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Results for “endothelial dysfunction”

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PubMed1993

[Endothelial dysfunction in ischemic syndromes].

Several studies have shown evidence of the key role of the endothelium in modulating the tone of epicardial coronary vessels, in the different manifestations of coronary artery disease. Recently, the role of endothelium-dependent vasodilation has been focused, because clinical observations have suggested that myocardial ischemia might be caused or aggravated by inappropriate vasoconstriction of resistance vessels. An abnormal endothelium-dependent vasodilation, either of epicardial and of coronary microvasculature, has been documented in patients with syndrome X and in patients with history of hypertension and left ventricular hypertrophy. Vasoconstriction of the small coronary vessels is probably the mechanism underlying the impaired increase of coronary blood flow during atrial pacing and the wide variations of the ischemic threshold in some patients with chronic stable angina. In patients with variant angina, the endothelial function seems abnormal only in the conductance vessels. It is likely that the endothelial dysfunction of the small coronary arteries be present in many clinical situations in which a discrepancy between a mild atherosclerosis of epicardial coronary artery and signs of ischemia exists, as it has been observed early after successful angioplasty and after coronary artery reperfusion during acute myocardial infarction.

Coronary Vessels↗

PubMed2005

Role of nitric oxide during coronary endothelial dysfunction after myocardial infarction.

This study aimed to investigate whether permanent ischaemia influences subacute vasodilatation responses of non-infarcted rat coronary vasculature, and to characterise these coronary changes. Ischaemia led to a significant impairment of the endothelium-dependent vasodilator response, while coronary vasodilatory capacity remained unaltered. In normal coronary circulation, nitric oxide (NO) and prostanoids contributed to vasodilatation, while basal involvement of endothelium-derived hyperpolarising factor was limited. Vasodilatory impairment following myocardial infarction did not originate from alterations in the prostanoid pathway, and only a slightly increased influence of K+ channels was observed. However, NO-mediated vasodilatation was significantly increased after ischaemia, as also confirmed by higher mRNA and protein levels of iNOS and eNOS. Additionally, the amount of superoxide was enhanced following infarction. We conclude that subacute postinfarction remodeling is accompanied by endothelial dysfunction in non-infarcted coronary arteries. Although the NO-mediated response is increased after ischaemia, its final action is restricted due to the presence of superoxide.

Adenosine↗

PubMed2005

Liver alanine aminotransferase, insulin resistance and endothelial dysfunction in normotriglyceridaemic subjects with type 2 diabetes mellitus.

BACKGROUND: Plasma levels of liver transaminases, including alanine aminotransferase (ALT), are elevated in most cases of nonalcoholic fatty liver disease (NAFLD). Elevated ALT levels are associated with insulin resistance, and subjects with NAFLD have features of the metabolic syndrome that confer high-risk cardiovascular disease. Alanine aminotransferase predicts the development of type 2 diabetes (DM2) in subjects with the metabolic syndrome. However, the role of elevated ALT levels in subjects with overt DM2 has yet not been explored. MATERIALS AND METHODS: In a cross-sectional study, 64 normotriglyceridaemic subjects with DM2 were studied with regard to the relation between liver transaminases with whole-body insulin sensitivity, measured with the euglycaemic hyperinsulinaemic clamp and with brachial artery flow-mediated dilation (FMD) as a marker of endothelial dysfunction. RESULTS: On average, patients were normotriglyceridaemic (plasma triglycerides 1.3 +/- 0.4 mmol L-1) and had good glycaemic control (HbA1c 6.2 +/- 0.8%). The mean ALT level was 15.0 +/- 7.5 U L-1, and the mean aspartate aminotransferase concentration equalled 10.6 +/- 2.6 U L-1. Alanine aminotransferase levels were negatively associated with whole-body insulin sensitivity as well as with FMD (both P = 0.03, in multivariate analyses; regression coefficients beta [95%CI]: -0.76 [-1.4 to -0.08] and -0.31 [-0.58 to -0.03] respectively). CONCLUSIONS: In metabolically well-controlled patients with DM2, ALT levels are related to decreased insulin-sensitivity and an impaired conduit vessel vascular function.

Adult↗

PubMed2002

Endothelial dysfunction in uterine circulation in preeclampsia: can estrogens improve it?

OBJECTIVE: The purpose of this study was to evaluate whether a 3-hour incubation with 17beta-estradiol will enhance blood flow- and bradykinin-mediated dilatation and alter pressure-induced basal tone in myometrial resistance arteries from women with preeclampsia and to evaluate the role of nitric oxide in the responses that were observed. STUDY DESIGN: Blood flow- and bradykinin-mediated dilatation and responses to intraluminal pressure of 60 and 80 mm Hg were compared before and after 3 hours of incubation with 17beta-estradiol (10(-8) mol/L) in isolated myometrial arteries with the pressure myography technique. In separate experiments, the role of nitric oxide on 17beta-estradiol-induced responses was evaluated in the presence of the nitric oxide synthase inhibitor (10(-4) mol/L). Endothelial morphologic condition was evaluated by scanning electron microscopy. RESULTS: Incubation with 17beta-estradiol significantly improved blood flow-mediated dilatation compared with initial blood flow-mediated response in arteries from women with preeclampsia. This effect was nitric oxide mediated, because the nitric oxide synthase inhibitor abolished the response. Arteries from women with preeclampsia demonstrated impaired bradykinin-mediated dilatation compared with that obtained in arteries from normal pregnant women. The 17beta-estradiol had no effect on bradykinin-mediated dilatation in arteries from women with preeclampsia. The enhanced pressure-induced tone at 80 mm Hg compared with the tone that developed at 60 mm Hg in arteries from women with preeclampsia was reduced after incubation with 17beta-estradiol. This reduction was also nitric oxide mediated. Morphologic signs of endothelial dysfunction were evident in arteries from women with preeclampsia. CONCLUSION: The 17beta-estradiol improved impaired blood flow-mediated dilatation and reduced basal tone through a nitric oxide-mediated pathway in isolated myometrial arteries from women with preeclampsia.

Adult↗

PubMed2005

[The role of oxidative metabolism disturbance in the development of NO-related endothelial dysfunction during chronic hearth failure].

The aim of the work was to establish the oxidative metabolism changes and NO data in Chronic Hearth Failure (HF). 52 patients were included in the investigation, among them 37 patients with CHD and chronic HF (II-IV functional class by NIHA) and 17 without it (control group). For revealing of organism redox-status (ceruloplasmine, Fe3+-transfferine, Mn2+, methemoglobine) the blood paramagnetic centers was studied by electron paramagnetic resonance method. For revealing of blood free NO, the diethyldithiocarbamat (SIGMA) was used. In chronic HF the oxidative process intensification and organism compensate reaction reduction with low Fe3+-transferine levels, increased Mn2++, methaemoglobin and inactivation of erythrocytes membranes adrenergic receptors were revealed. In chronic HF the accumulation of reactive oxygen levels provoke NO transformation in peroxynitrote with following decreases of blood free NO and develop the endothelial dysfunction.

Cardiac Output, Low↗

PubMed2006

Participation of reactive oxygen species in diabetes-induced endothelial dysfunction.

OBJECTIVES: In the present study, the relationship between diabetes-induced hyperglycemia, reactive oxygen species production and endothelium-mediated arterial function was examined. The effect of antioxidant on the reactive oxygen species induced damage was tested. METHODS: Diabetes was induced by streptozotocin (STZ), 3 x 30 mg/kg i.p., administered on three consecutive days. After 10 weeks of diabetes, the functional state of the endothelium of the aorta was tested, endothelemia evaluation was performed and systolic blood pressure was measured. Reactive oxygen species (ROS) formation in blood and the aorta was measured using luminol-enhanced chemiluminescence (CL). Levels of reduced glutathione (GSH) were determined in the aorta, kidney, and plasma. To study the involvement of hyperglycemia in functional impairment of the endothelium, aortal rings incubated in solution with high glucose concentration were tested in in vitro experiments. RESULTS: After 10 weeks of diabetes, endothelial injury was observed, exhibited by diminished endothelium-dependent relaxation of the aorta, increased endothelemia and by elevated systolic blood pressure. Using luminol-enhanced CL, a significant increase of ROS production was found in arterial tissue and blood. GSH levels were significantly increased in the kidney, while there were no GSH changes in plasma and the aorta. Incubation of aortic rings in solution with high glucose concentration led to impairment of endothelium-dependent relaxation. The synthetic antioxidant SMe1EC2 was able to restore reduced endothelium-mediated relaxation. CONCLUSIONS: Our results suggest an important role of hyperglycemia-induced ROS production in mediating endothelial dysfunction in experimental diabetes, confirmed by CL and the protective effect of the antioxidant SMe1EC2.

Acetylcholine↗

PubMed1998

Arterial injury by cholesterol oxidation products causes endothelial dysfunction and arterial wall cholesterol accumulation.

Cholesterol oxidation products (ChOx) have been reported to cause acute vascular injury in vivo; however, the pharmacokinetics of ChOx after administration and the mechanisms by which they cause chronic vascular injury are not well understood. To further study the pharmacokinetics and atherogenic properties of ChOx, New Zealand White rabbits were injected intravenously (70 mg per injection, 20 injections per animal) with a ChOx mixture having a composition similar to that found in vivo during a 70-day period. Total ChOx concentrations in plasma peaked almost immediately after a single injection, declined rapidly, and returned to preinjection levels in 2 hours. After multiple injections, the ChOx concentrations rose gradually to levels 2- to 3-fold above baseline levels, increasing mostly in the cholesteryl ester fraction of LDL and VLDL. Rabbit serum and the isolated LDL/VLDL fraction containing elevated ChOx concentrations were cytotoxic to V79 fibroblasts and rabbit aortic endothelial cells. At the time of killing, cholesterol levels in the aortas from ChOx-injected rabbits were significantly elevated despite the fact that plasma cholesterol levels remained in the normal range. In addition, aortas from the ChOx-injected rabbits retained more 125I-labeled horseradish peroxidase, measured 20 minutes after intravenous injection. Transmural concentration profiles across the arterial wall also showed increased horseradish peroxidase accumulation in the inner half of the media from the thoracic aorta in ChOx-injected rabbits. In conclusion, ChOx injection resulted in accumulation of circulating ChOx and induced increased vascular permeability and accumulation of lipids and macromolecules. This study reveals that even under normocholesterolemic conditions, ChOx can cause endothelial dysfunction, increased macromolecular permeability, and increased cholesterol accumulation, parameters believed to be involved in the development of early atherosclerotic lesions.

Animals↗

PubMed2004

Endothelial dysfunction as a modifier of angiogenic response in Zucker diabetic fat rat: amelioration with Ebselen.

BACKGROUND: Progression of nephropathy in metabolic syndrome is associated with microvasculopathy and vascular dropout. METHODS: Eight- and 22-week-old Zucker diabetic fat (ZDF) and Zucker lean (ZL) rats were studied to characterize the progression of nephropathy, and to test the effect of a peroxynitrite scavenger, Ebselen, on renal microvasculature and angiogenic competence. RESULTS: Capillary density was increased, both in the cortex (P < 0.05) and in the inner medulla (P < 0.001) by the age of 8 weeks, but significantly decreased (P < 0.01 and P < 0.001) by the age of 22 weeks in ZDF compared to ZL rats. Similarly, the angiogenic competence of cortical and medullary renal explants was increased in 8-week-old ZDF (P < 0.01), but decreased at 22 weeks (P < 0.001). Alterations of angiogenic competence in ZDF rats were associated with altered expression of vascular endothelial growth factor (VEGF), reduced expression of Flk-1, and neuropilin. Acetylcholine-induced relaxation of microdissected interlobar arteries from 8-week-old ZDF rats was unimpaired, but significantly attenuated in 22-week-old ZDF rats (P < 0.001). Treatment with Ebselen partially prevented the decrease in capillary density and angiogenic competence of renal explants, and restored acetylcholine-induced vasorelaxation in 22-week-old ZDF rats. CONCLUSION: The progression of nephropathy in ZDF rats is associated with decreased angiogenic competence both ex vivo and in vivo. This is accompanied by a altered expression of VEGF system components and endothelial dysfunction, and scavenging peroxynitrite with Ebselen ameliorates the progression of microvasculopathy and partially restores angiogenesis. These findings reveal the complex mechanism of microvascular dropout in experimental metabolic syndrome.

Acetylcholine↗

PubMed2001

Endothelial dysfunction in patients with polycythaemia vera.

Patients with polycythaemia vera (PV) are at increased risk of developing arterial and venous thromboembolic complications. We investigated whether endothelium-dependent, flow-mediated vasodilatation (FMD) is impaired in PV patients without clinical evidence of artery disease as observed in patients with conventional cardiovascular risk factors. FMD and endothelium-independent, nitroglycerine-induced vasodilatation (NMD) were assessed using high-resolution ultrasound in the brachial artery of 20 patients with PV and 20 sex- and age-matched control subjects (CTL). FMD was markedly impaired in PV patients compared with CTL (7.6 +/- 2.9% versus 11.6 +/- 5.7%, P = 0.009) whereas NMD was similar in both study groups. The impairment of FMD was independently related to the presence of PV (r = -0.434, P = 0.009) and vessel size (r = -0.107, P = 0.038) but was not related to haematocrit values and platelet counts. The results demonstrate that PV is associated with endothelial dysfunction in the pre-clinical phase of arterial disease. However, the precise mechanisms by which PV leads to this altered vascular reactivity remain unclear.

Adult↗

PubMed2006

Vascular NAD(P)H oxidase mediates endothelial dysfunction in basilar arteries from Otsuka Long-Evans Tokushima Fatty (OLETF) rats.

We examined the responses of basilar arteries taken from Otsuka Long-Evans Tokushima Fatty (OLETF) rats, a type 2 diabetes model. Both the nitric oxide (NO)-mediated relaxation and the cyclic 3',5'-guanosine monophosphate (cGMP) production elicited by acetylcholine (ACh) were much weaker in OLETF rats than in age-matched control Long Evans Tokushima Otsuka (LETO) rats. The contraction induced by an NO synthase (NOS) inhibitor [N(G)-nitro-L-arginine (L-NNA)] was weaker in the OLETF group. In that group, application of apocynin, an NAD(P)H oxidase inhibitor, normalized (i) ACh-induced relaxation, (ii) L-NNA-induced contraction, and (iii) ACh-induced cGMP production to the LETO levels. Superoxide anion production was greater in basilar arteries from OLETF rats than in those from LETO rats. The protein expression of gp91(phox), an NAD(P)H oxidase subunit, was upregulated in the OLETF arteries (versus LETO ones). These results suggest that the existence of endothelial dysfunction in basilar arteries in type 2 diabetes is related to increased oxidative stress mediated via NAD(P)H oxidase. Possibly, an impairment of NO-dependent relaxation responses and a basal impairment of NO signaling may be responsible for the increased risk of adverse cerebrovascular events in type 2 diabetes.

Acetophenones↗

PubMed1998

Endothelial dysfunction in human intramyocardial small arteries in atherosclerosis and hypercholesterolemia.

Vascular responses of human intramyocardial small arteries were examined in vitro to assess the influence of atherosclerosis and risk factors for coronary artery disease on endothelium-dependent relaxation. Recipient hearts were obtained from patients with ischemic (n = 14) and nonischemic (n = 13) cardiomyopathy undergoing heart transplantation. Small intramyocardial coronary arteries (mean internal diameter 313 +/- 11 micrometers) were mounted on a wire myograph for measurement of morphology and isometric tension. Vasodilation was examined after preconstriction with U-46619, a thromboxane A2 analog. Endothelium-dependent relaxation to acetylcholine and bradykinin was impaired in patients with ischemic compared with nonischemic cardiomyopathy (P < 0.01 and P < 0.001, respectively). Endothelium-independent relaxation to sodium nitroprusside was preserved. Incubation with L-arginine (3 mmol/l) did not improve endothelium-dependent relaxation to acetylcholine or bradykinin. With the use of stepwise multivariate analysis, hypercholesterolemia, but no other risk factor for atherosclerosis, was independently associated with impaired endothelium-dependent relaxation to acetylcholine (r = -0.50, P = 0.05) but not to bradykinin. Endothelial dysfunction in intramyocardial small arteries may predispose patients with nonobstructive epicardial atherosclerosis and hypercholesterolemia to myocardial ischemia.

15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5↗

PubMed2005

Mechanisms of endothelial dysfunction with development of type 1 diabetes mellitus: role of insulin and C-peptide.

Complications associated with insulin-dependent diabetes mellitus (type-1diabetes) primarily represent vascular dysfunction that has its origin in the endothelium. While many of the vascular changes are more accountable in the late stages of type-1diabetes, changes that occur in the early or initial functional stages of this disease may precipitate these later complications. The early stages of type-1diabetes are characterized by a diminished production of both insulin and C-peptide with a significant hyperglycemia. During the last decade numerous speculations and theories have been developed to try to explain the mechanisms responsible for the selective changes in vascular reactivity and/or tone and the vascular permeability changes that characterize the development of type-1diabetes. Much of this research has suggested that hyperglycemia and/or the lack of insulin may mediate the observed functional changes in both endothelial cells and vascular smooth muscle. Recent studies suggest several possible mechanisms that might be involved in the observed decreases in vascular nitric oxide (NO) availability with the development of type-1 diabetes. In addition more recent studies have indicated a direct role for both endogenous insulin and C-peptide in the amelioration of the observed endothelial dysfunction. These results suggest a synergistic action between insulin and C-peptide that facilitates increase NO availability and may suggest new clinical treatment modalities for type-1 diabetes mellitus.

C-Peptide↗

PubMed1992

Heterogeneity of endothelial dysfunction in hypertension.

The endothelium may play a role as a target and mediator of hypertension. Due to its anatomical position, it is very exposed to mechanical forces; as a source of vasoactive material it may participate in increasing peripheral vascular resistance and in promoting local ischaemia in the heart and brain. Morphological and functional changes in the endothelium occur in experimental and human hypertension. However, the severity of the defect and the mechanisms involved among vascular beds and models of hypertension are heterogeneous. Endothelium-dependent relaxations are impaired in the aorta, carotid artery and in cerebral and mesenteric arterioles in hypertension. In the coronary circulation the defect is less pronounced. The mechanisms involve a reduced formation of nitric oxide, an enhanced production of prostaglandin H2 and an impaired responsiveness of vascular smooth muscle to nitric oxide. The role of endothelin in hypertension is controversial; circulating levels appear unaltered except in the presence of renal failure or atherosclerosis. The local vascular production of endothelin, however, may still be increased. The potentiating effects of threshold concentrations of endothelin on the vasoconstrictor response to noradrenaline are enhanced in hypertension. Thus, subtle and distinct endothelial function defects occur in hypertension, but not all vascular beds are similarly affected and different mechanisms contribute. Endothelial dysfunction may contribute to increased peripheral resistance, tissue ischaemia and cardiovascular complications.

Animals↗

PubMed2000

Fluvastatin suppresses atherosclerotic progression, mediated through its inhibitory effect on endothelial dysfunction, lipid peroxidation, and macrophage deposition.

Fluvastatin, a potent 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitor, exerts an inhibitory effect on intimal thickening after mechanical injury in normocholesterolemic rabbit artery at a dose not enough to elicit a known action of lipid lowering. This study was designed to determine whether atherosclerotic progression triggered by hypercholesterolemia can be inhibited by fluvastatin under conditions without its hypocholesterolemic effect. Rabbits were fed a 0.5% cholesterol diet or normal diet for 17 weeks and were treated with either fluvastatin (0.3-2 mg/kg/day, p.o.) or pravastatin (2 mg/kg/day, p.o.). Atherogenic features manifested in the cholesterol-diet group, compared with the normal-diet group; they were the increase in serum lipid peroxide level, in the intraluminal lesion area of the aorta, and in macrophage content of the aortic cross-sectional lesion area; the attenuation of endothelium-dependent relaxing response to acetylcholine in the femoral artery; and the increase in serum lipid level. Treatment with fluvastatin, but not pravastatin, inhibited the manifestation of the atherogenic features without a serum lipid-lowering effect. Thus fluvastatin is likely to reduce the risk of atherosclerotic progression, to which endothelial dysfunction, lipid peroxidation, and macrophage accumulation in the vasculature may contribute, irrespective of changes in serum lipid levels.

Animals↗

PubMed2003

Interactions between inflammation, oxidative stress, and endothelial dysfunction in end-stage renal disease.

Despite a rapid improvement in dialysis technology during the last 20 years, the mortality rate is still very high in patients with end-stage renal disease (ESRD), and the death rate is comparable with that of many cancer patients with metastases. The main cause of mortality in ESRD is cardiovascular disease (CVD), and cardiac mortality for dialysis patients aged 45 years or younger is more than 100-fold greater than in the general population. The high cardiovascular mortality rate suggests that ESRD patients are subjected to a process of accelerated atherogenesis. Because factors proven to contribute to atherosclerosis in the general population, such as dyslipidemia, smoking, diabetes mellitus, and hypertension are highly prevalent in ESRD patients, it is reasonable to assume that such risk factors also apply to these patients. However, as it has been shown that the high cardiovascular risk in ESRD is incompletely accounted for by traditional risk factors, it may be speculated that nontraditional risk factors, seemingly more difficult to reconcile, also contribute. Among several putative nontraditional risk factors, chronic inflammation has attracted a lot of interest recently because it seems to be associated to both increased vascular oxidative stress and endothelial dysfunction, both of which are important predictors of cardiovascular events in nonrenal patient groups.

Anti-Inflammatory Agents↗

PubMed2003

CB(1) cannabinoid receptor antagonism promotes remodeling and cannabinoid treatment prevents endothelial dysfunction and hypotension in rats with myocardial infarction.

1. To study the long-term effects of altered cannabinoid receptor activity on myocardial and vascular function, Wistar rats were treated with the selective CB(1) antagonist AM-251 (0.5 mg kg(-1) d(-1)), the potent synthetic cannabinoid HU-210 (50 micro g kg(-1) d(-1)) or vehicle for 12 weeks after coronary artery ligation or sham operation. 2. AM-251 further reduced the pressure-generating capacity, shifted the pressure volume curve to the right (P<0.05) and increased the left-ventricular operating volume (AM-251: 930+/-40 micro l vs control: 820+/-40 micro l vs HU-210: 790+/-50 micro l; P<0.05) in rats with large myocardial infarction (MI). 3. Left-ventricular CB(1) immunoactivity in rats 12 weeks after large MI was unaltered as compared with noninfarcted hearts. 4. Cannabinoid receptor activation through HU-210, a cannabinoid that alters cardiovascular parameters via CB(1) receptors, increased the left-ventricular end-diastolic pressure (LVEDP, P<0.05). However, it prevented the drop in left-ventricular systolic pressure (HU-210: 142+/-5 mm Hg; P<0.05 vs control: 124+/-3 mm Hg; and P<0.001 vs AM-251: 114+/-3 mm Hg) and prevented endothelial dysfunction (ED) in aortic rings of rats with large MI (P<0.05). 5. Compared with AM-251, HU-210 prevented the decline in the maximal rate of rise of left-ventricular pressure and the maximum pressure-generating ability (P<0.05). In rats with small MI, HU-210 increased cardiac index (P<0.01) and lowered the total peripheral resistance (P<0.05). 6. The study shows that during the development of congestive heart failure post-large MI, cannabinoid treatment increases LVEDP and prevents hypotension and ED. Presumed CB(1) antagonism promotes remodeling despite unchanged myocardial CB(1) expression.

Animals↗

PubMed2003

Interleukin-6 induces oxidative stress and endothelial dysfunction by overexpression of the angiotensin II type 1 receptor.

Angiotensin II type 1 (AT1) receptor activation as well as proinflammatory cytokines such as interleukin-6 (IL-6) are involved in the development and progression of atherosclerosis. The detailed underlying mechanisms including interactions between inflammatory agonists and the renin-angiotensin system are poorly understood. Stimulation of cultured rat aortic vascular smooth muscle cells (VSMCs) with IL-6 led to upregulation of AT1 receptor mRNA and protein expression, as assessed by Northern and Western blot experiments. Nuclear run-on and transcription blockade experiments showed that IL-6 increases AT1 receptor mRNA de novo synthesis but not mRNA stability. Preincubation of VSMCs with IL-6 resulted in an enhanced angiotensin II-induced production of reactive oxygen species, as assessed by DCF fluorescence laser microscopy. Treatment of C57BL/6J mice with IL-6 for 18 days increased vascular AT1 receptor expression (real-time RT-PCR) and angiotensin II-induced vasoconstriction, enhanced vascular superoxide production (L-012 chemiluminescence, DHE fluorescence), and impaired endothelium-dependent vasodilatation. These effects were completely omitted in AT1 receptor knockout mice (AT1A-/- mice). Upregulation of vascular AT1 receptor expression in vitro and in vivo is decisively involved in IL-6-induced propagation of oxidative stress and endothelial dysfunction. This interaction of the proinflammatory cytokine IL-6 with the renin-angiotensin system may represent an important pathogenetic mechanism in the atherosclerotic process.

Animals↗

PubMed2004

Glucose levels observed in daily clinical practice induce endothelial dysfunction in the rabbit macro- and microcirculation.

We investigated whether different concentrations of elevated glucose - corresponding to levels observed in patients with type 2 diabetes under routine care (post-prandial mean and maximum values) and those used for diagnosing diabetes - induce impairment of vascular reactivity of the macro- and microcirculation in non-diabetic rabbits. Aortic rings and isolated perfused kidneys from normal rabbits were acutely exposed (3 h) to normal (5.5 mm) or high (7-25 mM) D-glucose concentrations. Vascular reactivity was evaluated with endothelium-dependent [acetylcholine (ACh) and bradykinin (BK)] and independent [sodium nitroprusside (SNP)] vasodilating agents. Endothelium-dependent relaxation of the thoracic aorta induced by ACh or BK was significantly attenuated after a 3-h exposure to high D-glucose (15-25 mM) but not after corresponding increased osmolarity with mannitol solutions. Relaxation induced by SNP (endothelium-independent) was not affected by high D-glucose concentrations. Moreover, endothelium-dependent but not independent vasodilation of the isolated rabbit kidney was also impaired after 3-h perfusion with high D-glucose (11.1-25 mM). Perfusion with mannitol solutions (15-25 mM) partially blunted endothelium-dependent renal vasodilation. It is concluded that acute hyperglycemia corresponding to post-prandial levels in patients with type 2 diabetes induces endothelial dysfunction of conduit vessels as well as of the renal circulation of non-diabetic rabbits.

Animals↗