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PubMed2001

Long-term effect of bilateral ovariectomy on endothelial function in aortic rings of spontaneously hypertensive rats: role of nitric oxide.

Endothelial dysfunction associated with both menopause and hypertension could be one of the possible explanations for increased cardiovascular morbidity and mortality in hypertensive postmenopausal women. The aim of the present study was to investigate the long-term effect of menopause (bilateral ovariectomy) on endothelial function in isolated aortic rings of spontaneously hypertensive rats (SHR). Aortic rings were suspended in organ chambers filled with physiological salt solution (95% O2, 5% CO2, 37 degrees C), and isometric tension was measured. In studies designed to assess the tone-related release of nitric oxide (NO) from phenylephrine-precontracted aortic rings, we found that vasoconstriction induced by L-NAME was greater in aortic rings from sham-ovariectomized SHR (SHAM SHR) than in those obtained from ovariectomized SHR (OVX SHR). Concentration-related relaxant responses to superoxide dismutase were significantly greater in the SHAM SHR than in the OVX SHR. In contrast, receptor-mediated release of NO was not altered by ovariectomy, as deduced from acetylcholine (ACh) concentration-responses curves. Responses to the exogenous NO donor sodium nitroprusside (SNP) were also identical in both ovariectomized and sham-ovariectomized groups, ruling out differences in smooth muscle reactivity to NO. These results show that NO release is impaired in OVX SHR, an animal model of simultaneous hypertension and menopause.

Acetylcholine↗

PubMed2005

Effect of palm oil on blood pressure, endothelial function and oxidative stress.

The pathogenesis of hypertension has been associated with endothelial dysfunction and oxidative stress. We have previously shown that palm oil (PO), with an unsaturated-to-saturated fatty acid ratio close to one and rich in antioxidants vitamins, reduces oxidative stress-induced hypertension in normal rats. Here, we investigated the cardiovascular effects of natural vitamin-rich PO using the Dahl Salt-sensitive hypertension model. Male rats were fed either a high salt (8%NaCl, HS) or low salt (0.3% NaCl, LS) diet with or without PO (Carotino, 5 g/kg daily) for four weeks. Mean arterial pressure (MAP), heart rate, blood flow and vascular resistance, vascular reactivity in vitro as well as remodelling of second-order mesenteric arteries were measured. Plasma levels of nitric oxide (NO), prostacyclin, thromboxane A(2) (TXA(2)) and isoprostane (ISO), were determined by enzyme immunoassay. Plasma, heart and kidney GSH and GSSG levels were analyzed by HPLC and aortic superoxide ((.)O(2)-) production by fluorescence spectrometry. High salt induced an elevation in MAP that was associated with decreased NO, prostacyclin and GSH: GSSG ratio. Plasma ISO and TXA(2), aortic and renal vascular resistance as well as aortic (.)O(2)- were increased. Palm oil reduced MAP, plasma TXA(2) and vascular resistance of the renal and aortic arteries, and increased the GSH: GSSG ratio and NO in the LS group. The HS-induced elevation in ISO and (.)O(2)- production and the reductions in kidney GSH: GSSG ratio, were attenuated by PO. The effect of PO was also associated with a reduced vessel wall-thickness: lumen diameter ratio and a greater relaxant effect of mesenteric arteries to acetylcholine, in the LS group. The mortality associated with HS was reduced by PO. Thus, palm oil attenuates the progression of salt-induced hypertension and mortality, via mechanisms involving modulation of endothelial function and reduction in oxidative stress.

Animals↗

PubMed1996

Physical training improves endothelial function in patients with chronic heart failure.

BACKGROUND: Chronic heart failure is associated with endothelial dysfunction including impaired endothelium-mediated, flow-dependent dilation (FDD). Since endothelial function is thought to play an important role in coordinating tissue perfusion and modulating arterial compliance, interventions to improve endothelial dysfunction are imperative. METHODS AND RESULTS: To assess the potential of physical training to restore FDD, 12 patients with chronic heart failure were studied and compared with FDD of 7 age-matched normal subjects. With a recently developed high-resolution ultrasound system, diameters of radial artery were measured at rest, during reactive hyperemia (with increased flow causing endothelium-mediated dilation), and during sodium nitroprusside, causing endothelium-independent dilation. Determination of FDD was repeated after intra-arterial infusion of NG-monomethyl-L-arginine (L-NMMA, 7 mumol/min) to inhibit endothelial synthesis and release of nitric oxide. The protocol was performed at baseline, after 4 weeks of daily handgrip training, and 6 weeks after cessation of the training program. FDD was impaired in heart failure patients compared with normal subjects. L-NMMA attenuated FDD, indicating that the endothelial release of nitric oxide is involved in FDD. Physical training restored FDD in patients with heart failure. In particular, the portion of FDD inhibited by L-NMMA (representing FDD mediated by nitric oxide) was significantly higher after physical training (8-minute occlusion: 8.0 +/- 1% versus 5.4 +/- 0.9%; P < .05; normal subjects: 9.2 +/- 1%). CONCLUSIONS: These results indicate that physical training restores FDD in patients with chronic heart failure, possibly by enhanced endothelial release of nitric oxide.

Adult↗

PubMed2000

Endothelial function as a therapeutic target in coronary artery disease.

In healthy individuals, endothelial cells regulate a host of functions including vasomotor tone, thrombosis/ fibrinolysis, and cell-cell interactions. The development of endothelial dysfunction may be a common pathway by which cardiovascular risk factors impact plaque formation, growth, and rupture. Many pharmacologic and nonpharmacologic interventions known to decrease cardiovascular risk also improve endothelial function. For these reasons, some have suggested that improvement in endothelial function may be an important therapeutic target in the treatment of coronary artery disease.

Angiotensin-Converting Enzyme Inhibitors↗

PubMed1999

Impairment of endothelial functions by acute hyperhomocysteinemia and reversal by antioxidant vitamins.

CONTEXT: Increased levels of homocysteine are associated with risk of cardiovascular disease. Homocysteine may cause this risk by impairing endothelial cell function. OBJECTIVE: To evaluate the effect of acute hyperhomocysteinemia with and without antioxidant vitamin pretreatment on cardiovascular risk factors and endothelial functions. DESIGN AND SETTING: Observer-blinded, randomized crossover study conducted at a university hospital in Italy. SUBJECTS: Twenty healthy hospital staff volunteers (10 men, 10 women) aged 25 to 45 years. INTERVENTIONS: Subjects were given each of 3 loads in random order at 1-week intervals: oral methionine, 100 mg/kg in fruit juice; the same methionine load immediately following ingestion of antioxidant vitamin E, 800 IU, and ascorbic acid, 1000 mg; and methionine-free fruit juice (placebo). Ten of the 20 subjects also ingested a placebo load with vitamins. MAIN OUTCOME MEASURES: Lipid, coagulation, glucose, and circulating adhesion molecule parameters, blood pressure, and endothelial functions as assessed by hemodynamic and rheologic responses to L-arginine, evaluated at baseline and 4 hours following ingestion of the loads. RESULTS: The oral methionine load increased mean (SD) plasma homocysteine level from 10.5 (3.8) micromol/L at baseline to 27.1 (6.7) micromol/L at 4 hours (P<.001). A similar increase was observed with the same load plus vitamins (10.0 [4.0] to 22.7 [7.8] micromol/L; P<.001) but no significant increase was observed with placebo (10.1 [3.7] to 10.4 [3.2] micromol/L; P=.75). Coagulation and circulating adhesion molecule levels significantly increased after methionine ingestion alone (P<.05) but not after placebo or methionine ingestion with vitamins. While the mean (SD) blood pressure (-7.0% [2.7%]; P<.001), platelet aggregation response to adenosine diphosphate (-11.4% [4.5%]; P=.009) and blood viscosity (-3.0% [1.2%]; P=.04) declined in these parameters 10 minutes after an L-arginine load (3 g) following placebo, the increase after methionine alone (-2.3% [1.5%], 4.0% [3.0%], and 1.5% [1.0%], respectively; P<.05), did not occur following methionine load with vitamin pretreatment (-6.3% [2.5%], -7.9% [3.5%], and -1.5% [1.0%], respectively; P=.24). CONCLUSION: Our data suggest that mild to moderate elevations of plasma homocysteine levels in healthy subjects activate coagulation, modify the adhesive properties of endothelium, and impair the vascular responses to L-arginine. Pretreatment with antioxidant vitamin E and ascorbic acid blocks the effects of hyperhomocysteinemia, suggesting an oxidative mechanism.

Acute Disease↗

PubMed2005

[Change in endothelial progenitor cells and endothelial function in patients with unstable angina pectoris].

OBJECTIVE: To investigate the relationship between endothelial progenitors cells (EPCs) and endothelium-dependent vasodilation in patients with unstable angina pectoris. METHODS: Thirty patients with unstable angina pectoris (UAP) and thirty control subjects were recruited. Flow-mediated dilation (FMD) in the brachial artery was evaluated by using ultrasound Doppler flow method. The number of circulating EPCs was analyzed by flow cytometry analysis. Total mononuclear cells were isolated from peripheral blood by Ficoll density gradient centrifugation, and then the cells were plated on fibronectin-coated culture dishes. CD34 antigen of adherent cells was identified by immunohistochemical assay. EPCs were characterized as adherent cells double positive for FITC-UEA-I binding and DiI-acLDL uptake by direct fluorescent staining under inverted fluorescent microscope. RESULTS: FMD was significantly impaired in the UAP group compared with the control group (5.93% +/- 2.67% vs 11.1% +/- 4.36%, P < 0.05). There was no significant difference in NMD between two groups (13.60% +/- 5.03% vs 14.18% +/- 4.50%, P > 0.05). The number of CD34(+) cells significantly increased in the UAP group compared with the control group (0.13% +/- 0.05% vs 0.09% +/- 0.04%, P < 0.05). There was a negative association between impaired FMD and increased CD34(+) cell (r = -0.385, P < 0.05). A positive antigen of CD34 of adhesion cells and double positive adhesion cells were found. CONCLUSION: This study shows that the levels of peripheral CD34(+) cells in patients with UAP increase with an impaired endothelial function. The increase in EPCs may be an important compensatory response to acute coronary ischemia and impaired endothelium in patients with UAP.

Aged↗

PubMed2005

Endothelial function and dysfunction. Part I: Methodological issues for assessment in the different vascular beds: a statement by the Working Group on Endothelin and Endothelial Factors of the European Society of Hypertension.

An enormous number of studies in the last two decades have been devoted to investigating the role of the endothelium in cardiovascular diseases. Nonetheless, the optimal methodology for investigating the multifaceted aspects of endothelial dysfunction is still under debate. Biochemical markers, molecular genetic tests and invasive and non-invasive tools with and without pharmacological and physiological stimuli have been introduced. Furthermore newer pharmacological tools have been proposed. However, the application of these methodologies should fulfil a number of requirements in order to provide conclusive answers in this area of research. Thus, the most relevant methodological issues in the research on endothelial function and dysfunction are summarized in this paper.

Endothelium, Vascular↗

PubMed1996

Impaired haemostatic kinetics and endothelial function in Behçet's disease.

OBJECTIVES: This study was planned to explore the alterations of endothelial functions in the prethrombotic state of Behçet's disease (BD) patients. DESIGN: Plasma levels of endothelial secretory markers, in vivo molecular haemostatic and fibrinolytic parameters were cross-sectionally determined in the study group. SETTING AND SUBJECTS: In our tertiary referral centre, 30 (13 men, 17 women) BD patients, mean age 31 +/- 7 years, and 15 (eight men, seven women) healthy volunteers, mean age 26 +/- 9 years, were eligible for inclusion in the study after obtaining their written consents. INTERVENTIONS: All plasma samples for the assays of haemostatic parameters were obtained before and after an endothelial stimulant, desmopressin acetate (DDAVP). RESULTS: We have shown that in the procoagulant phase of BD patients: (1) basal thrombomodulin concentrations are increased and could not be provoked by DDAVP infusion; (2) both thromboxane B2 and 6-keto prostaglandin F1 alpha increments occur concurrently; (3) in vivo coagulation markers are elevated and raised plasmin-alpha 2 antiplasmin complex indicates a subclinical concomitant fibrinolysis; (4) the fibrinolytic process is conveyed in a somewhat complex manner in which plasminogen activator binding kinetics might be also altered. CONCLUSIONS: Endothelial cell injury, augmented thrombotic risk with compensatory excessive fibrinolysis and alterations in endothelial cell receptor-fibrinolytic marker relations might take place in the pathogenesis and thereby modulate the natural course of haemostatic processes of BD.

Adult↗

PubMed2002

Influence of estrogen on aortic stiffness and endothelial function in female rats.

Mechanisms underlying cardioprotective properties of estrogens are not fully understood. We evaluated effects of ovariectomy and estrogen replacement on arterial distensibility and endothelial function in rats. Sprague-Dawley rats were sham operated (Sham) or ovariectomized and treated with 17beta-estradiol (OVX-E(2)) or vehicle (OVX) for 3 wk. Anesthetized rats were instrumented for measurement of central and peripheral arterial blood pressures and carotid and hindquarters blood flows. Arterial distensibility was evaluated in anesthetized rats on the basis of changes in thoracoabdominal pressure pulse wave velocity (PWV). PWV was calculated as the distance between the two central and peripheral cannula tips divided by transit time. Ovariectomy significantly reduced PWV (390 +/- 19 and 472 +/- 42 cm/s in OVX and Sham, respectively). Estrogen treatment completely normalized PWV (490 +/- 37 cm/s). Estrogen-treated rats were associated with left ventricular hypertrophy and increased pulse pressure. Resting hemodynamic parameters were similar in all groups. Estrogen replacement significantly potentiated bradykinin vasodilatory responses in the hindlimb, but not in the carotid vascular bed. Hemodynamic responses to sodium nitroprusside and ANG II were similar in all groups. In conclusion, our results demonstrate for the first time that aortic stiffness determined by PWV is decreased in estrogen-deficient rats. Estrogen treatment increases aortic stiffness and potentiates endothelial vasodilator function in the hindquarters, but not in the carotid vascular bed, suggesting a regional heterogeneity in the modulatory influence of estrogen on vasomotor function.

Anesthesia↗

PubMed2002

Endothelial function is preserved in pregnant women with well-controlled type 1 diabetes.

OBJECTIVE: Pregnant women with diabetes mellitus have a higher incidence of adverse pregnancy outcomes. Vascular, and in particular, endothelial function may be significantly modified in diabetes resulting in impaired endothelium-dependent relaxation. This study aims to investigate endothelium-dependent relaxation in pregnant women with pre-existing type I diabetes mellitus. METHODS: Small arteries (mean luminal diameter approximately 295 microm) were isolated from biopsies of subcutaneous fat from pregnant women with pre-existing type I diabetes mellitus, non-diabetic pregnant women, and non-diabetic non-pregnant women. Endothelial and smooth muscle function were determined using wire myography, and the contributions of nitric oxide, vasodilator prostanoid and endothelial hyperpolarisation were studied using specific inhibitors. RESULTS: Arteries obtained from the diabetic pregnant women did not demonstrate any difference in either endothelial or smooth muscle function when compared with non-diabetic pregnant women. The contribution of nitric oxide to endothelium-dependent relaxation was approximately 20% in the pregnant women regardless of whether they were diabetic, and approximately 11% in the non-pregnant women. Endothelial hyperpolarisation appeared to contribute largely to vasorelaxation in human subcutaneous arteries, and was at least twice that of nitric oxide in pregnant women and fivefold greater in non-pregnant women. CONCLUSIONS: This study provides evidence that pregnant women with well-controlled pre-existing type 1 diabetes mellitus have both normal endothelial and smooth muscle function. Endothelium-dependent hyperpolarisation appears to play a large role in vascular relaxation in human subcutaneous resistance arteries. This study suggests that the problems associated with diabetic pregnancies are unlikely to be due to vascular dysfunction.

Adult↗

PubMed1995

Coronary artery endothelial function after myocardial ischemia and reperfusion.

BACKGROUND: The consequences of ischemia-reperfusion injury on myocytes has been studied intensely, and previous investigations of methods of myocardial protection during global and regional ischemia have focused on resultant alterations in myocardial function. However, the coronary artery endothelium is also vulnerable to damage, and only recently have investigators been able to assess coronary endothelial function. METHODS: This review examines some aspects of coronary flow abnormalities that occur after ischemia and reperfusion. In addition, we summarize recent data that address the hypothesis that injury to the coronary artery endothelium may contribute to the pathophysiology of global (and regional) cardiac ischemia and reperfusion. RESULTS: It appears that ischemia and reperfusion selectively injure a component in the receptor/G-protein complex linking receptor-stimulus coupling to the activation of nitric oxide synthase. Further, oxygen radicals may contribute to this injury. Recent investigations demonstrate that oxygen radicals impair the receptor/G-protein complex specific to the nitric oxide signal transduction pathway rather than causing global receptor/G-protein dysfunction. CONCLUSIONS: The understanding of endothelial cell function and the elucidation of the nitric oxide pathway should further clarify our understanding of the pathogenesis of endothelial reperfusion injury and coronary vasospasm and contribute to the development of effective therapeutic interventions.

Amino Acid Oxidoreductases↗

PubMed2004

Treating hypothyroidism improves endothelial function.

Hypothyroidism patients have increased cardiovascular risk, although the mechanism is not defined. Endothelial dysfunction may initiate atherosclerosis, is present in patients with hypothyroidism, and therefore may link hypothyroidism and vascular disease. We are unaware of studies examining the effect of thyroid replacement therapy on endothelial function in hypothyroid patients. The present study examined the effect of treatment of hypothyroidism on brachial artery reactivity. Consequently, we measured endothelium-dependent (EDV) and endothelium-independent (EIV) vasodilation using brachial artery ultrasonography in 8 hypothyroid patients (5 men, mean age 48.9 +/- 5.5 years; mean thyrotropin [TSH] 49.0 +/- 37.0 mIU/L) before and after thyroxine treatment. Thyroxine treatment reduced average TSH to 2.9 +/- 0.5 mIU/L and improved EDV (8.0% +/- 4.4% v 3.4% +/- 2.5%, P <.05), whereas EIV was unchanged (20.3% +/- 6.1% v 19.2% +/- 9.4%, P = not significant [NS]). Thyroxine treatment did not alter serum lipids. Thyroid replacement therapy improves endothelium-dependent vascular reactivity in patients with hypothyroidism irrespective of lipid changes.

Adult↗

PubMed2001

Improved preservation of coronary endothelial function with Celsior compared with blood and crystalloid solutions in heart transplantation.

BACKGROUND: Endothelial injury from preservation solutions has been implicated in acute coronary vasospasm and pathologic activation of the endothelium, which can contribute to the development of graft coronary vasculopathy after heart transplantation. Preservation solutions with a powerful antioxidant capacity may decrease the occurrence of these complications. MATERIALS AND METHODS: This study was designed to evaluate the effect of Celsior (an anti-oxidant solution specifically designed for cardiac preservation) in a model of heart preservation (4 hours at 4 degrees C to reproduce the situation encountered in clinical heart transplantation) compared two commonly used cardioplegic and preservation strategies on coronary endothelial function. Endothelium-dependent relaxation of normal porcine epicardial coronary arteries to serotonin (5-HT, an agonist that activates 5-HT(1d) receptors coupled to Gi proteins) and bradykinin (BK, which activates B2 receptors coupled to Gq proteins) was studied in standard organ chamber experiments in the following groups: a control group was submitted to immediate excision without cardioplegia and preserved in saline solution (0.9% NaCl) for 4 hours (Group 1); two groups had cardioplegia induced with a crystalloid solution and were stored for 4 hours in saline (Group 2) or 4 hours in Celsior solution (Group 3); and two groups had cardioplegia induced with normothermic blood cardioplegia and were stored for 4 hours in the saline (Group 4), or 4 hours in Celsior solution (Group 5). Finally, two groups underwent cardioplegia with Celsior and were stored for 4 hours in saline (Group 6), or 4 hours in the Celsior solution (Group 7). All cardioplegia solutions were at 4 degrees C (except blood cardioplegia at 37 degrees C) and all preservations solutions were at 4 degrees C. RESULTS: Endothelium-dependent relaxations to serotonin were significantly decreased in all groups except the Celsior + Celsior group compared with the control group. There were no significant differences in relaxation to bradykinin except in one group. Use of the Celsior solution for induction of cardioplegia and storage better preserved endothelium-dependent G-protein-mediated relaxation compared with the other arrest and preservation strategies. CONCLUSIONS: The observed effect may be associated with an improvement in both short- and long-term outcome in heart transplantation, especially because these alterations may be further compounded by reperfusion.

Animals↗

PubMed2000

Adverse endothelial function and the insulin resistance syndrome.

Type 2 diabetes is characterized by impaired endothelial dependent vasodilatation which may contribute to the high prevalence of vascular disease in such patients. Although hyperglycaemia, dyslipidaemia and hypertension can all independently cause a similar defect, recent data suggest that endothelial dysfunction may be intrinsic to the insulin resistance syndrome that commonly precedes type 2 diabetes. Such abnormalities in endothelial function could represent the impact of subclinical disturbance of metabolism or alternatively the presence of a common cellular defect that influences both nitric oxide bioavailability and insulin mediated glucose disposal. Resolution of this puzzle is likely to lead to important advances in our knowledge and ultimately treatment of vascular disease.

Adult↗

PubMed2003

Oral L-arginine improves endothelial function in healthy individuals older than 70 years.

Ageing is associated with progressive endothelial dysfunction in normal humans. Flow-mediated dilation (FMD) of the brachial artery is impaired in elderly individuals with cardiovascular disease and vascular nitric oxide (NO) bioavailability is reduced. We investigated whether oral L-arginine, the substrate for NO synthesis, can improve impaired FMD in healthy very old people. In a prospective, double-blind, randomized crossover trial, 12 healthy old subjects (age 73.8 +/- 2.7 years) took L-arginine (8 g p.o. two times daily) or placebo for 14 days each, separated by a wash-out period of 14 days. FMD was determined by high-resolution ultrasound in the brachial artery during reactive hyperaemia. Baseline artery diameter was 3.88 +/- 0.18 mm. L-Arginine significantly improved FMD (to 5.7 +/- 1.2%, p < 0.0001), whereas placebo had no effect (-0.25 +/- 0.7%; n.s.). After L-arginine, plasma levels of L-arginine increased significantly (114.9 +/- 11.6 versus 57.4 +/- 5.0 micromol/l), but placebo had no effect. As NO synthesis can be antagonized by its endogenous inhibitor asymmetric dimethyl L-arginine (ADMA), we determined ADMA plasma concentrations, which were elevated at baseline in comparison to healthy middle-aged individuals (3.9 +/- 0.2 versus 1.0 +/- 0.1 micromol/l; p < 0.0001). ADMA remained unchanged during treatment, but L-arginine supplementation normalized the L-arginine/ADMA ratio (p < 0.05). We conclude that in healthy very old age endothelial function is impaired and may be improved by oral L-arginine supplementation, probably due to normalization of the L-arginine/ADMA ratio.

Administration, Oral↗

PubMed1998

Impairment of endothelial function induced by glyc-oxidized lipoprotein a [Lp(a)].

UNLABELLED: Diabetic patients develop endothelial dysfunction early in the course of the disease. Atherogenic lipoproteins such as LDL and Lp(a) are important risk factors for endothelial dysfunction and undergo nonenzymatic glycation in hyperglycaemia. Here we assessed whether glycation of Lp(a) potentiates its damaging influence on endothelial function. Human Lp(a) was glycated by dialyzation for 7 days against buffer containing 200 mmol/l glucose, or sham-treated without glucose and oxidized by incubation with Cu++. The degree of glycation accounted to 32 +/- 4%, and glycation rendered Lp(a) more susceptible to oxidative modification when exposed to Cu++. Isolated rings of rabbit aorta were superfused with physiological salt solution, and isometric tension was recorded. Incubation of the aortic rings with sham-treated or with 30 microg/ml glycated Lp(a), not oxidized, had no influence on acetylcholine-induced, endothelium-dependent relaxation. Exposure of the aortic rings to 30 microg/ml oxidized non-glycated (ox) Lp(a) caused a significant inhibition (19% at 1 microM acetylcholine) of the endothelium-dependent relaxation. Incubation of aortic rings with 30 microg/ml oxidized glycated (glyc-ox) Lp(a) attenuated endothelium-dependent relaxation more potently than oxLp(a) (by 34% at 1 microM acetylcholine). The presence of diethyl-dithio-carbamate (DDC), an inhibitor of the endogenous superoxide dismutase (SOD), potentiated the inhibition of relaxation induced by oxLp(a) and by glyc-oxLp(a) [38% inhibition at 1 microM acetylcholine for oxLp(a), and 49% inhibition at 1 microM acetylcholine for glyc-oxLp(a)]. Co-incubation with the O2- scavenger 4,5-dihydroxy-1,3-benzene disulfonic acid disodium salt (TIRON) prevented the inhibition of relaxation by the oxidized lipoproteins, suggesting that enhanced NO-inactivation by O2- could be the underlying mechanism for the impairment of endothelium-dependent dilations by ox- and glyc-oxLp(a). The concentration of lysophosphatidycholine, a lipoprotein oxidation product and stimulus for O2- formation, was significantly enhanced in oxLp(a) and in glyc-oxLp(a) compared to native lipoproteins. CONCLUSION: Glycation enhances the endothelium-damaging influence of oxLp(a), presumably by enhancing oxidative stress. The likely mechanism for attenuation of endothelium-dependent dilations is increased formation of O2-, resulting in inactivation of nitric oxide. This mechanism may play an important role in diabetic patients and may contribute to disturbed organ perfusion.

1,2-Dihydroxybenzene-3,5-Disulfonic Acid Disodium ↗

PubMed2002

Saline containing phosphatidylcholine liposomes possess the ability to restore endothelial function damaged resulting from gamma-irradiation.

The protective action of passive saline filled ("empty") phosphatidylcholine liposomes (PCL) on endothelial function was examined in thoracic aortas obtained from gamma irradiated (6 Gy) Chinchilla rabbits, and then verified in experiments on non-anesthetized and anesthetized rats. Acetylcholine (ACh)-induced vascular relaxant responses in isolated vascular tissues rats were used as the test of endothelial integrity and its functional ability. It was shown that when added to the bath solution (100 microg/ml), PCL effectively restored endothelium-dependent ACh relaxations of isolated vascular rings damaged resulting from gamma-irradiation but had no effect on endothelium-independent vascular responses to therapeutic nitric oxide (NO) donors. The liposomes were also without protective effect when injected to the rabbits intraperitoneally (30 mg/kg) 1 hour before irradiation. In contrast, PCL, being injected at the same dose 1 hour after radiation impact, promote normalization of both endothelium-dependent vascular responses to ACh and nitric oxide (NO) donors. PCL restored also the sensitivity of vascular tissues to authentic NO (aqueous NO solution) that was surprisingly increased after irradiation, and normalized relationship between ACh-stimulated NO release and relaxant response amplitudes in irradiated aortas. Experiments on non-anesthetized and anesthetized rats demonstrated that irradiation led to significant elevation in the level of arterial blood pressure without any changes in cardiac contractility. PCL administration (25 mg/kg, i.v.) effectively normalized an increased arterial blood pressure in irradiated animals. In conclusion, it appears that PCL due to its ability to normalize NO-dependent vascular tone control mechanisms might be worthwhile therapeutic approach in case of ionizing irradiation accident. These result support the concept that the depression of endothelium-dependent vascular responses after irradiation may be result of decreased NO bioavailability due to its conversion to less potent vasodilators during irradiation-induced oxidative attack.

Acetylcholine↗

PubMed1995

alpha-Toxin perfusion: a new method for selective impairment of endothelial function in isolated vessels or intact vascular beds.

We describe a method for selectively permeabilizing endothelial cells, using the membrane pore forming exoprotein Staphylococcus aureus alpha-toxin. Experiments were performed in rabbit central ear artery or its main side branch under isometric conditions, on the isolated perfused kidney, or in cannulated pressurized renal arteries. In presence of alpha-toxin, endothelial-dependent vasodilator responses elicited by acetylcholine or A23187 were abolished, whereas the sensitivity of smooth muscle cells to constrictors (norepinephrine, phenylephrine, or KCl) or dilators (sodium nitroprusside) was not affected. The results indicate that restricting the alpha-toxin to the luminal surface induces selective impairment of vascular endothelial function. This method of eliminating endothelium-dependent vasodilator responses may prove to be useful in the study of endothelial-smooth muscle interactions of isolated small arteries and intact vascular beds.

Acetylcholine↗