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Results for “endothelial dysfunction”

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At least 595 records · Page 33Linked to original sources

PubMed2001

Endothelial dysfunction and oxidative stress during estrogen deficiency in spontaneously hypertensive rats.

BACKGROUND: Postmenopausal estrogen deficiency is associated with an increased cardiovascular risk, hypertension, and oxidative stress. Angiotensin type 1 (AT(1)) receptor regulation is involved in the pathogenesis of atherosclerosis. To characterize vascular function, oxidative stress, and AT(1) receptor regulation during estrogen deficiency, ovariectomized spontaneously hypertensive rats (SHR) were investigated in comparison with sham-operated animals and with ovariectomized rats receiving estrogen replacement therapy with 17beta-estradiol. METHODS AND RESULTS: Arterial blood pressure was similar in all 3 groups investigated. Five weeks after ovariectomy, endothelial dysfunction in aortic rings was observed, which was reversed by estrogen replacement therapy. Estrogen deficiency led to an enhanced vasoconstriction by angiotensin II. Vascular superoxide production was significantly increased compared with that in sham-operated rats, as measured by lucigenin chemiluminescence assays. Estrogen substitution normalized the production of free radicals in the vessel wall. Vascular AT(1) receptor expression was significantly upregulated by estrogen deficiency, as shown by quantitative reverse transcription-polymerase chain reaction, whereas endothelial NO synthase mRNA expression and NO release were unchanged. Five-week treatment of the animals with the AT(1) receptor antagonist irbesartan prevented endothelial dysfunction in ovariectomized rats and normalized the vascular production of free radicals. CONCLUSIONS: In SHR, estrogen deficiency leads to increased vascular free radical production and enhanced angiotensin II-induced vasoconstriction via increased vascular AT(1) receptor expression, resulting in endothelial dysfunction. Estrogen replacement therapy and AT(1) receptor antagonism prevent these pathological changes. Therefore, estrogen deficiency-induced AT(1) receptor overexpression and oxidative stress may play an important role in cardiovascular diseases associated with menopause.

Angiotensin II↗

PubMed2004

Heme oxygenase-derived carbon monoxide promotes arteriolar endothelial dysfunction and contributes to salt-induced hypertension in Dahl salt-sensitive rats.

Vascular tissues express heme oxygenase (HO), which metabolizes heme to form carbon monoxide (CO). Heme-derived CO inhibits nitric oxide synthase and promotes endothelium-dependent vasoconstriction. After 4 wk of high-salt diet, Dahl salt-sensitive (Dahl-S) rats display hypertension, increased vascular HO-1 expression, and attenuated vasodilator responses to ACh that can be completely restored by acute treatment with an inhibitor of HO. In this study, we examined the temporal development of HO-mediated endothelial dysfunction in isolated pressurized first-order gracilis muscle arterioles, identified the HO product responsible, and studied the blood pressure effects of HO inhibition in Dahl-S rats on a high-salt diet. Male Dahl-S rats (5-6 wk) were placed on high-salt (8% NaCl) or low-salt (0.3% NaCl) diets for 0-4 wk. Blood pressure increased gradually, and responses to an endothelium-dependent vasodilator, ACh, decreased gradually with the length of high-salt diet. Flow-induced dilation was abolished in hypertensive Dahl-S rats. Acute in vitro pretreatment with an inhibitor of HO, chromium mesoporphyrin (CrMP), restored endothelium-dependent vasodilation and abolished the differences between groups. The HO product CO prevented the restoration of endothelium-dependent dilation by CrMP. Furthermore, administration of an HO inhibitor lowered blood pressure in Dahl-S rats with salt-induced hypertension but did not do so in low-salt control rats. These results suggest that hypertension and HO-mediated endothelial dysfunction develop gradually and simultaneously in Dahl-S rats on high-salt diets. They also suggest that HO-derived CO underlies the impaired endothelial dysfunction and contributes to hypertension in Dahl-S rats on high-salt diets.

Acetylcholine↗

PubMed2002

Endothelial dysfunction in chronic heart failure: clinical and therapeutic implications.

Chronic heart failure is a complex clinical syndrome in which abnormal vascular endothelial function has been shown to occur at both the experimental and clinical levels. Alterations in endothelial function may contribute to the increased vasomotor tone and to the vascular remodeling process observed in patients with chronic heart failure. Reduced shear stress, increased activity of the various vasoconstricting neurohormonal systems, and increased levels of proinflammatory cytokines promote endothelial dysfunction in chronic heart failure. This article summarizes the major mechanisms implicated in the pathophysiology of abnormal endothelial function in chronic heart failure, as well as the novel therapeutic interventions aimed at reducing endothelial dysfunction in patients with the syndrome.

Journal Article↗

PubMed2002

Mechanisms of amelioration of glucose-induced endothelial dysfunction following inhibition of protein kinase C in vivo.

Inhibition of protein kinase C (PKC) activity has been shown to improve the endothelial dysfunction associated with hyperglycemia and diabetes. The mechanisms by which inhibition of PKC activity ameliorates endothelial dysfunction in diabetes are not well understood. We investigated the relationship between PKC inhibition and leukocyte-endothelium interaction in the microcirculation of the rat mesentery exposed to 25 mmol/l D-glucose for 12 h. D-Glucose significantly increased leukocyte rolling and adherence in mesenteric postcapillary venules. This proinflammatory action of D-glucose was inhibited by superfusion of the mesentery with 30 nmol/l bisindolylmaleimide-I, a potent, selective PKC inhibitor (P < 0.01 vs. glucose alone after 90 min of superfusion). Immunohistochemical localization of the cell adhesion molecules P-selectin and intercellular adhesion molecule (ICAM)-1 on the endothelial cell surface was increased by 25 mmol/l D-glucose (P < 0.001 vs. control tissue from rats injected with saline), which was significantly reduced by bisindolylmaleimide-I (P < 0.001 vs. glucose alone). In addition, we studied adhesion of isolated neutrophils to rat superior mesenteric artery (SMA) vascular segments stimulated with 25 mmol/l D-glucose for 4 h in vitro. Pretreatment of the SMA vascular segments with either superoxide dismutase enzyme (100 units/ml) or bisindolylmaleimide-I (30 nmol/l) equally inhibited the increased neutrophil adherence to SMA endothelium in response to glucose. These data demonstrate that inhibition of PKC activity reduces leukocyte-endothelium interactions by suppressing surface expression of endothelial cell adhesion molecules in response to increased oxidative stress. These results provide a novel mechanism by which inhibition of PKC activity improves endothelial cell function in hyperglycemia and diabetes.

Animals↗

PubMed2001

Coronary vasodilation and improvement in endothelial dysfunction with endothelin ET(A) receptor blockade.

The endothelium-derived peptide endothelin-1 (ET-1) causes vasoconstriction predominantly via smooth muscle ET(A) receptor activation. We hypothesized that ET(A) receptor inhibition would improve human coronary vascular function. We studied unobstructed coronary arteries of 44 patients with atherosclerosis or its risk factors. Epicardial diameter (D) and Doppler flow velocity were measured, and coronary vascular resistance (CVR) was calculated during intracoronary infusions of acetylcholine (ACH) and sodium nitroprusside (SNP), and during cold pressor testing, before and after a 60-minute intracoronary infusion of the ET(A) receptor antagonist BQ-123. BQ-123 dilated the coronary circulation; D increased by 5.6+/-1.0% (P<0.0001), and CVR fell by 12+/-3% (P<0.01). The D response to ACH, corrected for the SNP response, improved in segments that constricted with ACH at baseline (P=0.03), whereas segments that initially dilated with ACH did not change with BQ-123 (P=NS). Improvement in D and CVR responses to ACH with BQ-123 inversely correlated with baseline ACH responses (r=-0.44 [P=0.006] and r=-0.78 [P=0.001], respectively), indicating greater improvement in those with endothelial dysfunction. Similarly, cold pressor testing-mediated epicardial vasoconstriction (-2.0+/-1.1%) was reversed after BQ-123 (+1.0+/-0.7%), especially in dysfunctional segments (from -5.6+/-0.9% to +2.2+/-0.9%, P<0.001). There was no correlation between any risk factor and the response to BQ-123. An arteriovenous difference in ET-1 levels developed after BQ-123, which was consistent with enhanced cardiac clearance of ET-1, probably via ET(B) receptors. Thus, ET-1 acting via the ET(A) receptor contributes to basal human coronary vasoconstrictor tone and endothelial dysfunction. This suggests that ET(A) receptor antagonism may have therapeutic potential in the treatment of endothelial dysfunction and atherosclerosis.

Acetylcholine↗

PubMed2005

Systemic markers of inflammation, endothelial dysfunction, and age-related maculopathy.

PURPOSE: To examine the association of systemic markers of inflammatory disease and endothelial dysfunction with age-related maculopathy (ARM). DESIGN: (1) Nested case-control analysis of prevalent ARM and (2) prospective analyses of incident ARM in a random sample of a population-based cohort. METHODS: Standardized protocols for blood collection, measurement of markers, administration of a questionnaire, and gradings of stereoscopic color fundus photography to determine ARM were used. Standard univariate and multivariate analyses were performed. participants: Included in the nested case-control study were 188 cases with moderate to advanced ARM and 195 controls matched for age, gender, and current smoking status at a baseline examination from 1988 to 1990, and living in Beaver Dam, Wisconsin. Included in the prospective analyses as a random sample of 321 persons were those who participated in a 5-year and/or 10-year follow-up. main outcome measures: Prevalent and incident ARM. RESULTS: Serum C-reactive protein, amyloid A, interleukin-6, tumor necrosis factor-alpha, intracellular adhesion molecule, E-selectin, folate, and Chlamydia pneumoniae IgG antibody were not associated with either prevalent or incident ARM. CONCLUSION: Contrary to other reports, we cannot confirm a strong or consistent relationship of markers of inflammation and endothelial dysfunction with ARM.

Adult↗

PubMed2004

Inhaled prostacyclin reduces cardiopulmonary bypass-induced pulmonary endothelial dysfunction via increased cyclic adenosine monophosphate levels.

OBJECTIVE: Cardiopulmonary bypass triggers a systemic inflammatory response that alters pulmonary endothelial function, which can contribute to pulmonary hypertension. This study was designed to demonstrate that inhaled prostacyclin, a selective pulmonary vasodilator prostaglandin, prevents pulmonary arterial endothelial dysfunction induced by cardiopulmonary bypass. METHODS: Three groups of Landrace swine were compared: control without cardiopulmonary bypass (control group); 90 minutes of normothermic cardiopulmonary bypass (bypass group); 90 minutes of cardiopulmonary bypass and treated with prostacyclin during cardiopulmonary bypass (continuous nebulization with continuous positive airway pressure until the end of the cardiopulmonary bypass; prostacyclin group). After 60 minutes of reperfusion, swine were put to death and pulmonary arteries harvested. After contraction to phenylephrine, endothelium-dependent relaxation to bradykinin and acetylcholine was studied in standard organ chamber experiments. The pulmonary artery intravascular cyclic adenosine monophosphate content was compared between the 3 groups (post-cardiopulmonary bypass). RESULTS: There was a statistically significant improvement of the endothelium-dependent relaxation to bradykinin in the prostacyclin group when compared with the bypass group (P <.05). There was no statistically significant difference for endothelium-dependent relaxation to acetylcholine (P >.05) between the prostacyclin and the bypass groups. There was a statistically significant decrease in the cyclic adenosine monophosphate content and a statistically significant increase of the mean pulmonary artery pressure in the bypass group only (P <.05). CONCLUSION: Prophylactic use of inhaled prostacyclin has a favorable impact on the pulmonary endothelial dysfunction induced by cardiopulmonary bypass associated with preservation of pulmonary intravascular cyclic adenosine monophosphate content and the pulmonary vascular tone.

Acetylcholine↗

PubMed2005

Indication of long-term endothelial dysfunction after sirolimus-eluting stent implantation.

AIMS: Endothelial dysfunction has been related both to progression of atherosclerotic disease and to future cardiovascular events. We assessed local epicardial endothelial function 6 months after sirolimus-eluting stent (SES) or bare metal stent (BS) implantation. METHODS AND RESULTS: In 12 patients (seven SES, five BS), endothelium-dependent vasomotion of a coronary segment 15 mm in length, starting 2 mm distal to the stent, was assessed with quantitative coronary angiography immediately after the procedure and at 6 months follow-up, after intracoronary infusion of acetylcholine. Intravascular ultrasound (IVUS) was performed and coronary flow reserve (CFR) assessed in all patients. At follow-up significant vasoconstriction was seen in SES (median 32% diameter reduction from baseline) but not in BS (median 2% reduction) patients after acetylcholine infusion (P=0.03 for SES vs. BS); endothelium-independent vasodilatation to nitrates did not differ significantly between groups (20% SES, 5% BS, P=0.14). IVUS revealed no late unhealed dissections and CFR was comparable between groups (SES 3.1 vs. BS 3.2, n.s.). CONCLUSION: SES implantation may have an adverse effect on local endothelium-dependent vasomotor responses compared with BS implantation at 6 months. Long-term clinical consequences of this observation are still unknown.

Aged↗

PubMed1997

Endothelial dysfunction in spontaneously hypertensive rats: consequences of chronic treatment with losartan or captopril.

BACKGROUND: Hypertension is associated with endothelial dysfunction characterized by decreased endothelium-dependent relaxations and increased endothelium-dependent contractions. Angiotensin converting enzyme inhibitors and thromboxane A2 receptor antagonists decreased the endothelium dysfunction in hypertensive animals. OBJECTIVE: To investigate the effects of prolonged treatment with losartan on endothelium-dependent and -independent relaxations and contractions in aortic rings from spontaneously hypertensive rats (SHR). MATERIAL AND METHODS: Male SHR aged 16 weeks were treated for 12 consecutive weeks either with 10 mg/kg losartan per day or with 60 mg/kg captopril per day administered via their drinking water. The systolic blood pressure was evaluated basally and during week 12. At the end of the treatment period, the vascular reactivity in aortic rings was studies. A group of rats treated with captopril was studies as a reference group. RESULTS: Losartan and captopril reduced the blood pressure significantly and comparably. Both drugs enhanced acetylcholine-induced relaxations and reduced the maximal contractile response to acetylcholine in the presence of NG-nitro-L arginine methyl ester (L-NAME). Contractile responses to phenylephrine, endothelin-l and U46619 were not affected by these treatments. Increased relaxing responses to superoxide dismutase were observed only in captopril-treated rats. Losartan reduced the contractile response to angiotensin II. By contrast this contractile response was elevated in rats treated with captopril. CONCLUSIONS: Prolonged antihypertensive treatments with losartan and captopril decreased the endothelial dysfunction in aortic rings from SHR not only by enhancing NO-dependent relaxations but also by reducing the contractions in response to an endothelium-derived contracting factor. The results further confirm that an endothelium-derived contracting factor plays a role in vascular dysfunction in SHR and the relationships between this factor and angiotensin II.

Acetylcholine↗

PubMed2003

Attenuation of homocysteine-induced endothelial dysfunction by exercise training.

Hyperhomocysteinemia is an independent risk factor for the development of cardiovascular disease. Exposure of endothelial cells to elevated levels of homocysteine (HCY) results in decreased availability of nitric oxide (NO) and impaired vascular function, both of which are early events in atherogenesis. Exercise training improves vascular function by increasing endothelial NO production secondary to an increase in the enzyme responsible for its synthesis, endothelial nitric oxide synthase (eNOS). We hypothesized that exercise training would increase endothelial NO production, which would attenuate the endothelial dysfunction associated with HCY exposure. Rats were randomly assigned to either sedentary (SED) or exercise (EX) groups. The exercise regimen consisted of treadmill running at 20-25 m/min, 15% grade, 30 min/day, 5 day/week for 6 weeks. Aortic rings obtained from SED and EX trained rats were incubated with 2 mM HCY for 120 min, then exposed to norepinephrine (NE 100 nM) to induce vasoconstriction. Once a stable contraction plateau was achieved, rings were exposed to increasing concentrations of the receptor-mediated endothelium-dependent vasodilator acetylcholine (ACh; 0.1, 1, 10, 100 nM). This procedure was repeated with the non-receptor-mediated endothelium-dependent vasodilator A-23187 (0.1, 1, 10, 100 nM), and the endothelium-independent vasodilator, NaNO(2) (0.1, 1, 10, 100 muM). In addition, eNOS protein content and eNOS enzyme activity were determined. Aortic rings obtained from exercise trained rats demonstrated significantly (P<0.05) greater relaxation to both ACh and A-23187 in comparison to aortic rings obtained from SED rats following exposure to HCY. Additionally, exercise training increased aortic eNOS protein content and activity. Our data demonstrate that exercise training improves endothelium-dependent vasorelaxation following HCY exposure and this may be due, at least in part, to elevated levels of eNOS protein and an increase in eNOS activity. These results suggest the possible role exercise may play in attenuating the endothelial dysfunction associated with hyperhomocysteinemia.

Journal Article↗

PubMed2003

Effect of angiotensin II type 1 (AT1) receptor antagonist on the endothelial dysfunction in spontaneously hypertensive rats in correlation with the nitric oxide system.

BACKGROUND: Hypertension is associated with impaired endothelial function, which can be explained by a decrease in nitric oxide (NO) generation or by an enhanced inactivation of NO after its release from endothelial cells. OBJECTIVES: The aim of this study was to investigate the effect of long-term treatment with losartan, an angiotensin II (AT1) receptor antagonist, on endothelial dysfunction in an animal model of hypertension in relation to the nitric oxide system. METHODS: Losartan was administered to 48 sixteen-week-old spontaneously hypertensive rats, in a dose of 10 mg/kg bw/daily in drinking water, for 12 weeks. Systolic blood pressure (SBP) was measured at the beginning, after 4, 8 and 12 weeks of treatment, by the tail-cuff plethysmographic method. At each mentioned time point, a group of 12 animals was sacrificed and blood was withdrawn from the abdominal aorta. Plasma samples were used for determination of total nitrate/nitirite levels, cyclic guanosine monophosphate (cGMP) and endothelin (ET) 1 levels. Statistical evaluation of the results was performed by the use of a computer statistical programme Statistica for Windows 5.0. RESULTS: Losartan produced a significant decrease of SBP at all time points. On the other hand, long-term treatment with this AT1 receptor antagonist produced a significant increase of nitrate/nitrite and cGMP plasma levels. When we compared the values of SBP with plasma nitrate/nitrite as well as with cGMP values, a statistically significant correlation was established. A statistically significant decrease in plasma endothelin 1 values was found during the whole study period. Also, a positive correlation between SBP and plasma endothelin 1 concentrations was observed. CONCLUSIONS: Long-term losartan (AT1 receptor antagonist) treatment, apart from its blood pressure lowering effect in hypertension, has beneficial effects on the endothelial dysfunction which is at least partially due to the activation of the nitric oxide system. (Tab. 1, Fig. 2, Ref. 33.)

Angiotensin II Type 1 Receptor Blockers↗

PubMed2005

[Pilot study of the noninvasive assessment of endothelial dysfunction by post-occlusion dopplerometry velocity curves analysis in arteria brachialis].

BACKGROUND: A new method of noninvasive assessment of endothelial dysfunction was used in this pilot study. Study has been set on a. brachialis dopplerometry velocity curves analysis. Index of blood stream deceleration between the first and second minute of the postocclusion periode was measured on a. brachialis after transient mechanical occlusion of the forearm--so called Deceleration Index. METHODS AND RESULTS: Eighteen patients with so far untreated hypercholesterolemia were involved in our study. Profile of velocity curves became significantly different after six months of fluvastatin therapy, Deceleration Index increased from 3 % to more than 7 % (p<0.05). That correlated with LDL-CH levels decrease, but also with the significant decrease of biochemical markers of endothelial dysfunction (trombomodulin, von Willebrand factor). CONCLUSIONS: The result is corresponding with previously published studies that have proved endothelial function improvement after statin therapy using another ultrasonographic methods.

Anticholesteremic Agents↗

PubMed2004

Endothelial dysfunction in patients with chronic heart failure is independently associated with increased incidence of hospitalization, cardiac transplantation, or death.

BACKGROUND: Endothelial dysfunction of coronary and peripheral arteries has been demonstrated in patients with chronic heart failure (CHF) and appears to be associated with functional implications. However, it is unknown whether endothelial dysfunction in CHF is independently associated with impaired outcome or progression of the disease. METHODS AND RESULTS: We assessed the follow-up of 67 consecutive patients with CHF [New York Heart Association (NYHA) functional class II-III] in which flow-dependent, endothelium-mediated vasodilation (FDD) of the radial artery was assessed by high resolution ultrasound. The primary endpoint was defined by cardiac death, hospitalization due to worsening of heart failure (NYHA class IV, pulmonary oedema), or heart transplantation. Cox regression analysis was used to determine whether FDD was associated with these heart failure-related events. During a median follow-up of 45.7 months 24 patients had an event: 18 patients were hospitalized due to worsening of heart failure or heart transplantation, six patients died for cardiac reasons. Cox regression analysis demonstrated that FDD (P<0.01), diabetes mellitus (P<0.01), and ejection fraction (P<0.01) were independent predictive factors for the occurrence of the primary endpoint. The Kaplan-Meier survival curve revealed a significantly better clinical outcome in patients with FDD above the median (6.2%) compared with those with FDD below the median (P<0.013). CONCLUSION: These observations suggest that endothelium-mediated vasodilation represents an independent predictor of cardiac death and hospitalization in patients with CHF, consistent with the notion that endothelium-derived nitric oxide may play a protective role in heart failure.

Chronic Disease↗

PubMed1999

C-reactive protein in healthy subjects: associations with obesity, insulin resistance, and endothelial dysfunction: a potential role for cytokines originating from adipose tissue?

C-reactive protein, a hepatic acute phase protein largely regulated by circulating levels of interleukin-6, predicts coronary heart disease incidence in healthy subjects. We have shown that subcutaneous adipose tissue secretes interleukin-6 in vivo. In this study we have sought associations of levels of C-reactive protein and interleukin-6 with measures of obesity and of chronic infection as their putative determinants. We have also related levels of C-reactive protein and interleukin-6 to markers of the insulin resistance syndrome and of endothelial dysfunction. We performed a cross-sectional study in 107 nondiabetic subjects: (1) Levels of C-reactive protein, and concentrations of the proinflammatory cytokines interleukin-6 and tumor necrosis factor-alpha, were related to all measures of obesity, but titers of antibodies to Helicobacter pylori were only weakly and those of Chlamydia pneumoniae and cytomegalovirus were not significantly correlated with levels of these molecules. Levels of C-reactive protein were significantly related to those of interleukin-6 (r=0.37, P<0.0005) and tumor necrosis factor-alpha (r=0.46, P<0.0001). (2) Concentrations of C-reactive protein were related to insulin resistance as calculated from the homoeostasis model assessment model, blood pressure, HDL, and triglyceride, and to markers of endothelial dysfunction (plasma levels of von Willebrand factor, tissue plasminogen activator, and cellular fibronectin). A mean standard deviation score of levels of acute phase markers correlated closely with a similar score of insulin resistance syndrome variables (r=0.59, P<0.00005), this relationship being weakened only marginally by removing measures of obesity from the insulin resistance score (r=0.53, P<0.00005). These data suggest that adipose tissue is an important determinant of a low level, chronic inflammatory state as reflected by levels of interleukin-6, tumor necrosis factor-alpha, and C-reactive protein, and that infection with H pylori, C pneumoniae, and cytomegalovirus is not. Moreover, our data support the concept that such a low-level, chronic inflammatory state may induce insulin resistance and endothelial dysfunction and thus link the latter phenomena with obesity and cardiovascular disease.

Adipose Tissue↗

PubMed2001

The effect of an Na+/H+ exchange inhibitor, SM-20550, on ischemia/reperfusion-induced endothelial dysfunction in isolated perfused rat hearts.

The aim of this study was to test the protective effect of an Na+/H+ exchange (NHE) inhibitor, SM-20550, on ischemia/reperfusion-induced endothelial dysfunction. Isolated rat hearts were subjected to 30 min of global ischemia followed by 20 min of reperfusion and their responses to the endothelial-dependent vasodilator, acetylcholine, and the endothelial-independent vasodilator, nitroglycerin, before and after ischemia were examined. Acetylcholine-induced relaxation was impaired after ischemia/reperfusion while nitroglycerin induced relaxation was not. Administration of 1-10 nmol/l SM-20550 [N-(aminoiminomethyl)-1,4-dimethyl-1H-indole-2-carboxamide methanesulfonic acid] before and after ischemia prevented impairment of acetylcholine-induced relaxation. To further understand the mechanism of SM-20550 in protecting endothelial function, we measured the inhibitory activity of SM-20550 on NHE in cultured endothelial cells. SM-20550 (1-100 nmol/l) inhibited recovery from acidosis induced by an NH4Cl prepulse in a concentration-dependent manner. Oxygen radicals from endothelial cells and leukocytes are one of the major sources of endothelial cell injury during ischemia and reperfusion. Consequently, we tested the effect of SM-20550 on H2O2-induced endothelial cell injury. SM-20550 (100-1,000 nmol/l) prevented H2O2-induced cell injury measured by lactate dehydrogenase assay. In conclusion, SM-20550 inhibited NHE in endothelial cells, protected ischemia/reperfusion-induced endothelial dysfunction and prevented H2O2-induced endothelial cell injury at higher concentrations.

Amidines↗

PubMed2005

Predictors of endothelial dysfunction in young women with polycystic ovary syndrome.

CONTEXT: Women with polycystic ovary syndrome (PCOS) may be at increased risk for cardiovascular disease. Endothelial dysfunction is an early marker of atherosclerosis. OBJECTIVES: The objectives of this study were to 1) compare endothelial function in young women with PCOS and regularly menstruating control women, and 2) to identify the determinants of endothelial function and investigate its relationship with body mass index in women with PCOS. DESIGN: This was a cross-sectional study. SETTING: This study was conducted at a tertiary cardiovascular research center. PATIENTS: Sixty-two young women with PCOS (mean age, 22.7 yr) and 17 control women, matched as a group for age and body mass index, were studied. Twenty-three women with PCOS were lean, 21 were overweight, and 18 were obese. MAIN OUTCOME MEASURES: Endothelium-dependent and -independent vascular function was assessed by measuring flow-mediated dilation (FMD) and nitrate-mediated dilation in the brachial artery (diameter change during hand hyperemia and after sublingual glyceryl trinitrate administration, respectively). RESULTS: FMD and nitrate-mediated dilation were significantly lower in PCOS than in control women (reduced by approximately 50 and 25%, respectively; both P < 0.0005). Insulin resistance, total testosterone, and total cholesterol were independent predictors of FMD, accounting for 21, 10, and 9% of the variance, respectively (P < 0.005 for all). A trend of deterioration in FMD from lean to overweight and obese PCOS women was observed, but differences among groups were not statistically significant. CONCLUSIONS: Women with PCOS have significant endothelial dysfunction at an early age (i.e. early 20s), and largely independent of obesity. This suggests that women with PCOS are at increased risk for early onset cardiovascular disease and may gain particular benefit from measures to improve endothelial function.

Adult↗

PubMed2004

Ventilation prevents pulmonary endothelial dysfunction and improves oxygenation after cardiopulmonary bypass without aortic cross-clamping.

OBJECTIVE: Endothelial dysfunction of the pulmonary arterial tree occurring after cardiopulmonary bypass (CPB) contributes to pulmonary hypertension and respiratory failure in the postoperative period. The goal of the present study was to characterize the alterations of endothelial cell signal transduction pathways in pulmonary arteries following CPB, the effect of ventilation and nitric oxide (NO) inhalation on endothelium-dependent relaxations and the alterations in hemodynamics and oxygenation. METHODS: Six groups of Landrace swine were compared: control, sham without CPB, CPB 150min+no reperfusion, CPB 150min+reperfusion 60 min, CPB 150min+ventilation (tidal volume 12 ml/kg)+reperfusion 60 min, and CPB 150min+NO inhalation (with ventilation, NO 40 ppm)+60 min of reperfusion. No cross-clamping was applied, the heart was left beating, empty. Pulmonary artery reactivity was evaluated in organ chambers to assess the endothelium-dependent relaxations. RESULTS: CPB alone did not alter endothelial function. CPB and pulmonary reperfusion induced a statistically significant decrease in endothelium-dependent relaxations to acetylcholine. Mechanical ventilation during CPB prevented the reduction of relaxations to acetylcholine. Ventilation and NO inhalation during CPB did not differ from ventilation alone in terms of endothelium-dependent relaxations. There were no differences between groups for relaxations to bradykinin. There was a significant increase in arterial oxygen tension in the ventilated group compared to the non-ventilated group. CONCLUSION: Pulmonary reperfusion after CPB causes a selective dysfunction of Gi-protein-mediated relaxations. Mechanical ventilation prevents the pulmonary endothelial dysfunction due to reperfusion after CPB. Ventilation also improves oxygenation after CPB. Mechanical ventilation could be used as a preventive approach for patients undergoing cardiac surgery with extracorporeal circulation.

Administration, Inhalation↗

PubMed2002

Mental stress induces prolonged endothelial dysfunction via endothelin-A receptors.

BACKGROUND: Mental stress is a risk factor for atherosclerosis and may precipitate myocardial ischemia and infarction. Because endothelial dysfunction is an early manifestation of atherosclerosis, we investigated the impact of mental stress on endothelial function. Methods and Results- The effects of a 3-minute mental stress task on endothelium-dependent vasodilation were studied in healthy subjects without cardiovascular risk factors. Flow-mediated (FMD) and nitroglycerin (0.4 mg sublingual)-induced vasodilation were studied before and after mental stress by high-resolution ultrasound of the radial artery. Additionally, FMD was assessed before and 10 to 45 minutes after mental stress during intraarterial infusion of a selective endothelin A receptor antagonist (BQ-123, 1 nmol/min) or saline, respectively. Endothelium-dependent vasodilation was reduced by half for about 45 minutes (8.0+/-1.1% versus 4.1+/-1.0%; P<0.002), whereas endothelium-independent vasodilation to nitroglycerin remained unaffected (15.6+/-1.6 versus 14.3+/-1.3%; NS). Intraarterial infusion of BQ-123, a selective endothelin-A receptor antagonist, but not saline prevented the impairment of endothelium-dependent vasodilation (8.6+/-1.2 versus 9.4+/-1.3%; NS). In contrast, intraarterial infusion of norepinephrine of similar duration as mental stress did not inhibit FMD. CONCLUSIONS: Mental stress induces prolonged endothelial dysfunction, which is prevented by selective endothelin-A receptor antagonism. This represents a novel and important link between mental stress and atherosclerotic vascular disease.

Adult↗