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Results for “endothelial dysfunction”

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PubMed2003

Diffuse endothelial dysfunction is common to ANCA associated systemic vasculitis and polyarteritis nodosa.

BACKGROUND: Excess cardiovascular mortality complicates systemic rheumatic disease, suggesting an accelerated atheromatous process, which it has been proposed relates to the vascular inflammation common in such diseases. Impaired endothelium dependent vasodilatation is an early marker of atheromatous disease. It has previously been shown that such endothelial cell dysfunction (ECD) occurring in the brachial artery can complicate primary systemic necrotising vasculitis (SNV). OBJECTIVE: To determine if ECD occurs in a wider spectrum of primary SNV, if it is restricted to the major arteries, and whether vasculitis subgroup, ANCA status, or renal involvement influenced the endothelial responses. METHODS: Fifty four patients attending the Birmingham vasculitis clinic, including patients with a range of ANCA and non-ANCA associated primary vasculitides, and a group of age matched controls were recruited. The length of patient follow up and disease activity was variable. Disease activity, damage scores, and cardiovascular risk factors were recorded before assessment of flow mediated brachial artery vasodilatation by high resolution ultrasound. Dermal microvascular responses to acetylcholine were also measured in 32 patients and 21 controls by laser Doppler flowmetry. RESULTS: ECD was demonstrated in all primary SNV subgroups of patients with ANCA associated vasculitis and in polyarteritis nodosa, compared with controls. Significant impairment occurred in both vascular beds, regardless of vessel size targeted in the inflammatory vasculitis, ANCA association and titre, or renal involvement. CONCLUSIONS: Diffuse endothelial dysfunction, a predictor of atherosclerotic disease, is found extensively in primary systemic vasculitis. Involvement of different vascular beds is independent of target vessel size or ANCA association, and is unrelated to local disease expression. It is suggested that this results from a systemic response that may be a consequence of primary vasculitis, but is distinct from the local inflammatory vasculitic process.

Adult↗

PubMedDate not supplied

Correlation between soluble markers of endothelial dysfunction in patients with renal failure.

AIM: Damage to the endothelium is an important component of atherosclerosis. It has been suggested to be quantified by measuring plasma markers, such as von Willebrand factor and thrombomodulin and soluble adhesion molecules. We hypothesized there may exist a correlation between the plasma levels of von Willebrand factor and thrombomodulin as markers of endothelial cell dysfunction and the serum concentrations of soluble adhesion molecules and monocyte chemoattractant protein-1 (MCP-1) in patients with renal insufficiency, and in patients on peritoneal dialysis or hemodialysis since these three groups of kidney patients are highly prone to develop cardiovascular diseases. RESULTS: The concentrations of von Willebrand factor and thrombomodulin in plasma were significantly higher in patients with kidney diseases as compared to healthy subjects (p = 0.017 and p < 0.001, respectively). The patients also had significantly higher concentrations of soluble vascular cell adhesion molecule-1 (sVCAM-1) and MCP-1 compared to healthy controls (p < 0.001 for both comparisons). There were strong correlations between the concentration of soluble intercellular adhesion molecule-1 (sICAM-1) and von Willebrand factor in patients with kidney failure (r = 0.63, p < 0.001) and between the concentration of thrombomodulin and sVCAM-1 (r = 0.61, p < 0.001). Furthermore, a negative correlation was observed between the concentration of thrombomodulin and the cell surface expression of CD11b on monocytes and granulocytes in the peripheral circulation (p < 0.01 in both cases). CONCLUSION: The strong correlation between markers of endothelial dysfunction and soluble adhesion molecules in patients with renal insufficiency and on dialysis strengthen the view that an ongoing stress on endothelial cells is present in this group of patients. This may play a pathophysiological role in the development of cardiovascular disease.

Aged↗

PubMed2005

Endothelial dysfunction occurs in peripheral circulation patients with acute and stable coronary artery disease.

Atherosclerosis is a diffuse, systemic process. In addition, acute coronary syndromes (ACS) are associated with inflammatory marker elevations that are hypothesized to affect the function of nonculprit coronary as well as peripheral vessels. We investigated whether femoral vascular reactivity and/or fibrinolytic capacity are impaired in ACS patients over and above any dysfunction associated with stable coronary artery disease. Patients undergoing diagnostic coronary angiography (n = 42 total, 14 patients/group) were recruited into three groups as follows: 1) stable coronary syndromes (SAP group), 2) ACS as defined by rest angina with ECG changes and troponin rise (ACS group), and 3) angiographically normal coronary arteries (control group). After diagnostic coronary angiography, femoral artery endothelial and smooth muscle function were assessed by infusing acetylcholine (ACh) and nitroglycerin (GTN), and tissue-type plasminogen activator (t-PA) release across the femoral circulation was measured as the difference between arterial and venous concentrations before and after ACh and GTN stimulation. There were no significant differences between groups in relevant baseline characteristics apart from significantly higher C-reactive protein levels and reduced net t-PA release in the ACS group at baseline (P < 0.05). The ACS and SAP groups had equivalent angiographic severity of coronary artery disease. Endothelium-dependent dilatation was significantly higher in control individuals (14.9 +/- 9.1%; P < 0.001) compared with either stable patients (2.3 +/- 8.1%) or those with unstable syndromes (2.6 +/- 8.9%, who were similar to each other; P = not significant). Although baseline t-PA release was impaired in the ACS patients (0.09 +/- 0.06 compared with 0.39 +/- 0.33 and 0.49 +/- 0.56 ng/ml; P = 0.03), stimulation of t-PA release by ACh and GTN occurred only in the control subjects and not in the ACS or SAP patients. Coronary artery disease is associated with impaired endothelium-dependent dilatation and impaired stimulation of t-PA release in the systemic circulation. These aspects of endothelial dysfunction, however, were equally severe in acute and chronic coronary syndrome patients.

Acetylcholine↗

PubMed2000

Endothelial dysfunction in cardiovascular diseases: the role of oxidant stress.

Accumulating evidence suggests that oxidant stress alters many functions of the endothelium, including modulation of vasomotor tone. Inactivation of nitric oxide (NO(.)) by superoxide and other reactive oxygen species (ROS) seems to occur in conditions such as hypertension, hypercholesterolemia, diabetes, and cigarette smoking. Loss of NO(.) associated with these traditional risk factors may in part explain why they predispose to atherosclerosis. Among many enzymatic systems that are capable of producing ROS, xanthine oxidase, NADH/NADPH oxidase, and uncoupled endothelial nitric oxide synthase have been extensively studied in vascular cells. As the role of these various enzyme sources of ROS become clear, it will perhaps be possible to use more specific therapies to prevent their production and ultimately correct endothelial dysfunction.

Animals↗

PubMed2004

The neuroprotective effect of the antioxidant flavonoid derivate di-tert-butylhydroxyphenyl is parallel to the preventive effect on post-ischemic Kir2.x impairment but not to post-ischemic endothelial dysfunction.

In the rat model of transient cerebral ischemia induced by intraluminal occlusion of the middle cerebral artery, we investigated the respective roles of ischemia and reperfusion in endothelium-dependent relaxation and smooth muscle relaxation related to the inward rectifier potassium current (Kir2.x), using the Halpern arteriography technique and/or patch-clamp technique. We first demonstrated that reperfusion is necessary to induce a significant impairment of smooth muscle Kir2.x, since ischemia alone has no effect on Kir2.x current density and function. In addition, we demonstrated that both ischemia and reperfusion are necessary for the occurrence of maximal post-ischemic endothelial dysfunction. The crucial role of reperfusion in post-ischemic vascular impairment prompted us to characterize the effect of a new antioxidant synthetic flavonoid derivate, 3'5'di- tert-butylhydroxyphenyl (dt-BC), on both neuronal and vascular injuries. Dt-BC (10 mg/kg) induced a neuroprotective effect as demonstrated by a significant decrease in infarct size, while there was no protective effect with the doses of 3 mg/kg and 30 mg/kg. Parallel to neuroprotection, dt-BC at a dose of 10 mg/kg, but not with doses of 3 mg/kg and 30 mg/kg, prevented post-ischemic impairment of smooth muscle Kir2.x current density and function, while dt-BC had no effect on the post-ischemic alteration of endothelial function whatever doses are used. These data demonstrate the potential of a new synthetic flavonoid derivate to induce neurovascular protection and support a possible relationship between vascular and neuronal protection via pharmacological modulation of oxidative stress.

Animals↗

PubMed2004

Predictive adaptive responses to maternal high-fat diet prevent endothelial dysfunction but not hypertension in adult rat offspring.

BACKGROUND: Population-based studies suggest that fetal adaptive responses to maternal dietary imbalance confer survival benefit when the postnatal diet remains suboptimal but increase susceptibility to cardiovascular disease when postnatal nutrition is improved. We have investigated "predictive adaptive" responses in a rodent model in which adult offspring of fat-fed dams develop characteristics of the metabolic syndrome. METHODS AND RESULTS: Sprague-Dawley rats were fed a fat-rich diet or normal chow throughout pregnancy and weaning. Vascular endothelial function and blood pressure were determined in 180-day-old offspring of fat-fed dams raised on standard chow (FC) or on the fat-rich diet (FF) and in offspring of chow-fed dams raised on chow (CON). Small mesenteric artery endothelium-dependent dilation to acetylcholine was impaired in male and female FC (by ANOVA, P<0.001 versus CON) but similar to CON in FF (P=NS). Blood glucose was lower in FF versus FC. Heart rate was reduced in male FC versus CON (P<0.05) but not in FF. Plasma triglyceride concentrations were reduced in male FF compared with CON (P<0.05). Blood pressure was raised in female FC (systolic, 132.5+/-3.0 mm Hg versus CON, 119.0+/-3.8 mm Hg, P<0.05; diastolic, 91.2+/-1.7 mm Hg versus CON, 81.1+/-1.4 mm Hg, P<0.05) and in female FF (systolic, 132.5+/-4.2 mm Hg versus CON, P<0.05; diastolic, 91.0+/-1.9 mm Hg versus CON, P<0.05). Blood pressure was similar to CON in male FC and FF. CONCLUSIONS: Predictive adaptive responses prevent endothelial dysfunction and reduced heart rate in offspring of fat-fed dams if offspring are raised on the same diet but do not prevent development of raised blood pressure.

Adaptation, Physiological↗

PubMed2005

A lethal tetrad in diabetes: hyperglycemia, dyslipidemia, oxidative stress, and endothelial dysfunction.

This paper addresses the consequences of diabetes and obesity, diseases that have become epidemic in our society, particularly in the past 20 years. Specifically, it summarizes current knowledge about some of the risk factors and mechanisms for the vascular complications of diabetes. These complications can be broadly divided into microvascular disease, such as diabetic retinopathy and diabetic nephropathy, and macrovascular disease, such as accelerated atherosclerosis, and they are the main cause for morbidity and premature mortality among diabetic patients. The roles of hyperglycemia, dyslipidemia and dyslipoproteinemia, oxidative stress, and endothelial dysfunction will be considered. Finally, the "treatment gap" will be addressed. This gap refers to our failure to achieve currently accepted goals to reduce established risk factors for complications in the clinical management of diabetic patients.

Diabetes Mellitus↗

PubMed1992

Patients with evidence of coronary endothelial dysfunction as assessed by acetylcholine infusion demonstrate marked increase in sensitivity to constrictor effects of catecholamines.

BACKGROUND: Studies in patients undergoing cardiac catheterization have demonstrated that normal coronary arteries dilate and atherosclerotic arteries constrict in response to exercise and the cold pressor test, but the mechanisms are unknown. These vasomotor responses are mirrored by the vasomotor response to the endothelium-dependent agent acetylcholine. Exercise and the cold pressor test are associated with adrenergic stimulation and increased circulating catecholamines. The present study tested the hypothesis that coronary arteries with intact endothelial function are relatively resistant to the constrictor effects of catecholamines, whereas arteries with loss of endothelial function have increased sensitivity to catecholamine-induced constriction. METHODS AND RESULTS: The vasomotor function of the coronary endothelium was assessed by serial acetylcholine infusions (final concentration, 10(-8) to 10(-6) M) in 30 segments in 15 patients with minimal or no evidence of coronary atherosclerosis. The acetylcholine responses were related to the vasomotor response to intracoronary phenylephrine infusion (final concentration, 10(-9) to 10(-6) M) in the same segments. In the group of 18 segments that constricted to acetylcholine, there was a constrictor response to phenylephrine at an approximately 100-fold lower concentration than the group of 12 segments that did not constrict to acetylcholine. CONCLUSIONS: These results suggest that the endothelial dysfunction that characterizes early and late atherosclerosis is associated with a marked increase in sensitivity to the constrictor effects of catecholamines. This finding may explain the constrictor responses of atherosclerotic coronary arteries to exercise and the cold pressor test. In stenotic coronary arteries this mechanism may play a role in the production of myocardial ischemia.

Acetylcholine↗

PubMed1998

Long-term endothelial dysfunction is more pronounced after stenting than after balloon angioplasty in porcine coronary arteries.

OBJECTIVE: To compare percutaneous transluminal coronary angioplasty (PTCA) and stent implantation with respect to the long-term changes they induce in the newly formed endothelium in porcine coronary arteries by studying both morphological and functional parameters of the endothelium at 2 weeks and 3 months after intervention. BACKGROUND: Problems affecting PTCA or stent implantation have been overcome to a large extent by means of better techniques and the availability of new drugs. Late problems, however, still exist in that restenosis affects a large number of patients. With an increasing number of patients being treated with stents, the problem of in-stent restenosis is of even greater concern, as this seems difficult to treat. A functional endothelial lining is thought to be important in controlling the growth of the underlying vascular tissue. We hypothesized that the enhanced neointimal hyperplasia observed after stenting is associated with a more pronounced and prolonged endothelial dysfunction. METHODS: Arteries were analyzed using a dye-exclusion test and planimetry of permeable areas. Thereafter, the arteries were processed for light and scanning electron microscopy for assessment of morphology and proliferative response. RESULTS: Leakage of the endothelium for molecules such as Evans blue-albumin as well as prolonged endothelial proliferation is observed as late as 3 months after the intervention, and is more pronounced after stenting. Permeability is associated with distinct morphologic characteristics: endothelial retraction, the expression of surface folds, and the adhesion of leukocytes. CONCLUSIONS: Stenting especially decreases long-term vascular integrity with respect to permeability and endothelial proliferation, and is associated with distinct morphologic characteristics.

Angioplasty, Balloon, Coronary↗

PubMed2001

Endothelial dysfunction in salt-sensitive essential hypertension.

The aim of this study was to evaluate endothelium-dependent and -independent vasodilation, as well as endothelium biochemical markers, in a group of essential hypertensive patients classified on the basis of salt sensitivity. Changes in forearm blood flow in response to acetylcholine, sodium nitroprusside, and N(G)-monomethyl-L-arginine (L-NMMA) infusion were determined by means of strain-gauge plethysmography. Moreover, plasma and urinary concentrations of nitrates, cGMP, and endothelin were measured during low (50 mmol/d) and high (250 mmol/d) salt intake. Salt-sensitive hypertension was diagnosed in 26 patients who exhibited a significant increase in 24-hour mean blood pressure assessed by ambulatory blood pressure monitoring after 1 week of high salt intake. Nineteen patients were considered salt resistant. Compared with salt-resistant hypertensives, salt-sensitive patients presented a significant lower (P=0.005) maximal acetylcholine-induced vasodilation (21+/-6.3 versus 28+/-7.5 mL. 100 mL(-1). tissue. min(-1)). On the contrary, maximal sodium nitroprusside-induced vasodilation did not significantly differ between groups (22.4+/-4.5 versus 23.9+/-5.3 mL. 100 mL(-1). tissue. min(-1)). The decrease in maximal acetylcholine-induced vasodilation promoted by the coadministration of L-NMMA was significantly more pronounced in salt-resistant compared with salt-sensitive patients (P=0.003). Finally, high salt intake promoted a significant decrease in 24-hour urinary nitrate excretion in salt-sensitive patients (from 443+/-54 to 312+/-54 micromol/d; P=0.033) compared with salt-resistant hypertensives (from 341+/-50 to 378+/-54 micromol/d). We conclude that salt-sensitive hypertension is associated with endothelial dysfunction characterized by a defective endothelium-dependent vasodilation. Impairment of the L-arginine-nitric oxide pathway may be responsible for this abnormal endothelial response.

Acetylcholine↗

PubMedDate not supplied

Role of endothelium-derived hyperpolarizing factor in endothelial dysfunction during diabetes.

1. Under normal conditions, the endothelium plays a major role in the maintenance of vasodilatory tone via the production of endothelium-derived vasodilator agents, such as prostacyclin, nitric oxide and endothelium-derived hyperpolarizing factor (EDHF). Inhibition of endothelium-dependent relaxation features prominently in a range of cardiovascular diseases, including hypertension, coronary artery disease and diabetes. 2. Endothelium-derived hyperpolarizing factor is a prominent vasodilator, particularly in smaller arteries and arterioles. There is now emerging evidence to suggest that EDHF may play a role in the endothelial dysfunction in diabetes. 3. Since the first description of endothelium-dependent hyperpolarization some 20 years ago, it has emerged that EDHF is heterogeneous in nature, consisting of diffusible factors and contact-mediated mechanisms. The specific identity of EDHF in any particular vascular bed may influence the impact of diabetes on vascular function. 4. There is accumulating evidence in diabetic rat models and humans showing impaired EDHF activity in small resistance vessels. In contrast, studies in mice suggest that EDHF activity is actually enhanced under diabetic conditions. 5. It is clear that alterations in EDHF activity may have an important contribution in diabetes, more specifically in contributing to microvascular complications observed under diabetic conditions.

Animals↗

PubMed2003

Inflammation, endothelial dysfunction, and the risk of high blood pressure: epidemiologic and biological evidence.

In spite of its high impact on cardiovascular and renal disease, knowledge on risk factors for the development of high blood pressure (HBP) is limited. Mild chronic inflammation may play a significant role in the incidence of HBP. A persistent low-grade inflammation state could be associated with high but within the 'normal range' cytokine plasma concentration. By impairing the capacity of the endothelium to generate vasodilating factors, particularly nitric oxide (NO), elevated cytokines may lead to the development of endothelial dysfunction, chronic impaired vasodilation, and HBP. These alterations in the L-arginine : NO pathway may play a major role in the development of HBP in young subjects, with inflammation-related alterations in the production of cyclo-oxygenase-derived vasoconstrictors becoming more prominent with advanced age. Cross-sectional independent associations between HBP and plasma levels of C-reactive protein, interleukin-6, and tissue necrosis factor alpha have been reported, but no prospective evidence of these associations is currently available.

Endothelium, Vascular↗

PubMed2005

Endothelial dysfunction and activation as an expression of disease: role of prostacyclin analogs.

The endothelium is now considered a real endocrine-paracrine organ, important not only as a structural barrier between the circulation and surrounding tissue, but also because it plays an essential role for local hemodynamics, releasing substances that modulate the vascular calibre and blood cell activation. Here, after a brief but detailed analysis of the importance of the endothelium in vascular homeostasis, in the control of coagulation and in the relations with the different blood cells, we will explain the concept of endothelial dysfunction (altered NO release) and activation (amplified adhesion molecule expression) in inflammatory, connective tissue and post-trasplantation diseases. Furthermore, this review will focus on the activity of prostacyclin and synthetic analogs, especially their ability to interact with the vasodilatation system and their role in modulating cell interaction by surface adhesion molecule expression, cytokines and growth factors release as well as gene transcription factors. Finally, we will consider the therapeutic role of prostacyclin analogs in the prevention and treatment of connective tissue diseases.

Connective Tissue Diseases↗

PubMed2001

Autoantibodies and endothelial dysfunction in well-controlled, uncomplicated insulin-dependent diabetes mellitus patients.

Patients with insulin-dependent diabetes mellitus (IDDM) are well known to be at high risk of vascular disease, and dysfunction of vascular endothelium is considered as an early step in the development of diabetic complications. Because of the involvement of autoimmunity in the pathogenesis of IDDM, our aim was to assess, in 45 IDDM patients without clinically evident vascular complications, whether early signs of endothelial cell dysfunction were correlated to alterations of the immune system. IDDM patients were characterized by significantly increased serum levels of C-reactive protein, of polymorphonuclear cells-derived elastase, of endothelin-1 (ET-1) and of thrombomodulin, while plasma concentrations of fibronectin (FNT) were significantly decreased, with a statistically significant inverse correlation between ET-1 and FNT values. The presence of circulating immune complexes (CIC) was investigated in 36 out of our 45 IDDM patients, and values above the cut-off were found in 17 (47.2%) of them. One-third of all patients showed values above the cut-off for IgG-aCL. In IDDM patients, at variance from the control group, the levels of ET-1 were directly correlated to those of von Willebrand factor, of anticardiolipin beta(2)-GPI and of CIC, with an inverse correlation with plasma FNT. An association between antiphospholipid antibodies and endothelial dysfunction and/or activation is therefore suggested, pointing to a synergism, in the early phases of IDDM vascular disease, between generation of autoantibodies and endothelial activation.

Adult↗

PubMed1993

Hypercholesterolemia promotes endothelial dysfunction in vitamin E- and selenium-deficient rats.

Abnormal regulation of local vascular tone occurs early in human and experimental atherosclerosis. Impaired endothelium-dependent vascular relaxations mediated by endothelium-derived relaxing factor are an important contributor to these abnormalities. Endothelium-derived relaxing factor is nitric oxide released as such or attached to a carrier molecule. Oxidized lipoproteins impede endothelium-derived relaxing factor-mediated responses in vitro. We designed in vivo experiments to determine whether hypercholesterolemia with and without deficiency of two endogenous lipid antioxidants, vitamin E and selenium, would result in endothelial dysfunction. Vitamin E and selenium deficiencies were induced in a group of hypertension-prone Dahl salt-sensitive rats fed a diet high in cholesterol (4%) but low in NaCl (0.5%) for 18 weeks. Two other groups of Dahl salt-sensitive rats received diets sufficient in vitamin E and selenium but containing either high or normal cholesterol levels (control group). Serum cholesterol levels increased approximately 10-fold in the two groups of rats fed high-cholesterol diets. Systolic blood pressure was 143 +/- 3 mm Hg in high-cholesterol/vitamin E- and selenium-sufficient rats and 142 +/- 5 mm Hg in high-cholesterol/vitamin E- and selenium-deficient rats (P = NS). Mild intimal thickening and occasional mononuclear cell infiltration were observed in both of these groups. Serum vitamin E levels were decreased, whereas serum thiobarbituric acid-reactive substances and exhaled pentane (two indicators of endogenous lipid oxidation) were significantly increased in high-cholesterol/vitamin E- and selenium-deficient rats compared with high-cholesterol/vitamin E- and selenium-sufficient rats.(ABSTRACT TRUNCATED AT 250 WORDS)

Acetylcholine↗

PubMed1991

Endothelial dysfunction in hypercholesterolemia is corrected by L-arginine.

Hypercholesterolemia attenuates endothelium-dependent vasorelaxation and augments the responses to vasoconstrictor agents. Both effects are largely due to a reduction in the release of endothelium-derived relaxing factor. Since endothelium-derived relaxing factor is now known to be nitric oxide derived from the metabolism of L-arginine, we hypothesized that the abnormal vascular response in hypercholesterolemia could be corrected by supplying the precursor to EDRF, L-arginine. In a series of studies, we have found that conduit and resistance vessels of hypercholesterolemic animals demonstrate endothelial dysfunction which is reversed after exposure to high concentrations of exogenous L-arginine. The experiments suggest that hypercholesterolemia induces a reversible dysfunction of arginine availability or metabolism.

Animals↗

PubMed2005

A nonthiazolidinedione peroxisome proliferator-activated receptor gamma agonist reverses endothelial dysfunction in diabetic (db/db-/-) mice.

We have previously reported that endothelium-dependent relaxation to acetylcholine is impaired in small mesenteric arteries from spontaneously diabetic (db/db) mice. The objective of the present study was to examine the effects of treatment of the db/db and the insulin-resistant ob/ob mice with the PPARgamma agonist 2-(2-(4-phenoxy-2-propylphenoxy)ethyl)indole-5-acetic acid (COOH). In the db/db model, an 8-week treatment with COOH (30 mg/kg/day) reduced plasma glucose from 48.0 +/- 2.5 (untreated) to 12.6 +/- 1.1 mM. In contrast, plasma glucose was not elevated in untreated ob/ob mice. Relaxation of small mesenteric arteries mediated by acetylcholine was impaired in the untreated db/db diabetic mice (51.7 +/- 7.4% maximal relaxation, n = 6) but not in the ob/ob mice (70.8 +/- 8.6% maximal relaxation, n = 3). This impairment was reversed with COOH treatment (86.9 +/- 0.4% maximal relaxation, n = 5). Malondialdehyde was elevated in plasma from diabetic db/db mice (13.9 +/- 1.1 versus 12.0 +/- 0.7 micromol/ml); however, when normalized to total cholesterol, no significant differences in the ratio of lipid peroxidation in plasma were identified. Western blot analysis and quantitative polymerase chain reaction for eNOS was performed on the isolated mesenteric vessels and revealed no differences in the relative levels of eNOS expression in diabetic and control animals; in addition, treatment with COOH had no significant effect on eNOS levels in either group. In summary, endothelial dysfunction and hyperglycemia were completely normalized in COOH-treated db/db mice. In contrast, nonhyperglycemic ob/ob mice exhibited normal vasodilatory responses to acetylcholine and, consequently, COOH treatment had no effect on endothelial function.

Acetates↗

PubMed2006

Ex vivo detection of rat coronary endothelial dysfunction in diabetes mellitus--methodological considerations.

The present state of knowledge unequivocally indicates that chronic diabetes is associated with impaired function of coronary vessels. Langendorff retrograde perfusion is one of the most frequently employed methods to study dysfunction of coronary vasculature in animal models of diabetes mellitus. However, because of methodological discrepancies in experimental protocols, the reliability of this technique is limited. In the current study, we propose the novel technique of vasoactive drug administration and aim to evaluate its usefulness in detecting coronary dysfunction in diabetes. Using Langendorff model, we compared the results of coronary endothelium-dependent (bradykinin) and -independent (diethylamine/nitric oxide, DEA/NO) vasodilatation obtained from experimental model utilizing automatically corrected-rate infusion with commonly used, constant-rate infusion of vasoactive drug. The infusion of bradykinin at constant rate failed to reveal coronary endothelium-dependent dysfunction typical for diabetes mellitus. Induction of endothelium-independent vasodilatation by constant infusion demonstrated augmented response in diabetic hearts. The administration of bradykinin or DEA/NO at the corrected rate was associated with significantly increased maximal responses in comparison with constant infusion experiments. This phenomenon was observed particularly in the control group. We conclude that only corrected-rate infusion of vasoactive agents to actual value of coronary flow enables the reliable detection of endothelial dysfunction in diabetes mellitus.

Animals↗