 53,1+/-1,58 yrs) with mild (I stage) arterial hypertension (with diastolic pressure 90-99 mm Hg and/or systolic pressure 140-159 mm Hg) were studied. Twelve age matched healthy subjects (4 women and 8 males) composed control group. Salt sensitivity was detected by M. Weir (1993) method. Patients were divided in two groups: salt sensitive hypertension (group I, 16 patients) and salt-resistant hypertension (group II, 24 patients). Nebivolol (Nebilet, Berlin-Chemie, Germany) was administered to 25 patients in dosage of 5 mg once a day during two weeks. Our studies have showed that ET-1 plasma levels were significantly elevated in patients with essential hypertension, while NO was markedly reduced compared to control group. NO levels were slightly lower in salt-sensitive hypertensives than in salt-resistant patients (p>0,05). ET-1 levels expressed opposite changes: in patients with salt-sensitive hypertension ET-1 levels almost twice exceeded those of salt-resistant patients (p<0,01). After treatment with nebivolol NO plasma level in salt-sensitive hypertensives significantly increased in Group I and did not change significantly in salt-resistant patients. Only slight decrease in ET-1 levels was detected in both groups after taking nebilet. Nebilet (nebivolol) treatment has an influence only on NO levels and appears to be the most effective in salt-sensitive hypertension.

Benzopyrans↗

PubMedDate not supplied

Assessment of endothelial dysfunction: focus on atherothrombotic disease.

As the endothelium is crucial to cardiovascular disease, the accurate assessment of this organ is a valuable tool, especially if such assessments are clinically relevant. As functions of the endothelium focus on haemostasis and the maintenance of correct vascular tone, and dysfunction results in changes that promote thrombosis and hypertension, thus assessment of endothelial function therefore follows these processes. Foremost in the plasma markers of vascular function is von Willebrand factor, a molecule that interacts with platelets. Lack of nitric oxide results in poor blood pressure control that can be quantified by impaired flow mediated dilatation. More recently, increased numbers of circulating endothelial cells have been described that indicate severe damage to the endothelium. Unsurprisingly, these three markers correlate with each other and former two predict adverse outcome in long-term follow up studies. The assessment of vascular damage is becoming recognised as having an increasingly prominent part in the pathophysiology of cardiovascular disease.

Endothelium, Vascular↗

PubMed1996

Endothelial dysfunction late after Kawasaki disease.

BACKGROUND: Kawasaki disease (KD) is a systemic vasculitis of childhood with widespread vascular endothelial damage in the acute stage. Long-term complications, such as myocardial infarction and death, are recognized, but the extent and nature of late vascular abnormalities that might predispose to these events have not been studied. METHODS AND RESULTS: We used high-resolution ultrasound to study endothelial function in the brachial artery of 20 patients 5 to 17 years after acute KD (median, 11 years) and compared findings with those in 20 age- and sex-matched control subjects. Vascular responses to reactive hyperemia (with flow increase leading to endothelium-dependent dilation) and to sublingual glyceryl trinitrate (GTN; endothelium-independent dilation) were recorded. The relationship between endothelium-dependent vascular responses and features of the endothelium acute illness was examined. There was no difference in baseline vessel diameter, degree of reactive hyperemia, or response to GTN between patients and control subjects. In contrast, flow-mediated dilation was markedly reduced in KD patients compared with control subjects (3.1% versus 9.4%; P < .001). Late endothelium-dependent responses were not related to features of the acute illness. CONCLUSIONS: Abnormalities of systemic endothelial function are present many years after resolution of acute KD, even in patients without detectable early coronary artery involvement. Because this may be an important factor in the genesis of late vascular complications, long-term follow-up of all patients with KD is indicated.

Adolescent↗

PubMed2002

Endothelial dysfunction and blood pressure variability in selected inbred mouse strains.

The genetic regulation of blood pressure (BP) and endothelial function is likely to be polygenic. Because there is considerable variability in basal BP among inbred mouse strains, the purpose of this study was to determine whether a similar variability in vascular function exists among 7 "normotensive" strains. We tested the hypothesis that compared with mice with higher BPs, mice with lower BPs would have greater aortic endothelial responses to acetylcholine (ACh). Mean BP ranged from 117 to 145 mm Hg among the 7 strains. The responses of aortic rings to ACh, sodium nitroprusside, and papaverine were assessed after submaximal precontraction with prostaglandin F(2alpha). The aortas from all strains relaxed in a concentration-dependent manner to sodium nitroprusside and papaverine, but responses to ACh were markedly impaired in the aortas, but not carotid arteries, from 129P3/J and 129X1/SvJ mice. Aortas from the other strains relaxed normally to ACh. Furthermore, the endothelium-dependent dilators ADP and A23187 caused similar relaxation in 129P3/J, 129X1/SvJ, and C57BL/6J mice. Although the data do not support the initial hypothesis, the impaired aortic response to ACh in the 129 strains is a novel finding and illustrates the potential impact that genetic background can have on vascular responsiveness.

Acetylcholine↗

PubMed2001

Dysfunctional endothelial nitric oxide biosynthesis in healthy smokers with impaired endothelium-dependent vasodilatation.

BACKGROUND: The mechanisms involved in the dysfunction of both endothelium-dependent vasodilatation (EDV) and NO biosynthesis related to smoking are unclear. In this study, EDV was assessed in healthy smokers and nonsmokers in vivo and, using serum from the same individuals, was related to the NO biosynthetic pathway in vitro. METHODS AND RESULTS: Flow-mediated EDV of the brachial artery was measured in 23 male patients (8 nonsmokers and 15 smokers). Serum was collected, added to confluent ( approximately 85%) monolayers of human umbilical vein endothelial cells (HUVECs), and incubated for 12 hours. Basal and substance P-stimulated NO production was measured. The HUVECs used for measuring basal NO production were lysed, and both endothelial NO synthase (eNOS) protein expression and eNOS activity were determined. EDV was lower in smokers compared with nonsmokers (P<0.001). HUVECs treated with serum from smokers compared with nonsmokers showed significantly lower basal (P<0.0001) and stimulated (P<0.02) NO production, higher eNOS expression (P<0.0001), but lower eNOS activity (P<0.004). There was a significant positive correlation between in vivo EDV and in vitro substance P-stimulated NO production (rho=0.57, P<0.01) and between basal NO production and eNOS activity (r=0.54, P<0.008) and a negative correlation between basal NO production and eNOS protein expression (r=-0.60, P<0.003). CONCLUIONS: This is the first study to combine an in vivo model with a near-physiological in vitro model to demonstrate an association between decreased NO production and reduced EDV. Cigarette smoking was associated with reduced EDV, NO generation, and eNOS activity in the presence of increased eNOS protein expression.

Adult↗

PubMed2001

Improvement in endothelial dysfunction in patients with hypoalphalipoproteinemia and coronary artery disease treated with bezafibrate.

Isolated low high-density lipoprotein cholesterol (HDLc) is a well-known risk factor for cardiovascular disease and is associated with arterial endothelium dysfunction. Several studies have shown that cholesterol lowering in patients with hypercholesterolemia improves endothelial function, but the effect of treating low HDLc levels remains unknown. We studied the effect of increasing HDLc on endothelial function in patients with coronary artery disease (CAD) and isolated low HDLc (HDLc) <0.91 mM, low-density lipoprotein cholesterol (LDLc) <4.1 mM, and triglycerides <2.8 mM. Flow-mediated endothelium-dependent dilatation (FMD) in response to reactive hyperemia was measured by brachial ultrasound, before and after bezafibrate treatment (400 mg daily for 6 months) in 16 patients with CAD and impaired FMD (<10%). After bezafibrate therapy, HDLc increased from 0.79-1.0 mM (p = 0.0008) at the expense of both HDL2 and HDL3 subfractions, apolipoprotein A-I increased from 1.04-1.19 g/l (p = 0.0012), and fibrinogen decreased from 4.45-3.39 g/l (p = 0.0007). The impaired FMD increased after bezafibrate treatment from a median of 2.5-12.3% (p = 0.0004). Endothelial function was normalized in eight patients (50%), improved in four (25%), and did not change in four (25%). These observations indicate that in patients with isolated low HDLc and CAD, bezafibrate treatment improves endothelial function of brachial arteries, increases HDLc and apolipoprotein A-I, and lowers fibrinogen concentrations.

Aged↗

PubMed1999

L-arginine attenuates endothelial dysfunction in endotoxin-induced lung injury.

BACKGROUND: Pulmonary vasorelaxation to endothelium-dependent and independent agonists is dysfunctional in endotoxin-induced acute lung injury. L-arginine is the precursor to endothelial production of nitric oxide (NO), suggesting that arginine and NO are intimately linked. We hypothesized that L-arginine would attenuate endotoxin-induced dysfunction of guanosine 3',5'-cyclic monophosphate-mediated pulmonary vasorelaxation. METHODS: Concentration-response curves were generated for acetylcholine, calcium ionophore A23187, and sodium nitroprusside (SNP) in isolated phenylepherine-preconstricted pulmonary artery rings (10(-9) to 10(-6) mol/L) 4 hours after endotoxin (500 mg/kg intraperitoneal) or saline injection. The effect of L-arginine in vitro was determined with L- or D-arginine (50 mmol/L) 30 minutes before dose response. RESULTS: Endothelium-dependent pulmonary vasorelaxation was dysfunctional after endotoxin injection as demonstrated by impaired responses to acetylcholine and A23187 (P < .05 vs control). Endotoxin-induced dysfunction of these endothelium-dependent responses was attenuated by L-arginine (P < .05 vs endotoxin). Endothelium-independent vasorelaxation (SNP) was also dysfunctional after endotoxin treatment (P < .05 vs control). L-arginine failed to attenuate the endotoxin-induced dysfunction of the response to SNP. The concentration responses for endothelium-dependent and independent vasorelaxing agonists in endotoxin-treated rats were not influenced by D-arginine. CONCLUSION: L-arginine supplementation attenuates endotoxin-induced dysfunction of endothelium-dependent pulmonary vasorelaxation.

Acetylcholine↗

PubMed2005

Soluble factors released by placental villous tissue: Interleukin-1 is a potential mediator of endothelial dysfunction.

OBJECTIVE: The purpose of this study was to analyze the potential of placental-conditioned medium to activate endothelial cells in vitro and to identify the placental factors that mediate this effect. STUDY DESIGN: Placental-conditioned medium was generated by the culturing of normal term placental villous explants for up to 48 hours. Human umbilical vein endothelial cells were exposed to the conditioned media, and cellular proliferation, viability, and activation were investigated. RESULTS: The proliferation of endothelial cells that were exposed to 20% placental-conditioned medium was reduced by 25%, but their survival was not compromised. Conditioned medium also up-regulated the expression of E-selectin and stimulated the release of soluble intercellular adhesion molecule-1 and the secretion of interleukin-6. Treatment with interleukin-1 receptor antagonist, but not with an anti-tumor necrosis factor-alpha neutralizing antibody, blocked the release of soluble intercellular adhesion molecule-1 and interleukin-6. CONCLUSION: Placentally derived interleukin-1 may be 1 of the potential mediators of the maternal inflammatory response that is observed in late pregnancy.

Cell Proliferation↗

PubMed2000

Endothelial dysfunction after repeated Chlamydia pneumoniae infection in apolipoprotein E-knockout mice.

BACKGROUND: Arterial relaxation is largely regulated by endothelial nitric oxide (NO). Its diminished activity has been associated with incipient atherosclerosis. We investigated the endothelium-dependent relaxation of aorta in apolipoprotein E-knockout (apoE-KO) mice exposed to single or repeated Chlamydia pneumoniae inoculation. METHODS AND RESULTS: Forty-eight apoE-KO mice, 8 weeks old, were inoculated intranasally with C pneumoniae (n=24) or saline (n=24) every 2 weeks over a 6-week period. Twenty mice (10 infected and 10 controls) were killed at 2 weeks and 6 weeks, respectively, after the first inoculation. The smooth muscle tone of aortic rings was measured in vitro at both time points. The norepinephrine-precontracted thoracic aortic rings were successively exposed to methacholine in the absence and presence of N:(G)-nitro-L-arginine methyl ester (L-NAME) and diclofenac. The methacholine-induced relaxation was attenuated in the infected mice at 6 weeks in both the absence and presence of L-NAME (P:<0.05 and P:<0.01, respectively). When administered together with L-NAME, diclofenac enhanced the relaxation of the L-NAME-pretreated aortas in infected mice at 2 weeks (P:<0.05) but not in noninfected mice. The relaxation response from infected mice tended to differ in the same manner at 6 weeks (P:<0.1). No intimal thickening was detected at either time point. CONCLUSIONS: C pneumoniae impairs arterial endothelial function, and the NO pathway is principally involved. Cyclooxygenase-dependent vasoconstricting products may also account for the infection-induced impaired relaxation. These findings further support the role of C pneumoniae infection in atherosclerosis development.

Alkaline Phosphatase↗

PubMed1993

[Endothelial dysfunction and coronary heart disease. Interaction of endothelium and thrombocytes].

Aggregating thrombocytes release various mediators acting on endothelium and muscle cells of coronary arteries. In coronary arteries without endothelium, platelets induce potent vasoconstriction, whereas in segments with endothelium platelets induce relaxation. This endothelium-dependent relaxation induced by platelets is caused by the endothelial relaxation factor EDRF or nitric oxide (NO). NO inhibits not only smooth muscle cells of the vessels but also platelets themselves, an effect which is potentiated by prostacyclin. The physiologic importance of platelets-mediated contraction after removal of the vascular endothelium concerns the vascular phase of hemostasis. With the appearance of functional endothelial disorders, particularly in patients with cardiovascular risk factors, disturbances of coronary circulation can arise and finally cause ischemia. The finding that regenerated endothelial cells show functional defects especially towards the action of platelets (mainly the serotonin released from platelets) is important. In this functional disorder a dysfunction of Gi-protein of the endothelial 5HT1-serotonergic receptor plays a decisive role. Similar functional endothelial disorders can be shown after ischemia and reperfusion as well as in arteriosclerosis.

Animals↗

PubMed2004

Endothelial dysfunction and reactive oxygen species production in ischemia/reperfusion and nitrate tolerance.

Reactive oxygen species (ROS), as superoxide and its metabolites, have important roles in vascular homeostasis as they are involved in various signaling processes. In many cardiovascular disease states, however, the release of ROS is increased. Uncontrolled ROS production leads to impaired endothelial function and consequently to vascular dysfunction. This review focuses on two clinical conditions associated with elevated ROS levels: ischemia/reperfusion and nitrate tolerance. Injury caused by ischemia/reperfusion is an important limitation of transplantations, and complicates the management of stroke and myocardial infarction. Nitrates, which are used to treat transient myocardial ischemia (angina pectoris), decrease in efficacy in long-term continuous administration. There are several enzyme systems, such as xanthine oxidase, cyclooxygenase, uncoupled endothelial nitric oxide synthase, NAD(P)H oxidase, cytochrome P450 and the mitochondrial electron transport chain, which are responsible for the increased vascular production of superoxide. The contribution of particular ROS producing enzymes and the effect of antioxidant treatment are discussed in both pathological conditions.

Animals↗

PubMed1998

Hydralazine prevents endothelial dysfunction, but not the increase in superoxide production in nitric oxide-deficient hypertension.

Dilator responses, superoxide anion-production, endothelial nitric oxide (NO) synthase and soluble guanylyl cyclase expression were determined in aortic rings from Wistar rats treated for 5 weeks either with the NO synthase inhibitor NG-nitro-L-arginine-methylester (L-NAME), L-NAME plus hydralazine or placebo. In the L-NAME-treated group, acetylcholine-induced relaxation was significantly attenuated whereas it was nearly normal in the L-NAME/hydralazine group. This difference was even more pronounced following inhibition of the endogenous superoxide dismutase using diethyldithiocarbamate. Aortic superoxide production was significantly elevated in both L-NAME-treated groups and hydralazine had no acute effect on superoxide formation. Expression of endothelial NO synthase was similar in all three groups whereas the attenuated soluble guanylyl cyclase expression in rats treated with L-NAME was nearly normalised by concomitant hydralazine treatment. These results demonstrate that in NO-deficient hypertension hydralazine treatment improves vasodilator responses but not the increased superoxide production.

Acetylcholine↗

PubMed2001

Protective effect of heme oxygenase-1 gene transfer against oxyhemoglobin-induced endothelial dysfunction.

The current study was designed to determine the effect of recombinant heme oxygenase-1 (HO-1) gene expression on endothelial function in cerebral arteries. Isolated canine basilar arteries were exposed ex vivo (30 minutes at 37 degrees C) to an adenoviral vector (10(10) PFU/mL, total volume 300 microL) encoding either the HO-1 gene (AdCMVHO-1) or the beta-galactosidase (beta-Gal) reporter gene (AdCMVbeta-Gal). Twenty-four hours after transduction, arterial rings were suspended in organ chamber for isometric force recording. Endothelium-dependent relaxations were obtained in response to bradykinin (10(-10) to 10(-6) mol/L) during contraction to uridine-5'-triphosphate (UTP; 3 x 10(-6) to 3 x 10(-5) mol/L). Certain rings were incubated with oxyhemoglobin (OxyHb; 10(-5) mol/L) overnight (16 to 18 hours of 24 hours). Expression and localization of recombinant protein were shown by Western blot analysis and immunohistochemistry. Endothelium-dependent relaxation to bradykinin and endothelium-independent relaxation to forskolin (10(-9) to 10(-5) mol/L) and DEA-NONOate (10(-10) to 10(-5) mol/L) were identical in beta-Gal- and HO-1-transduced arteries. Exposure to OxyHb caused impairment of endothelium-dependent relaxation to bradykinin (P < 0.01). In contrast, OxyHb did not affect endothelium-dependent relaxation in arteries expressing recombinant HO-1 ( P > 0.05). This protective effect of HO-1 was reversed by coincubation with tin protoporphyrin (SnPP9; 10(-5) mol/L), a selective inhibitor of HO-1 (P < 0.01). Basal levels of 3',5'-cyclic monophosphate (cGMP) in HO-1-transduced vessels were not significantly different from those in beta-Gal-transduced vessels. Pretreatment with OxyHb significantly reduced cGMP level in beta-Gal-transduced rings (P < 0.01), whereas it had no effect in HO-1-transduced rings. These results demonstrate that HO-1 gene transfer does not affect endothelial and smooth muscle function of normal arteries, and that expression of recombinant HO-1 in cerebral arteries protects vasomotor function against OxyHb-induced injury.

Animals↗

PubMed2005

Phosphodiesterase type 5 inhibition does not reverse endothelial dysfunction in patients with coronary heart disease.

OBJECTIVES: To investigate whether sildenafil citrate, a selective phosphodiesterase type 5 inhibitor, may improve endothelial vasomotor and fibrinolytic function in patients with coronary heart disease. DESIGN: Randomised double blind placebo controlled crossover study. PATIENTS AND METHODS: 16 male patients with coronary heart disease and eight matched healthy men received intravenous sildenafil or placebo. Bilateral forearm blood flow and fibrinolytic parameters were measured by venous occlusion plethysmography and blood sampling in response to intrabrachial infusions of acetylcholine, substance P, sodium nitroprusside, and verapamil. MAIN OUTCOME MEASURES: Forearm blood flow and acute release of tissue plasminogen activator. RESULTS: Mean arterial blood pressure fell during sildenafil infusion from a mean (SEM) of 92 (1) to 82 (1) mm Hg in patients and from 94 (1) to 82 (1) mm Hg in controls (p < 0.001 for both). Sildenafil increased endothelium independent vasodilatation with sodium nitroprusside (p < 0.05) but did not alter the blood flow response to acetylcholine or verapamil in patients or controls. Substance P caused a dose dependent increase in plasma tissue plasminogen activator antigen concentrations (p < 0.01) that was unaffected by sildenafil in either group. CONCLUSIONS: Sildenafil does not improve peripheral endothelium dependent vasomotor or fibrinolytic function in patients with coronary heart disease. Phosphodiesterase type 5 inhibitors are unlikely to reverse the generalised vascular dysfunction seen in patients with coronary heart disease.

3',5'-Cyclic-GMP Phosphodiesterases↗

PubMed1994

Endothelial nitric oxide and cardiovascular disease.

The vascular endothelium is the site of formation of several powerful mediators. One of these is NO, a chemically unstable radical formed by enzymatic conversion of L-arginine in the presence of molecular oxygen. NO elicits relaxation of VSMC by activating cytosolic guanylate cyclase. NO also counteracts platelet adhesion and aggregation. The biological actions of NO make it a key substance in the endogenous defense against vascular occlusion and thrombosis. The basal formation of NO maintains a moderate but significant vasodilation in the systemic resistance vessels and counteracts platelet activity. When blood flow in conduit arteries is increased there is an augmented endothelial formation of NO, eliciting flow-dependent vasodilation. Beside this, several vasodilators (acetylcholine, bradykinin, histamine, substance P) operate by stimulating endothelial NO formation. On the other hand, drugs like nitroglycerin and papaverine operate independently of the vascular endothelium. Vasodilator mechanisms, physiological as well as pharmacological, may therefore be characterized as endothelium-dependent (i.e. NO-mediated), or endothelium-independent (i.e. not mediated by NO). Physiologically, mixed mechanisms occur. Failure of the vascular endothelium to elicit NO-mediated vasodilatation may be due to decreased formation, increased degradation, decreased sensitivity to the NO formed, or a mixture of these factors. Irrespective of the mechanism behind, this is referred to as endothelial dysfunction. Endothelial dysfunction occurs in several cardiovascular settings, like atherosclerosis, hypercholesterolaemia, diabetes, and essential hypertension. Endothelial dysfunction leads to an impaired tissue perfusion, increased local vascular resistance, decreased defense against thrombus formation, and possibly also decreased defense against hypertrophy of the VSMC in the vessel wall media. In patients with CHD, endothelial dysfunction leads to an impaired coronary flow response to physical and mental stress, and to promotion of platelet adherence and aggregability. Endothelial dysfunction is thereby a probable aggravating factor in the atherosclerotic process, adding a functional component on top of the structural lesions characterizing this disease. A particular form of endothelial dysfunction, limited to the arterial resistance vessels, may explain the symptoms and clinical characteristics of microvascular angina. In patients with essential hypertension, endothelial dysfunction prevails, adding a functional component to the structural factors also in this disease. Hitherto, the only therapeutic tools available to restore endothelial dysfunction appear to be restriction of the dietary intake of lipids, possibly reinforced with intake of antioxidants like fish oil and vitamin E. However, large clinical trials to confirm the efficacy of such therapy in reversing endothelial dysfunction have not been conducted. In the future, more directly acting therapeutic regimens, aimed at supporting or substituting the endogenous formation of NO, are likely to appear as well.

Cardiovascular Diseases↗

PubMed2002

Coenzyme Q(10) improves endothelial dysfunction of the brachial artery in Type II diabetes mellitus.

AIM/HYPOTHESIS: We assessed whether dietary supplementation with coenzyme Q(10) improves endothelial function of the brachial artery in patients with Type II (non-insulin-dependent) diabetes mellitus and dyslipidaemia. METHODS: A total of 40 patients with Type II diabetes and dyslipidaemia were randomized to receive 200 mg of coenzyme Q(10) or placebo orally for 12 weeks. Endothelium-dependent and independent function of the brachial artery was measured as flow-mediated dilatation and glyceryl-trinitrate-mediated dilatation, respectively. A computerized system was used to quantitate vessel diameter changes before and after intervention. Arterial function was compared with 18 non-diabetic subjects. Oxidative stress was assessed by measuring plasma F(2)-isoprostane concentrations, and plasma antioxidant status by oxygen radical absorbance capacity. RESULTS: The diabetic patients had impaired flow-mediated dilation [3.8 % (SEM 0.5) vs 6.4 % (SEM 1.0), p = 0.016], but preserved glyceryl-trinitrate-mediated dilation, of the brachial artery compared with non-diabetic subjects. Flow-mediated dilation of the brachial artery increased by 1.6 % (SEM 0.3) with coenzyme Q(10) and decreased by -0.4 % (SEM 0.5) with placebo (p = 0.005); there were no group differences in the changes in pre-stimulatory arterial diameter, post-ischaemic hyperaemia or glyceryl-trinitrate-mediated dilation response. Coenzyme Q(10) treatment resulted in a threefold increase in plasma coenzyme Q(10) (p < 0.001) but did not alter plasma F(2)-isoprostanes, oxygen radical absorbance capacity, lipid concentrations, glycaemic control or blood pressure. CONCLUSION/INTERPRETATION: Coenzyme Q(10) supplementation improves endothelial function of conduit arteries of the peripheral circulation in dyslipidaemic patients with Type II diabetes. The mechanism could involve increased endothelial release and/or activity of nitric oxide due to improvement in vascular oxidative stress, an effect that might not be reflected by changes in plasma F(2)-isoprostane concentrations.

Antioxidants↗