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PubMed2003

Tea consumption and cardiovascular disease: effects on endothelial function.

Epidemiological studies suggest that tea consumption is associated with reduced cardiovascular disease risk, but the mechanisms for these observations have remained uncertain. In recent years, it has become apparent that the endothelium plays a central role in the regulation of vascular homeostasis and that endothelial dysfunction contributes to the pathogenesis and clinical expression of cardiovascular disease. This article reviews the evidence that human tea consumption has a beneficial effect on the vascular endothelium and the clinical implications of these findings.

Cardiovascular Diseases↗

PubMed2005

Effects of adipocyte-derived cytokines on endothelial functions: implication of vascular disease.

Adipose tissue has recently emerged as an active endocrine organ that secretes a variety of metabolically important substances, collectively called adipocytokines or adipokines. In this review we summarize the effects of the adipokines leptin, adiponectin, and resistin on the vasculature and their potential role for pathogenesis of vascular disease. Leptin is associated with arterial wall thickness, decreased vessel distensibility, and elevated C reactive protein (CRP) levels. Leptin possesses procoagulant and antifibrinolytic properties, and it promotes thrombus and atheroma formation, probably through the leptin receptors by promoting vascular inflammation, proliferation, and calcification, and by increasing oxidative stress. Research for development of pharmacologic antagonism for the leptin receptor is currently under way. Adiponectin inhibits the expression of the adhesion molecules ICAM-1, VCAM-1, and P selectin. Therefore, it interferes with monocyte adherence to endothelial cells and their subsequent migration to the subendothelial space, one of the initial events in the development of atherosclerosis. Adiponectin also inhibits the transformation of macrophages to foam cells in vitro and decreases their phagocytic activity. Resistin, discovered in 2001, represents the newest of the adipokines and was named for its ability to promote insulin resistance. Resistin increases the expression of the adhesion molecules VCAM-1 and ICAM-1, up-regulates the monocyte chemoattractant chemokine-1, and promotes endothelial cell activation via ET-1 release. Although many aspects of its function need further clarification, it appears that resistin will add significantly to our knowledge of the pathophysiology of vascular disease and the metabolic syndrome.

Adiponectin↗

PubMed2005

Peripheral vascular endothelial function in essential hyperhidrosis.

BACKGROUND: Essential hyperhidrosis, a disorder of the eccrine sweat glands, is associated with sympathetic overactivity and the aim of the present study was to determine endothelium-dependent vasodilator function in patients with this condition. METHODS AND RESULTS: Using high-resolution ultrasound, the diameter of the brachial artery at rest and during reactive hyperemia (flow-mediated dilatation, %FMD endothelial-dependent stimulus to vasodilatation), as well as after sublingual administration of nitroglycerin (%NTG endothelium-independent vasodilatation) was measured in 18 subjects (mean age 27+/-5 years) with essential hyperhidrosis and 24 healthy control subjects (mean age 29+/-5 years). Baseline brachial artery diameter and FMD were comparable in both groups (BAD: 4.1+/-0.7 mm vs 4.3+/-0.5 mm (control), p = 0.8; FMD: 5.6+/-1.9% vs 6.7+/-2.2%, p=0.1). The time-averaged flow velocity during peak reactive hyperemia was similar in the 2 groups (75+/-11 cm/s vs 72+/-10 cm/s, p = 0.5), nor did NTG-induced dilatation in the patients with essential hyperhidrosis differ significantly from that in healthy control subjects (12.8+/-2.7% vs 14.0+/-3.6%, p = 0.3). CONCLUSION: These findings suggest that endothelium-dependent dilatation of large conduit arteries is preserved in essential hyperhidrosis and it seems to be a localized disorder of the eccrine sweat glands rather than a generalized disorder involving vascular endothelium.

Adult↗

PubMed2004

Ceramide-induced impairment of endothelial function is prevented by CuZn superoxide dismutase overexpression.

OBJECTIVE: Ceramide is an important intracellular second messenger that may also increase superoxide. The goal of this study was to determine whether overexpression of CuZn superoxide dismutase (SOD) protects against ceramide-induced increases in vascular superoxide and endothelial dysfunction. METHODS AND RESULTS: Carotid arteries from CuZnSOD-transgenic (CuZnSOD-Tg) and nontransgenic littermates were examined in vitro. Immunohistochemistry confirmed that CuZnSOD protein was greater in carotid artery from CuZnSOD-Tg compared with nontransgenic mice. Ceramide (N-acetyl-d-sphingosine; 1 and 10 micromol/L) produced concentration-dependent impairment (P<0.05) of vasorelaxation in response to the endothelium-dependent agonist acetylcholine (ACh) in nontransgenic mice. For example, 100 micromol/L ACh relaxed arteries from nontransgenic mice by 96+/-4% and 52+/-5% in the presence of vehicle and 10 micromol/L ceramide, respectively. In contrast, ceramide (1 or 10 micromol/L) had no effect (P>0.05) on responses of carotid artery to ACh in CuZnSOD-Tg mice. Ceramide had no effect on nitroprusside- or papaverine-induced relaxation in CuZnSOD-Tg or nontransgenic mice. Ceramide increased superoxide in arteries from nontransgenic vessels, and this effect was prevented by polyethyleneglycol-SOD (50 U/mL) or overexpression of CuZnSOD. CONCLUSIONS: These results suggest that ceramide-induced increases in superoxide impair endothelium-dependent relaxation, and that select overexpression of the CuZn isoform of SOD prevents ceramide-induced oxidative stress in vessels.

Animals↗

PubMed2004

Arginase inhibition restores arteriolar endothelial function in Dahl rats with salt-induced hypertension.

Vascular tissues express arginase that metabolizes L-arginine to L-ornithine and urea and thus reduces substrate availability for nitric oxide formation. Dahl salt-sensitive (Dahl-S) rats with salt-induced hypertension show endothelial dysfunction, including decreased vascular nitric oxide formation. This study tests the hypothesis that increased vascular arginase activity contributes to endothelial dysfunction in hypertensive Dahl-S rats. Male Dahl-S rats (5-6 wk) were placed on high (8%) or low (0.3%) NaCl diets for 4 wk. With respect to the low-salt group, mean arterial blood pressure was increased in the high-salt animals. Immunohistochemical stainings for arginase I and II were enhanced in arterioles isolated from high-salt Dahl-S rats. Experiments used isolated Krebs buffer-superfused first-order gracilis muscle arterioles with constant pressure (80 mmHg) and no luminal flow or constant midpoint but altered endpoint pressures to establish graded levels of luminal flow (0-50 microl/min). In high-salt arterioles, responses to an endothelium-dependent vasodilator acetylcholine (1 nmol/l to 3 micromol/l) and flow-induced dilation were decreased. Acute in vitro treatment with an inhibitor of arginase, 100 micromol/l (S)-(2-boronoethyl)-L-cystine, or the nitric oxide precursor, 1 mmol/l L-arginine, similarly enhanced acetylcholine and flow-induced maximal dilations and abolished the differences between high- and low-salt arterioles. These data show that arteriolar arginase expression is increased and that endothelium-dependent vasodilation is decreased in high-salt Dahl-S rats. Acute pretreatment with an arginase inhibitor or with L-arginine restores endothelium-dependent vasodilation and abolishes the differences between high- and low-salt groups. These results suggest that enhanced vascular arginase activity contributes to endothelial dysfunction in Dahl-S rats with salt-induced hypertension and identifies arginase as a potential therapeutic target to prevent endothelial dysfunction.

Animals↗

PubMed2004

Insulin resistance and endothelial function are improved after folate and vitamin B12 therapy in patients with metabolic syndrome: relationship between homocysteine levels and hyperinsulinemia.

OBJECTIVE: The purpose of this study was (a) to study whether a folate and vitamin B12 treatment, aimed at decreasing homocysteine levels, might ameliorate insulin resistance and endothelial dysfunction in patients with metabolic syndrome according to the National Cholesterol Education Program-Adult Treatment Panel-III criteria and (b) to evaluate whether, under these metabolic conditions, there is a relationship between hyperhomocysteinemia and insulin resistance. DESIGN AND METHODS: A double-blind, parallel, identical placebo-drug, randomized study was performed for 2 months in 50 patients. Patients were randomly allocated to two groups. In group 1, patients were treated with diet plus placebo for 2 months. In group 2, patients were treated with diet plus placebo for 1 month, followed by diet plus folic acid (5 mg/day) plus vitamin B12 (500 microg/day) for another month. RESULTS: In group 2, folate treatment significantly decreased homocysteine levels by 27.8% (12.2+/-1.2 vs 8.8+/-0.7 micromol/l; P<0.01). A significant decrement was observed for insulin levels (19.9+/-1.7 vs 14.8+/-1.6 microU/ml; P<0.01) accompanied by a 27% reduction in the homeostasis model assessment levels. A positive relationship was found between the decrement of homocysteine and insulin levels (r=0.60; P<0.002). In parallel, endothelial dysfunction significantly improved in the treated group, since post-ischemic maximal hyperemic vasodilation increased by 29.8% and cGMP by 13.6% while asymmetrical dimethylarginine levels decreased by 21.7%. On the contrary, in group 1 patients, treated with placebo, no changes were shown in any of the variables. CONCLUSIONS: Folate and vitamin B12 treatment improved insulin resistance and endothelial dysfunction, along with decreasing homocysteine levels, in patients with metabolic syndrome, suggesting that folic acid has several beneficial effects on cardiovascular disease risk factors.

Aged↗

PubMed2005

Effects of orthostatic stress on forearm endothelial function in normal subjects and in patients with hypertension, diabetes, or both diseases.

BACKGROUND: Sympathetically mediated vasoconstriction, to compensate for reduced venous return and cardiac output, characterizes the circulatory adaptation to head-up tilting (HUT). It has not been clarified whether this is coupled with a modulating endothelial vasorelaxation and whether diseases causing endothelial dysfunction, such as diabetes and hypertension, may impair this counterregulatory mechanism. METHODS: In patients with hypertension (group 1), diabetes (group 2), or both diseases (group 3) and in healthy control subjects (12 subjects per group) we investigated the brachial artery vasodilating response to the release of distal circulatory arrest (DCA) while they were supine and during 60 degrees HUT. RESULTS: The supine increase in lumen was smaller (P<.01) in groups 1 (+4.5%+/-1.5%), 2 (+4.8%+/-1.4%), and 3 (+3.9%+/-1.3%) than in the control group (+8.6%+/-1.6%). Vasorelaxation by nitroglycerin was similar in each population. During HUT, the lumen response to DCA was enhanced (P<.01 v supine) in control subjects (+15.4%+/-2.5%) and group 1 (+10.0+/-2.4%) and was reduced (P<.01 v supine) in groups 2 (+2.9%+/-0.5%) and 3 (+2.1%+/-0.4%), even though the hyperemic reaction to DCA was similar. The ratio of lumen changes to changes in flow (mm/mL/min x 1000) during reactive hyperemia to DCA increased (P<.01) with HUT, compared with that in the supine position, in control subjects (1.75v1.19) and group 1 (1.61v0.95), and decreased (P<.01) in groups 2 (0.62v0.87) and 3 (0.48v0.77). CONCLUSIONS: The HUT posture is characterized by an increased endothelium-dependent, flow-mediated vasodilation as a possible modulator of the neural vasoconstriction. This effect is persistent but blunted in hypertension and is abolished in diabetes, either alone or in association with high BP. Thus, vasoconstrictor factors could remain unmodulated during an event such as orthostasis, making the risk posed by these disorders more critical.

Blood Pressure↗

PubMed1996

Modulation of endothelial function: strategy for long-term cardiovascular protection.

PROPERTIES OF THE ENDOTHELIUM: The endothelium lines all vessels of the body and is the most important communication structure between flowing blood on one hand and the vessel wall, composed of smooth muscle cells and matrix proteins, on the other. Endothelial cells release factors that affect the differentiation and growth of vascular smooth muscle cells; dedifferentiation and subsequent proliferation of vascular smooth muscle cells are important early mechanisms in the pathogenesis of chronic vascular disease. CALCIUM ANTAGONISTS AND THE ENDOTHELIUM: Calcium antagonists primarily affect the cellular interactions of endothelial cells, smooth muscle cells, monocytes and thrombocytes, which are important in the early phases of the development of atherosclerosis. The protective effect of calcium antagonists on the vascular system appears to be low at later stages, which include increased matrix formation and central necrosis of atherosclerotic plaques. CONCLUSION: Present evidence indicates that calcium antagonists may be useful prophylactic agents at an early stage in the development of atherosclerotic vascular changes.

Animals↗

PubMed2005

[Endothelial function and ischemic heart disease].

The original hypothesis of the development of human atherosclerosis and ischemic heart disease called "response-to-injury" suggested the loss of integrity of the endothelium as the first step of the process. The recent version of this hypothesis emphasizes the term of endothelial dysfunction, that can be triggered by any of the well known cardiovascular risk factors. The atherosclerotic process, starting with endothelial dysfunction is a slow grade inflammatory process, promoting the oxidation of the low density lipoprotein molecules, activation of cell adhesion molecules as well as various ligands and cytokines, and activating immunological processes resulting in the development of unstable atherosclerotic plaque, followed by plaque rupture and formation of atherothrombotic lesions. Among the laboratory methods used for the detection of endothelial dysfunction, the flow mediated vasodilation (FMD) is increasingly known. A novel method is the laser Doppler flowmetry, still adapted to routine clinical tests. Clinical experiments are currently running with the coronarographic evaluation of intravascular flow velocity (slow coronary flow phenomenon), and also with the isolation and clinical evaluation of the circulating endothelial cells in patients with ischemic heart disease.

Arteritis↗

PubMed2005

Effect of rosiglitazone on insulin resistance, C-reactive protein and endothelial function in non-obese young women with polycystic ovary syndrome.

OBJECTIVE: Women with polycystic ovary syndrome (PCOS) exhibit elevated levels of serum C-reactive protein (CRP) and impaired endothelium dysfunction which are directly correlated with insulin resistance. Because rosiglitazone improves insulin sensitivity, we tested whether rosiglitazone treatment ameliorates high-sensitivity (hs)CRP levels and endothelial dysfunction in these patients. DESIGN: Thirty-one women with PCOS were recruited (mean age, 24.7+/-3.9 (s.e.) years; mean body mass index (BMI), 25.6+/-3.2 kg/m2). All women were treated with 4 mg rosiglitazone daily for 12 months. METHODS: Serum levels of testosterone, LH, FSH, sex hormone-binding globulin (SHBG), insulin and hsCRP were measured. The BMI, hirsutism scores and insulin sensitivity indices were calculated before and after treatment. Arterial endothelium and smooth muscle function was measured by examining brachial artery responses to endothelium-dependent and endothelium-independent stimuli before and after treatment. RESULTS: After treatment with rosigitazone there were significant decreases in serum testosterone (91.2+/-37.5 vs 56.1+/-21.8 ng/dl; P < 0.01) and fasting insulin concentrations (12.5+/-7.6 vs 8.75+/-4.03 microU/ml; P = 0.015). Insulin resistance indices were significantly improved after rosiglitazone treatment (P < 0.05). There were no significant changes in BMI, waist circumference, serum total cholesterol, low-density lipoprotein (LDL)-cholesterol, FSH and LH levels. Hirsutism score was decreased significantly after treatment (10.8+/-1.8 vs 7.6+/-1.7; P < 0.05). Twenty-four of the women reverted to regular menstrual cycles. Levels of SHBG increased significantly after treatment (28.7+/-8.7 vs 48.4+/-11.2 nmol/l; P < 0.01). Serum hsCRP levels were decreased significantly after rosiglitazone treatment (0.25+/-0.1 vs 0.09+/-0.02 mg/dl; P = 0.006). There was also significant improvement in endothelium-dependent vascular responses after rosiglitazone treatment (9.9+/-3.9 vs 16.4+/-5.1%; P < 0.01). CONCLUSIONS: We conclude that rosiglitazone treatment improves insulin sensitivity in women with PCOS. It also decreases androgen production without significant weight gain. More importantly, it has beneficial effects on endothelial dysfunction and low-grade chronic inflammation in normal weight young women with PCOS.

Adult↗

PubMed2005

Effects of resveratrol on vascular tone and endothelial function of human saphenous vein and internal mammary artery.

BACKGROUND: The polyphenolic compound resveratrol presented in red wine has potent cardiovascular effect in animal. Here, we investigated the ability of resveratrol to relax human coronary bypass grafts, saphenous vein and internal mammary artery and also its effect on their endothelial reactivity. METHODS: Vascular rings were obtained from 38 male patients undergoing coronary artery bypass operation. The relaxant effects of resveratrol (10-70 microM) and acetylcholine (10(-8)-10(-4) M) were examined on precontracted saphenous vein and internal mammary artery rings. RESULTS: Resveratrol, at concentration of 70 microM caused relaxations of 34.2+/-5.7% in saphenous vein and 35.2+/-5.4% in internal mammary artery. Endothelium removal and l-NOARG (nitric oxide synthase inhibitor, 10(-4) M) pretreatment almost completely inhibited the relaxation to resveratrol in internal mammary artery but partially in saphenous vein rings. Indomethacin (cyclooxygenase inhibitor, 10(-5) M) slightly, but not significantly enhanced the relaxation to resveratrol in both vessels. The endothelium-dependent relaxations to acetylcholine were significantly improved in the presence of resveratrol of 20 microM in both grafts (E(max): 33.8+/-3.7% versus 46.8+/-4% in saphenous vein n=9; p<0.05; 54. 4+/-5.3% versus 69.3+/-5.4% in internal mammary artery, n=8, p<0.05). The relaxations to acetylcholine were fully eliminated by combination of resveratrol with l-NOARG (10(-4) M) in both vessels. CONCLUSIONS: Resveratrol produced mainly endothelium-dependent and nitric oxide-mediated vasodilation in human internal mammary artery but partially in saphenous vein rings and improved their endothelial reactivity. This may have a therapeutic potential in cardiovascular diseases.

Acetylcholine↗

PubMedDate not supplied

Removal of endothelial function in coronary resistance vessels by saponin.

Studies of the role of the endothelium in coronary resistance vessels are limited to investigations of endothelium-derived relaxing factor mediated effects using various blocking agents. Endothelium removal as an alternative approach, is restricted to larger epicardial vessels. This study demonstrates the effect of endothelial damage by saponin on coronary resistance vessels remaining intact within the heart. In an isolated perfused guinea pig heart a saponin-containing solution (50 micrograms/ml) was infused over 2 min to damage specifically the endothelium. Increases of coronary flow in response to carbachol, histamine, and serotonin were completely blocked and reversed to decreases. Angiotensin-I-induced vasoconstriction was attenuated, whereas angiotensin-II-induced vasoconstriction remained unchanged. Vasodilatory response to sodium-nitroprusside was not attenuated by saponin-treatment. In contrast inhibition of endothelium derived relaxing factor by gossypol inhibited carbachol-induced vasodilation but did not result in vasoconstriction. Electron microscopic examination ensured that while the endothelium was destroyed by saponin-treatment the vascular smooth muscle was left intact. Our data indicate a regulating influence of the vascular endothelium on coronary resistance vessels which can be totally eliminated by saponin-treatment.

Angiotensin II↗

PubMed1989

[Endothelial function in contact lens-induced deep corneal opacities].

Deep stromal and preendothelial corneal opacities have been described to be a problem of growing importance in contact lens wearers, above all in those with a more than ten-year-old history of contact lens wearing. In the present study the corneal endothelial permeability of 21 patients with a more than ten-year-old history of contact lens (HEMA 38%) wearing has been determined and compared with that of an age-matched group of 8 healthy individuals without ocular disease. The corneal endothelial permeability has been measured by a computerized automated fluorophotometer (Coherent Radiation Fluorotron Master) after topical application of a Na-fluorescein solution according to the method described by Jones and Maurice. The corneal endothelial permeability of contact lens wearers with deep corneal opacities has been found to be significantly (p = 0.05) increased when compared with contact lens wearers without corneal opacities. Contact lens wearers without corneal opacities showed no significant increase of their endothelial permeability in comparison to the control group.

Cell Membrane Permeability↗

PubMed2001

Abnormal haemorheology, endothelial function and thrombogenesis in relation to hypertension in acute (ictus < 12 h) stroke patients: the West Birmingham Stroke Project.

While the blood vessels are exposed to high pressures in hypertension, the main complications of hypertension (stroke and myocardial infarction) are paradoxically thrombotic rather than haemorrhagic. To investigate abnormalities of haemorheology (plasma viscosity, fibrinogen), endothelial dysfunction (von Willebrand factor), platelet activation (soluble P-selectin) and thrombogenesis (plasminogen activator inhibitor and fibrin D-dimer) in stroke and the effects of concurrent hypertension, we studied 86 consecutive patients (58 male, 28 female) aged < 75 years (mean age +/- SD, 64.2 +/- 9.2 years) with acute stroke (ictus < 12 h). Baseline blood tests on admission were compared with 46 'hospital controls' (patients with uncomplicated essential hypertension; mean age +/- SD, 65.9 +/- 3.8 years) and 24 healthy normotensive controls (mean age +/- SD, 65 +/- 14.0 years). Further comparisons were made between stroke patients with hypertension (systolic blood pressure > 160 mmHg and/or diastolic > 90 mmHg) on admission and those without hypertension. Mean plasma viscosity (one-way analysis of variance, P = 0.026) and fibrinogen levels (P = 0.016) were significantly higher in stroke patients and hospital controls, when compared with healthy controls. The von Willebrand factor, plasminogen activator inhibitor soluble P-selectin and fibrin D-dimer levels were highest in the acute stroke patients, intermediate in hospital controls and lowest in healthy controls (all P < or = 0.001). There were no significant differences in measured indices of haemorheology, endothelial dysfunction and thrombogenesis between the three stroke pathological subtypes (ischaemic/thrombotic, haemorrhagic or transient ischaemic attack). There were also no significant differences in the measured parameters for stroke patients with or without systolic blood pressure > 160 mmHg or diastolic blood pressures > 90 mmHg using clinical (manual) readings or mean daytime or night-time ambulatory blood pressure monitoring recordings. There were no statistically significant differences between the measured parameters on admission and at 3 months follow-up in 26 patients (all P = not significant). Plasma viscosity was significantly correlated with mean daytime systolic blood pressure (r = 0.314, P = 0.021) and mean night-time systolic blood pressure (r = 0.309, P = 0.025). This study of hypertension and haemostasis in acute stroke has demonstrated clear abnormalities of haemorheology, endothelial dysfunction, platelet activation and thrombogenesis, which do not appear to be affected by the height of the blood pressure or the presence of hypertension. This is despite the known hypercoagulable state found in hypertension and the relationship of haemostatic abnormalities to vascular complications.

Aged↗

PubMed1995

Aging and endothelial function in normotensive subjects and patients with essential hypertension.

BACKGROUND: Experimental data from normotensive and hypertensive animals indicate that aging is associated with impaired endothelium-dependent relaxations to acetylcholine, and this possibility appears to be confirmed in the human coronary artery. In the present study, we evaluated the effect of age on endothelial responsiveness in the forearm vessels of either normotensive control subjects or essential hypertensive patients. METHODS AND RESULTS: Within the normotensive or hypertensive group (n = 53 and n = 57, respectively), subjects were selected with similar blood pressure, plasma cholesterol, and glucose values, and hypercholesterolemic subjects, diabetics, and smokers were excluded. We evaluated forearm blood flow (by strain-gauge plethysmography) modifications induced by intrabrachial acetylcholine (0.15, 0.45, 1.5, 4.5, and 15 micrograms/100 mL per minute), an endothelium-dependent vasodilator, and sodium nitroprusside (1, 2, and 4 micrograms/100 mL per minute), an endothelium-independent vasodilator. Acetylcholine caused a dose-dependent vasodilation that was significantly (P < .01) lower in essential hypertensive patients than in normotensive control subjects. However, a significant negative correlation was observed between acetylcholine-induced vasodilation and patient age in both normotensive (r = -.86, P < .001) and hypertensive (r = -.85, P < .001) patients. In contrast, vasodilation to sodium nitroprusside was similar in normotensive control subjects and essential hypertensive patients with a poorer inverse correlation with patient age (normotensive control subjects, r = -.37; hypertensive patients, r = -.36) compared with acetylcholine. CONCLUSIONS: The present data indicate that there is a blunted response to acetylcholine with advancing age in both normotensive control subjects and essential hypertensive patients, suggesting that aging is associated with reduced endothelium-dependent vasodilation in humans.

Acetylcholine↗

PubMed1998

Transcardiac 5-hydroxytryptamine release and impaired coronary endothelial function in patients with vasospastic angina.

1. The present study was designed to test the hypotheses whether platelet degranulation across the coronary bed is detectable during non-ischaemic periods in patients with vasospastic angina (VSA) and whether the exogenous nitric oxide (NO) donor nitroglycerin (GTN) is able to modify platelet degranulation, reflecting an impaired endothelial production of NO. 2. We studied 13 patients with VSA and 10 controls. The time course of coronary sinus (CS) plasma 5-hydroxytryptamine (5-HT) levels was evaluated every 4 h before and after intravenous infusion of GTN over a period of 40 h. Coronary sinus plasma 5-HT levels were significantly higher at any measured time point in patients with VSA compared with control and were significantly decreased in patients with VSA following treatment with GTN, but not in controls. Femoral artery plasma 5-HT levels remained almost constant throughout the study. The ratio of CS:aorta 6-keto-prostaglandin F1 alpha was significantly and inversely correlated with the transcardiac plasma 5-HT difference only in patients with VSA (r = -0.68; P < 0.02; n = 13). 3. The time course of CS 5-HT levels confirmed significant platelet degranulation across the coronary bed supplied by the spasming artery in patients with VSA and this was modified by GTN. The present data suggest that platelet degranulation occurs during non-ischaemic periods in patients with VSA and that prostacyclin biosynthesis may be a compensatory response to an impaired endothelial release of NO, limiting the degree of the effects of platelet degranulation.

6-Ketoprostaglandin F1 alpha↗

PubMed1992

Endothelial function in thrombosis and thrombolysis.

The localization of tissue factor (TF) in atherosclerotic plaques of human aortas was immunohistochemically examined using rabbit anti-IgG against recombinant TF, which was expressed in E. coli. TF, the initiator of the extrinsic coagulation pathway, was ubiquitously present in atherosclerotic intima, and was expressed mainly by macrophages, but not by endothelial cells. It has been suggested that some macrophages in atherosclerotic intima co-express both molecules of TF and platelet-derived growth factor-B chain. We have developed a morphometrically quantitative in vitro assay for angiogenesis, using endothelial cultures on collagen gel incorporating plasminogen. With this method, we have obtained findings suggesting that plasminogen and plasminogen activators (PAs), especially urokinase-type PA (uPA) derived from endothelial cells, enhance angiogenic activity, probably by increasing endothelial migration. uPA was immunohistochemically observed to be primarily cell-associated on the focal contract areas, probably via its receptors on endothelial cells. These findings may support the hypothesis that the activation and regulation of the pericellular fibrinolysis system is closely related to angiogenesis.

Animals↗

PubMed2003

Possible mechanisms underlying pregnancy-induced changes in uterine artery endothelial function.

The last 10 years has seen a dramatic increase in our understanding of the mechanisms underlying the pregnancy-specific adaptation in cardiovascular function in general and the dramatic changes that occur in uterine artery endothelium in particular to support the growing fetus. The importance of these changes is clear from a number of studies linking restriction of uterine blood flow (UBF) and/or endothelial dysfunction and clinical conditions such as intrauterine growth retardation (IUGR) and/or preeclampsia in both humans and animal models; these topics are covered only briefly here. The recent developments that prompts this review are twofold. The first is advances in an understanding of the cell signaling processes that regulate endothelial nitric oxide synthase (eNOS) in particular (Govers R and Rabelink TJ. Am J Physiol Renal Physiol 280: F193-F206, 2001). The second is the emerging picture that uterine artery (UA) endothelial cell production of nitric oxide (NO) as well as prostacyclin (PGI2) may be as much a consequence of cellular reprogramming at the level of cell signaling as due to tonic stimuli inducing changes in the level of expression of eNOS or the enzymes of the PGI2 biosynthetic pathway (cPLA2, COX-1, PGIS). In reviewing just how we came to this conclusion and outlining the implications of such a finding, we draw mostly on data from ovine or human studies, with reference to other species only where directly relevant.

Animals↗