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Endothelial Factor (endothelial + factor)

Distribution by Scientific Domains

Medical Sciences	75%

Selected Abstracts

Endothelium-derived hyperpolarizing factor as an in vivo back-up mechanism in the cutaneous microcirculation in old mice

THE JOURNAL OF PHYSIOLOGY, Issue 2 2007
Marie Line Gaubert
There is now strong evidence that an endothelium-derived hyperpolarizing factor (EDHF), other than nitric oxide (NO) or prostaglandin (PG), exists for dilating arteries and arterioles. In vitro studies on isolated vessels pointed out a role for EDHF as a back-up mechanism when the NO pathway is impaired, but there was a lack of in vivo studies showing a functional role for EDHF. Ageing has pronounced effects on vascular function and particularly on endothelium-dependent relaxation, providing a novel situation in which to assess the contributions of EDHF. The purpose of the present study was thus to determine if, in vivo, there was a functional role for EDHF as a back-up mechanism in the cutaneous microcirculation in the ageing process. We investigated in vivo the contribution of each endothelial factor (NO, PG and EDHF) in the cutaneous vasodilatation induced by iontophoretic delivery of acetylcholine and local pressure application in young adult (6,7 months) and old (22,25 months) mice, using pharmacological inhibitors. The cutaneous vasodilator responses induced by acetylcholine and local pressure application were dependent upon NO and PG pathways in young adult mice, whereas they were EDHF-dependent in old mice. EDHF appears to serve as a back-up mechanism when ageing reaches pathological states in terms of the ability for NO and PG to relax cutaneous microvessels, allowing for persistent cutaneous vasodilatator responses in old mice. However, as a back-up mechanism, EDHF did not completely restore cutaneous vasodilatation, since endothelial responses were reduced in old mice compared to young adult mice. [source]

3121: Oxygen and treatment of ocular ischemic diseases

ACTA OPHTHALMOLOGICA, Issue 2010
E STEFANSSON
Purpose In ischemia, reduced blood flow results in hypoxia. Hypoxic cells make hypoxia inducible factor (HIF), which controls many of the adaptive responses of tissue to ischemia. This includes vasodilatation, production of vascular endothelial factor (VEGF) with neovascularization and leakage, and finally apoptosis and tissue atrophy. Methods If hypoxia is improved this will reduce the production of VEGF and thereby reduce new vessel formation on one hand and vascular leakage and edeam formation on the other. Several methods are available to improve retinal hypoxia, including laser treatment, vitrectomy, vasodilatory drugs such as carbonic anhydrase inhibitors in addition to breathing oxygen. These treatment methods have been studied by many research groups with invasive polarographic electrodes and optical probes as well as noninvasive oxymetry in human patients and animal subjects. Results We will review experimental and clinical studies, which confirm that oxygen tension of the retina is increased following 1. retinal laser treatment 2. Vitrectomy 3. carbonic anhydrase inhibitors Conclusion Oxygen is the natural control of VEGF. VEGF levels in the retina and other ocular tissues are affected by oxygen levels and ischeimc diseases are currently treated with methods that affect oxygen and consequently VEGF. The addition of anti VEGF drugs to oxygen directed treatment such as laser and vitrectomy further influences the oxygen-HIF-VEGF-neovascularization/edema axis in ischemic retinopathies. [source]

Characterization of endothelial factors involved in the vasodilatory effect of simvastatin in aorta and small mesenteric artery of the rat

BRITISH JOURNAL OF PHARMACOLOGY, Issue 6 2000
Maria Álvarez De Sotomayor
Vascular effects of the 3-hydroxy-3-methylglutaryl-coenzyme A (HMG-CoA) reductase inhibitor, simvastatin, were studied in conductance (aorta) and resistance vessels (branch II or III of superior mesenteric artery, SMA) of the rat (12,14 weeks old). Simvastatin produced relaxation of both aorta and SMA, with and without functional endothelium. These responses were inhibited by the product of HMG-CoA reductase, mevalonate (1 mmol l,1). In vessels with functional endothelium, the NO-synthase inhibitor, L -NG -nitroarginine (L -NOARG, 30 ,mol l,1), inhibited simvastatin-induced relaxation. In the presence of L -NOARG, relaxation to simvastatin was lower in vessels with endothelium than in endothelium-denuded arteries without L -NOARG. The cyclo-oxygenase inhibitor, indomethacin (10 ,mol l,1), abolished endothelium-dependent component of the response to simvastatin in both arteries. The combination of L -NOARG plus indomethacin did not produce further inhibition. The Tp receptor antagonist, GR 32191B (3 ,mol l,1), did not affect relaxation in aorta but it reduced response to low concentrations of simvastatin in SMA. However, the inhibitory effect of L -NOARG was less marked in the presence of GR 32191B in aorta but not in SMA. The endothelium-dependent relaxation to simvastatin was inhibited by the superoxide dismutase (SOD, 100 u ml,1) or by the tyrosine kinase inhibitor, genistein (30 ,mol l,1) in the two arteries. The present study shows that simvastatin produces relaxation of conductance and small arteries through mevalonate-sensitive pathway. The endothelium-dependent relaxation to simvastatin involves both NO and vasodilator eicosanoids by a mechanism sensitive to SOD, and to genistein. Also, the results highlighted participation in the aorta of endothelial vasoconstrictor eicosanoids acting on the Tp receptor after blockage of NO synthase only. British Journal of Pharmacology (2000) 131, 1179,1187; doi:10.1038/sj.bjp.0703668 [source]

Endothelial markers and homocysteine in patients with classic Fabry disease

ACTA PAEDIATRICA, Issue 2002
K Demuth
Aim: Fabry disease is an X-linked inborn error of glycosphingolipid metabolism due to the deficient activity of ,-galactosidase A, a lysosomal enzyme. It is a multisystem disorder characterized by progressive renal insufficiency, with added morbidity from cardio- and cerebrovascular involvement. The recent availability of genetically engineered enzyme offers an effective targeted treatment approach, but also emphasizes the need for surrogate markers to delineate organ damage and monitor the efficacy of enzyme replacement therapy (ERT). Methods: Multiple endothelial factors and plasma homocysteine concentrations were investigated in 12 consecutive hemizygous males with classic Fabry disease and 15 controls as part of an exhaustive baseline evaluation prior to ERT. Results: Compared with the controls, plasma concentrations of homocysteine were significantly (p > 0.01) higher in patients with Fabry disease in the absence of chronic renal failure or vitamin deficiency. Plasma concentrations of vascular cell adhesion molecule-1 were also significantly (p > 0.05) higher in the patients, and there was a trend for decreased endothelin-1 levels. No difference was found in serum intercellular adhesion molecule-1, plasma P-selectin, serum E-selectin and plasma thrombomodulin between the patients and controls. Conclusions: The results do not reveal measurable evidence for endothelial and leukocyte activation that could reliably serve as surrogate markers for routine monitoring of the efficacy of ERT in patients with Fabry disease. While the exact origin and clinical significance of hyperhomocysteinaemia in Fabry disease remains to be studied in a larger cohort of patients carefully monitored for their concurrent medications, especially carbamazepine, we suggest that patients may benefit from folic acid or multivitamin therapy to treat this additional vascular risk factor, when present. [source]