SEARCH · PubMed Health

Results for “Endothelial function”

Explore indexed PubMed citations for clinical trials, systematic reviews and public health research. Read source abstracts and follow each citation to its original PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 1,405 records · Page 78Linked to original sources

PubMed2001

Vasopeptidase inhibition and endothelial function in hypertension.

Vasopeptidase inhibitors are a new class of drugs capable of inhibiting both angiotensin-converting enzyme and neutral endopeptidase 24.11. This involves simultaneous inhibition with a single molecule of two key enzymes, ACE and NEP, which are both involved in the regulation of cardiovascular homeostasis in many ways. This includes metabolism of several vasoactive peptides and their clearance from the circulation, therefore contributing to neurohumoral modulation, which might have therapeutic advantages in the prevention of endothelial dysfunction in hypertension.

Angiotensin-Converting Enzyme Inhibitors↗

PubMed1992

Endothelial function in normal and pre-eclamptic pregnancy: a hypothesis.

Pre-eclampsia is the most common medical complication of pregnancy. Immunologic maladaptation has been suggested to play a role in the etiology of pre-eclampsia. The putative misalliance of fetal trophoblast with maternal tissue in the uteroplacental vascular bed may give rise to an increase in oxygen free radicals. Oxygen free radicals and lipid peroxides might form the link between the hypothetical immunologic maladaptation and the endothelial cell damage known to occur in pre-eclampsia. Recent studies have demonstrated the existence of increased oxygen free radical production in pre-eclampsia. Oxygen free radicals and lipid peroxides decrease vascular prostacyclin and EDRF release and increase thromboxane A2 and endothelin release. The hypothesis is put forward that in pre-eclampsia a proposed immunologic maladaptation causes an increase in oxygen free radicals by decidual lymphoid cells. A decrease in vasodilatory autocoids, prostacyclin and EDRF may result from the endothelial cell damage induced by oxygen free radicals. Uteroplacental prostacyclin production might be essential as escape mechanism. The adequacy as escape mechanism seems to determine the final clinical outcome.

Blood Platelets↗

PubMed1998

The role of endothelial function on the foot. Microcirculation and wound healing in patients with diabetes.

Wound healing is defective in patients with diabetes, which may be attributed to many factors. Our data indicate that impairment of the microcirculation is a major factor. Although the exact causes of microvascular impairment are not known, dysfunction of the endothelium has emerged over the last decade as the prominent abnormality related to vascular disease in diabetes. Further studies are required to clarify the causes of endothelial dysfunction and identify potential therapeutic interventions in the future.

Diabetic Foot↗

PubMed2005

Angiotensin II regulation of ovine fetoplacental artery endothelial functions: interactions with nitric oxide.

During normal pregnancy, elevated angiotensin II (Ang II) concentrations in the maternal and fetal circulations are associated with dramatic increases in placental angiogenesis and blood flow. Much is known about a local renin-angiotensin system within the uteroplacental vasculature. However, the roles of Ang II in regulating fetoplacental vascular functions are less well defined. In the fetal placenta, the overall in vivo vasoconstrictor responses of the blood vessels to Ang II infusion is thought to be less than that in its maternal counterpart, even though infused Ang II induces vasoconstriction. Recent data from our laboratories suggest that Ang II stimulates cell proliferation and increases endothelial nitric oxide synthase (eNOS) and production of nitric oxide (NO) in ovine fetoplacental artery endothelial cells. These data imply that elevations of the known vasoconstrictor Ang II in the fetal circulation may indeed play a role in the marked increases in fetoplacental angiogenesis and that Ang II-elevated endothelial NO production may partly attenuate Ang II-induced vasoconstriction on vascular smooth muscle. Together with both of these processes, the high levels of Ang II in the fetal circulation may serve to modulate overall fetoplacental vascular resistance. In this article, we review currently available data on the expression of Ang II receptors in the ovine fetal placenta with particular emphasis on the effects of Ang II on ovine fetoplacental endothelium. The potential cellular mechanisms underlying the regulation of Ang II on endothelial growth and vasodilator production are discussed.

Animals↗

PubMed2002

[Selected problems of endothelial functions. II. The role of the selectines in the damage of vascular endothelium].

Studies in the recent years have provided numerous evidence of the inflammatory and immunological character of atherosclerosis. In the early stages of the adhesion of leucocytes and platelets to the blood vessel wall, and also in occurring intercellular interactions leading to creating the atherosclerotic lamina, the adhesive molecules from the selectine family ply the crucial role. Their expression, mainly selectines L, P and E on the endothelial surface and on the smooth muscles of the vessels, undergoes a distinct intensification under the influence of hypoxia. The begun cascade of molecular changes with the contribution of selectines leads inevitably to the development of atherosclerotic changes. The neutrophile and lymphocyte fixed to the endothelium show ability to its damage, both as a result of immediate response [release of free oxygen radicals, enzymes and cytoxic substances] and as a result of indirect action [release of cytocines which change the biological property of the endothelium--the so called endothelial activation]. In this work the role of diabetes and hypertension in the intensification of those processes has been noticed.

Arteriosclerosis↗

PubMed2000

Time and dose effect of transdermal nicotine on endothelial function.

Nicotine patches are available as an over-the-counter medication for aid in smoking cessation. This study was designed to determine how nicotine patch therapy over time and dose ranges used in smoking cessation programs in humans affects endothelium-dependent relaxations. Dogs were treated with nicotine patches (11, 22, or 44 mg/day) for 2 and 5 wk. Circulating nicotine and oxidized products of nitric oxide (NOx) were measured. Coronary arteries were prepared for measurement of isometric force and aortic endothelial cells were prepared for measurement of mRNA or NO synthase (NOS) activity. Circulating nicotine increased with increasing concentrations of nicotine patches. After 5 wk of treatment with 22 mg/day patches, circulating NOx was reduced but NOS activity was increased. NOS mRNA was similar among groups. Only after 5 wk of treatment with 22 mg/day patches were endothelium-dependent relaxations reduced to alpha(2)-adrenergic agonists, ADP, and the calcium ionophore A-23187. These results suggest a time and biphasic dose effect of nicotine treatment on endothelium-dependent responses that may be related to bioavailability of NO. This complex relationship of duration and dose of nicotine treatment may explain, in part, discrepancies in effects of nicotine on endothelium-dependent responses.

Adenosine Diphosphate↗

PubMed1991

Preservation of endothelial function by ramipril in rabbits on a long-term atherogenic diet.

Hypertension and hypercholesterolemia predispose to atherosclerosis. Ramipril, known to lower blood pressure, was used to study the effect of converting-enzyme inhibition on impairment of endothelium-derived relaxation and changes in basal cGMP content in rabbits fed an atherogenic diet (0.25% cholesterol). The generation of cGMP in the presence of bradykinin and ramiprilat was studied in vitro in aortic segments from normal untreated rabbits as well as in bovine endothelial cells. The ability to relax in response to acetylcholine was almost abolished in aortic segments from the vehicle-treated rabbits fed the atherogenic diet for 4 months. The basal cGMP content was substantially reduced. Aortic segments from rabbits concomitantly treated with ramipril (0.3 and 3.0 mg/kg/day) for 3 months showed well-preserved relaxation and matching basal cGMP content compared to normal controls. The relaxation was not significantly greater in aortic segments from ramipril-treated rabbits fed the standard diet, but the cGMP content was more than doubled. In vitro studies in aortic segments and in endothelial cells showed that both the ramiprilat and bradykinin concentrations dependently stimulated cGMP formation, which serves as a biochemical marker of nitric oxide or EDRF release. Thus, the observed endothelial protection against hypercholesterolemia by ramipril may be the result of continuously increased cGMP formation due to preserved EDRF release. This is presumably produced by enhanced bradykinin activity through inhibition of degradation by converting-enzyme inhibition with ramipril.

Angiotensin-Converting Enzyme Inhibitors↗

PubMed2000

Impaired endothelial function in transgenic mice expressing both human renin and human angiotensinogen.

BACKGROUND AND PURPOSE: Chronic hypertension is a risk factor for carotid vascular disease and stroke. Mechanisms that account for alterations in carotid and cerebral vascular function during hypertension are poorly defined and based almost exclusively on studies in the spontaneously hypertensive rat, a model in which hypertension has an unknown etiology and in which the genetic background is dissimilar to the most commonly used normotensive control, the Wistar-Kyoto rat. METHODS: In this study we examined vascular function in a defined model of hypertension, double transgenic mice that overexpress both human renin (R+) and human angiotensinogen (A+). We studied vessels in vitro from R+/A+ mice as well as nontransgenic (R-/A-) and single transgenic (R-/A+ or R+/A-) littermate controls. RESULTS: After submaximal precontraction with U46619 or prostaglandin F(2alpha), acetylcholine, which produces relaxation mediated by endothelial nitric oxide synthase, produced marked relaxation of carotid arteries in control mice but was impaired in R+/A+ mice. For example, 1 micromol/L acetylcholine relaxed the carotid artery by 79+/-4% versus 44+/-7% (P<0.01) in control and R+/A+ mice, respectively. Impaired responses to acetylcholine in R+/A+ mice could be restored toward normal with indomethacin (10 micromol/L). In contrast, relaxation of the carotid artery in response to nitroprusside and papaverine was similar in R+/A+ mice and control mice. CONCLUSIONS: These findings indicate that acetylcholine-induced relaxation of carotid artery is impaired selectively in mice made hypertensive by expression of human renin and human angiotensinogen. The mechanism of this impairment may involve production of a cyclooxygenase-derived contracting factor.

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

PubMed2003

Pulmonary preservation studies: effects on endothelial function and pulmonary adenine nucleotides.

BACKGROUND: Lung transplantation is an effective therapy plagued by a high incidence of early graft dysfunction, in part because of reperfusion injury. The optimal preservation solution for lung transplantation is unknown. We performed experiments using an isolated perfused rat lung model to test the effect of lung preservation with three solutions commonly used in clinical practice. METHODS: Lungs were retrieved from Sprague-Dawley rats and flushed with one of three solutions: modified Euro-Collins (MEC), University of Wisconsin (UW), or low potassium dextran and glucose (LPDG), then stored cold for varying periods before reperfusion with Earle's balanced salt solution using the isolated perfused rat lung model. Outcome measures were capillary filtration coefficient (Kfc), wet-to-dry weight ratio, and lung tissue levels of adenine nucleotides and cyclic AMP. RESULTS: All lungs functioned well after 4 hr of storage. By 6 hr, UW-flushed lungs had a lower Kfc than LPDG-flushed lungs. After 8 hr of storage, only UW-flushed lungs had a measurable Kfc. Adenine nucleotide levels were higher in UW-flushed lungs after prolonged storage. Cyclic AMP levels correlated with Kfc in all groups. CONCLUSIONS: Early changes in endothelial permeability seemed to be better attenuated in lungs flushed with UW compared with LPDG or MEC; this was associated with higher amounts of adenine nucleotides. MEC-flushed lungs failed earlier than LPDG-flushed or UW-flushed lungs. The content of the solution may be more important for lung preservation than whether the ionic composition is intracellular or extracellular.

Adenine Nucleotides↗

PubMed1994

Vascular renin-angiotensin-system, endothelial function and atherosclerosis?

Clinical observations demonstrate an enhanced risk for myocardial infarction in patients with sustained activation of the local and/or systemic renin-angiotensin system, such as a high renin-sodium profile or a heritably enhanced expression of angiotensin converting enzyme. Chronic renin-angiotensin system blockade by angiotensin converting enzyme inhibition in patients with moderate heart failure reduces the rate of myocardial infarction and reinfarction. Preliminary experimental evidence suggests that these clinical observations may be partially explained by a proatherogenic effect of an activated renin-angiotensin system, which can downregulate the endothelial releasability of nitric oxide. Nitric oxide exerts many potentially antiatherogenic effects on endothelium, platelets and low density lipoproteins and indirectly on monocytes and leukocytes. Hypertension-induced chronic distension of elastic arteries upregulates the local renin-angiotensin system in these arteries and thereby downregulates nitric oxide releasability. Enhanced local synthesis of the trophic factor angiotensin-II and reduced releasability of the antitrophic factor nitric oxide appear to cooperate in the trophic adaptation of the distended vessel wall to the enhanced load, but with the disadvantage of enhanced susceptibility for atheroma development due to reduced releasability of nitric oxide. Chronic blockade of the renin angiotensin system by angiotensin converting enzyme inhibitors or by angiotensin receptor type-1 antagonists normalizes a reduced endothelial releasability of nitric oxide in several models, partially by a bradykinin-dependent mechanism. This endothelial protection proved to attenuate the progression of atherosclerosis in experimental models. The antiatherogenic potential of renin angiotensin system blockade in humans is presently under study.

Angiotensin-Converting Enzyme Inhibitors↗

PubMed1976

Effects of mechanical agitation on endothelial function of preserved corneas.

Corneas from adult albino New Zealand rabbits were stored in either MK medium or moist chambers at 4 degrees C. for 18 to 24 hours. During that time, half the corneas from each group were agitated for 8 hours to simulate the motion that might occur during long-distance shipment. The corneas were then placed in specular microscopes and perfused for 4 hours with a modified Krebs-Ringer solution at 34 degrees C. Serial measurements of corneal thickness made during temperature reversal showed that agitation had no effect on endothelial viability of corneas stored in either solution. Electron microscopy of selected corneas confirmed this finding.

Animals↗

PubMed1994

Different influence of superoxide anions and hydrogen peroxide on endothelial function of isolated cat cerebral and pulmonary arteries.

1. Exogenous superoxide dismutase (SOD) or catalase did not modify isolated cat middle cerebral arterial basal tone. Catalase but not SOD reduced ACh relaxation. 2. H2O2 induced endothelium-independent relaxation which was abolished by catalase. 3. 3-Amino-1,2,4-triazole (AT) evoked endothelium-dependent contractions and diminished ACh relaxation. 4. Diethyldithio carbamic acid (DETC) induced endothelium-independent relaxation and did not modify ACh vasodilatation. 5. ACh relaxation of cat isolated pulmonary arteries was unaffected by SOD, catalase or AT, and diminished by DETC. 6. Endothelial catalase but neither SOD nor superoxide anions is involved in EDRF cerebral vasodilatation and H2O2 participates in ACh relaxation. In pulmonary arteries, only endothelial SOD activity plays a role.

Acetylcholine↗

PubMed2004

Alterations in vascular endothelial function in the aorta and mesenteric artery in type II diabetic rats.

We used the partial protection exerted by suitable dosages of nicotinamide against the beta-cytotoxic effect of streptozotocin (STZ) to create an experimental diabetic syndrome in adult rats that appears closer to type II diabetes mellitus than other available animal models. The dosage of 230 mg/kg of nicotinamide given intraperitoneally 15 min before STZ administration (65 mg/kg i.v.) yielded animals with hyperglycemia (187.8 +/- 17.8 vs. 103.8 +/- 2.8 mg/dL in controls; P < 0.001) and preservation of plasma insulin levels. This study assessed the relationship between endothelial dysfunction and agonist-induced contractile responses in such rats. In the thoracic aorta, the acetylcholine (ACh) induced relaxation was significantly reduced and the noradrenaline (NA) induced contractile response was significantly increased in diabetic rats compared with age-matched control rats. In the superior mesenteric artery, the ACh-induced relaxation was similar in magnitude between diabetic and age-matched control rats; however, the ACh-induced endothelium-derived hyperpolarizing factor (EDHF) type relaxation was significantly weaker in diabetic rats than in the controls. The phenylephrine (PE) induced contractile response was not different between the two groups. The plasma concentration of NOx (NO2- + NO3-) was significantly lower in diabetic rats than in control rats. We conclude that vasomotor activities in conduit arteries are impaired in this type II diabetes model.

Acetylcholine↗

PubMed2003

Enhancement of endothelial function by pregnancy: inadequate response in women with type 1 diabetes.

OBJECTIVE: Pregnant women with type 1 diabetes have a substantially increased risk of vascular complications. Our aim was to study vascular function and metabolic and inflammatory risk factors during the antenatal and postpartum periods in women with type 1 diabetes compared with healthy control subjects. RESEARCH DESIGN AND METHODS: A total of 15 women with diabetes and 30 control subjects were recruited in the third trimester of pregnancy. Of these women, 9 case subjects and 16 control subjects were reinvestigated in the postnatal period. Blood samples were collected and microvascular skin perfusion was assessed in vivo using laser Doppler imaging and iontophoretic administration of endothelial-dependent (acetylcholine [ACH]) and endothelial-independent (sodium nitroprusside [SNP]) vasodilators. RESULTS: Microvascular responses in both control subjects (ACH, P = 0.018; SNP, P = 0.01) and diabetic women (ACH, P = 0.029; SNP, P = 0.105) were better during pregnancy than in the postnatal period, although responses in women with diabetes were significantly inferior to those in control subjects during both periods (all P < 0.001, two-way ANOVA). This dysfunction existed despite similar lipoprotein profiles. The difference in vascular responsivity between case and control subjects was significantly attenuated by adjustment for differences in HbA(1c) but not C-reactive protein concentrations in the two groups. CONCLUSIONS: Pregnancy enhances microvascular function, but in women with diabetes, such improvements are insufficient to attain responses seen in healthy nonpregnant women. This suggests a persistent vascular defect in young women with type 1 diabetes that may contribute to adverse pregnancy outcome. Our data suggest a role for the chronic effects of hyperglycemia in the impaired vascular responsiveness in such women.

Acetylcholine↗

PubMed1996

Lipids and endothelial function: effects of lipid-lowering and other therapeutic interventions.

Coronary arteries are regulated by neuronal mechanisms, hormones and paracrine mediators. The importance of endothelium-dependent mechanisms has recently been recognized. The endothelium responds to mechanical and chemical signals from the blood by releasing mediators that modulate vascular tone and structure, platelet function, coagulation and monocyte adhesion. Important relaxing factors are nitric oxide, prostacyclin and a putative hyperpolarizing factor. Nitric oxide also inhibits smooth muscle proliferation and, together with prostacyclin, platelet function. Bradykinin-induced nitric oxide production is reduced by angiotensin-converting enzyme. Endothelin-1, thromboxane A2 and prostaglandin H2 are contracting factors. Thromboxane A2 and prostaglandin H2 activate platelets, while endothelin has no direct platelet effects, but causes smooth muscle proliferation. In hypercholestermia, endothelium-dependent relaxation is impaired and contraction as well as adhesion of monocytes and platelets enhanced. Pharmacological correction of hyperlipidemia by statins also improves or normalizes endothelial dysfunction in patients. Angiotensin-converting enzyme inhibitors have similar effects.

Angiotensin-Converting Enzyme Inhibitors↗

PubMed1993

[EDRF/NO and endothelial functions].

Our appreciation of the vascular endothelium has changed considerably over the last decade. This organ, finally recognized as such, participates actively in vasomotor regulation and haemostasis. It secretes several relaxing and contracting factors which act locally to determine resting vascular tone. One of the relaxing factors, EDRF/NO plays an important physiological role as it contributes to the rapid adaptation of blood flow to various pharmacological and mechanical stimuli, thereby ensuring maintenance of adequate tissue perfusion. Nitric oxide (NO) is an ubiquitous factor which was crowned "molecule of the year 1992" by the scientific review Science. Its effects extend well beyond those on the cardiovascular system. Endothelial dysfunction is observed in many pathological states such as atherosclerosis, reperfusion injury, postangioplasty endothelial regeneration, degeneration of venous bypass grafts, pure spastic angina, hypertension and diabetes. It is associated with decreased production of EDRF/NO, which probably contributes significantly to the aggravation of endothelial and parietal lesions and to the natural progression of atherosclerotic disease in general. This article describes the principal vasoactive factors secreted by the endothelium and goes on to list the physiologic cardiovascular effects of EDRF/NO in detail, and to review the different pathologies associated with a disorder of secretion of this factor.

Endothelins↗

PubMed2001

Effects of blood pressure and glucose on endothelial function.

Hypertension and diabetes mellitus are associated with accelerated atherosclerosis and an increased prevalence of cardiovascular disease. Loss of the modulatory role of the endothelium can be considered the link between these conditions and cardiovascular disease. Substantial evidence suggests that vasodilation mediated by endothelium-derived nitric oxide (NO) is impaired in animal models and in patients with hypertension and diabetes mellitus. NO is a principal factor involved in the anti-atherosclerotic properties of the endothelium. Therefore, the pathogenesis of hypertensive and diabetic vascular disease may involve a reduced bioavailability of endothelium-derived NO. Inactivation of NO by reactive oxygen species is an important common mechanism by which endothelial dysfunction may occur. This review summarizes experimental and clinical evidence for impaired NO-mediated vasodilation in the presence of high blood pressure and hyperglycemia. A better understanding of the mechanisms leading to endothelial dysfunction may unmask new preventive strategies to reduce cardiovascular morbidity and mortality in these conditions.

Animals↗

PubMed2004

Demethylbellidifolin preserves endothelial function by reduction of the endogenous nitric oxide synthase inhibitor level.

The present study examined the anti-oxidation and protective effects of demethylbellidifolin (DMB), a xanthone compound extracted from swertia davidi Franch, on endothelium. The relationship between the protective effects of DMB on endothelium and the level of asymmetric dimethylarginine (ADMA), an endogenous inhibitor of nitric oxide synthase, was also determined in the present study. DMB significantly inhibited Cu(2+)-induced low-density lipoprotein (LDL) oxidation and scavenged DPPH radicals. DMB significantly attenuated the inhibition of endothelium-dependent vasodilator responses, induced by lysophosphatidycholine (LPC) in vitro and LDL in vivo, and increased release of lactate dehydrogenase induced by LDL in cultured endothelial cells. DMB significantly attenuated the increased concentration of malondialdehyde and ADMA, and the decreased level of nitric oxide induced by LDL in vivo and in cultured endothelial cells. DMB also significantly reduced the decreased activity of dimethylarginine dimethylaminohydrolase (DDAH) induced by LDL in cultured endothelial cells. In summary, the present results suggest that DMB protects endothelial damage induced by LPC in vitro and LDL in vivo or in endothelial cells, and the protective effect of DMB on the endothelium is related to reduction of ADMA concentration via an increase of DDAH activity by inhibition of lipid peroxidation.

Animals↗