The study focuses on the mechanisms of endothelial dysfunction in the uremic milieu. Subcutaneous resistance arteries from 35 end-stage renal disease (ESRD) patients and 28 matched controls were studied ex-vivo. Basal and receptor-dependent effects of endothelium-derived factors, expression of endothelial NO synthase (eNOS), prerequisites for myoendothelial gap junctions (MEGJ), and associations between endothelium-dependent responses and plasma levels of endothelial dysfunction markers were assessed.
View Article and Find Full Text PDFWe investigated an effect of uraemia on structural and functional features of human resistance vasculature. Arteries (≈ 200 μm) isolated from subcutaneous fat biopsies obtained from 35 ESRD (end-stage renal disease) patients starting peritoneal dialysis and 30 matched controls were studied using isolated small artery bioassays. Flow-mediated dilatation was attenuated in ESRD patients compared with controls.
View Article and Find Full Text PDFStatins are believed to exert beneficial effects against cardiovascular disease beyond correction of dyslipidemia. There are however still very sparse data on how individual statins interact with the production of vasoactive eicosanoids and nitric oxide (NO) in human vascular endothelial cells. Here we have determined how fluvastatin affects the mRNA expression of genes associated with vascular reactivity as well as the formation of two major vasodilators, prostacyclin (PGI2) and NO, in human endothelial cells.
View Article and Find Full Text PDFThis ex vivo study focuses on the mechanisms of endothelium-dependent dilatation in the uterine circulation of normal pregnancy (n = 12) and in women with preeclampsia (n = 12). Arteries (internal diameter, ∼250 μm) isolated by myometrial biopsy from women undergoing planned cesarean delivery or delivery as a result of the deterioration of preeclampsia were studied using a wire myograph. Bradykinin-induced dilatation was assessed in the presence and/or absence of pharmacological inhibitors to determine the contribution of nitric oxide and endothelium-derived hyperpolarizing factor (EDHF), as well as that of EDHF-mediated pathways such as myoendothelial gap junctions (MEGJs) and products of arachidonic acid, H(2)O(2) and cytochrome P450 2C9 (CYP2C9).
View Article and Find Full Text PDFProtective role of estrogens (E2) against cardiovascular disease has been appreciated for many years until the equivocal results of cardiovascular outcomes in clinical trials on hormone replacement therapy were reported. Although new ongoing trials aim to resolve these discrepancies, it is obvious that cardiovascular effects of E(2) are complex and diverse. To understand further the cardiovascular effects of E(2), the detailed knowledge on the specific role of both classical estrogen receptor (ER) subtypes and G protein-coupled receptor-30 in the vasculature are of importance.
View Article and Find Full Text PDFAm J Obstet Gynecol
December 2008
Objective: This study was undertaken to study vascular reactivity of small myometrial arteries in women with idiopathic menorrhagia.
Study Design: Small myometrial arteries were isolated from 6 patients with idiopathic menorrhagia and 4 controls. The contractile responses to thromboxane mimetic (U46619) and endothelin-1 were assessed before and after incubation with N(w)-nitro-L arginine methyl ester alone or in combination with indomethacin (Indo).
The endothelium maintains vascular homeostasis through the release of active vasodilators. Although nitric oxide (NO) is recognized as the primary factor at level of conduit arteries, increased evidence for the role of another endothelium-derived vasodilator known as endothelium-derived hyperpolarizing factor (EDHF) has accumulated in the last years. Despite the ongoing debate of its intriguingly variable nature and mechanisms of action, the contribution of EDHF to the endothelium-dependent relaxation is currently appreciated as an important feature of "healthy" endothelium.
View Article and Find Full Text PDFThe understanding of the basis of gender differences in vascular function is of critical importance to establish gender targeted interventions in cardiovascular medicine. In this review we concentrate on the central role of the endothelium in respect to gender differences in cardiovascular physiology and pathophysiology. The role of estrogen and its receptors is introduced not only as key players in gender-related differences in incidence of cardiovascular abnormalities but also in endothelium-dependent maintenance of vascular tone through the release of endothelium-derived vasodilators and vasoconstrictors.
View Article and Find Full Text PDFAm J Physiol Heart Circ Physiol
March 2008
The objectives of this study were to determine whether placental growth factor (PlGF) exerts a vasodilatory effect on rat uterine vessels (arcuate arteries and veins) and to examine regional differences in reactivity by comparing these responses to those of comparably sized mesenteric vessels. We also sought to examine and compare its effects on human uterine and subcutaneous vessels. All vessels were studied in vitro, under pressurized (rat) or isometric wire-mounted (human) conditions, and exposed to a range of PlGF concentrations.
View Article and Find Full Text PDFAm J Physiol Regul Integr Comp Physiol
February 2008
We hypothesized that in preeclampsia (PE), contribution of endothelium-derived hyperpolarizing factor (EDHF) and the mechanism/s of its action differ from that in normal pregnancy (NP). We aimed to assess endothelial function and morphology in arteries from NP and PE with particular focus on EDHF. Arteries ( approximately 200 mum) were dissected from subcutaneous fat biopsies obtained from women undergoing cesarean section.
View Article and Find Full Text PDFRadiat Prot Dosimetry
July 2007
This study was designed to investigate the dose-rate dependent effects of ionising radiation on endothelium- and NO-mediated reactivity of aorta and coronary vessels. Rats were exposed to acute ((137)Cs, 9 x 10(-4) Gy s(-1), 18 min) and chronic ((137)Cs, 2.8 x 10(-7) Gy s(-1), 41 days) radiation in 1 Gy dose.
View Article and Find Full Text PDFThe role of gap junctions in endothelium-derived hyperpolarizing factor (EDHF)-mediated relaxation of human arteries was assessed using connexin mimetic peptides (CMPs) designated (37,43)Gap27, (40)Gap27, and (43)Gap26 according to homology with the major vascular connexins (Cx37, Cx40, and Cx43). Resistance arteries were obtained from subcutaneous fat biopsies of healthy pregnant women undergoing elective cesarean section. Endothelium-dependent vasodilatation to bradykinin (BK) was assessed using wire myography.
View Article and Find Full Text PDFSex related differences in cardiovascular function have been reported in oestrogen receptor beta knockout (ERbetaKO) mice. In this study we examined the role of endothelium-derived hyperpolarizing factor (EDHF) in differences in small artery endothelial function between ERbetaKO and wild-type (WT) mice. Small femoral arteries were isolated from ERbetaKO and WT mice and mounted on a wire myograph.
View Article and Find Full Text PDFAm J Physiol Heart Circ Physiol
May 2006
The aim of this study was to investigate acute vasodilator responses to phytoestrogens and selective estrogen receptor-alpha (ERalpha) agonist in isolated small arteries from men with established coronary heart disease (CHD) and with a history of myocardial infarction versus healthy male control subjects. As to methodology, small arteries obtained from subcutaneous fat biopsies and mounted on a wire myograph were preconstricted with norepinephrine, and dilator responses to increasing nanomolar-micromolar concentrations of the phytoestrogens resveratrol and genistein (predominantly ERbeta agonists) and to propyl-[1H]-pyrazole-1,3,5-triyl-trisplenol (PPT, a selective ERalpha agonist) were determined. These were compared with responses to reference compound 17beta-estradiol (17beta-E2).
View Article and Find Full Text PDFEstrogen receptor-beta knockout mice become hypertensive as they age, and males have a higher blood pressure than females. We hypothesized that the absence of estrogen receptor-beta may contribute to development of cardiovascular dysfunction by modification of adrenergic responsiveness in the peripheral vasculature. Small femoral arteries (internal diameter <200 microm) were isolated from estrogen receptor-beta knockout and wild-type mice and mounted on a wire myograph.
View Article and Find Full Text PDFCell Mol Biol (Noisy-le-grand)
September 2005
Endothelium- and NO-dependent relaxation of aortic segments and basal coronary flow and response of coronary vessels to exogenous NO in the Langendorff-perfused rat hearts were examined on the 3rd, 10th, 30th and 90th days following whole body irradiation in 1 Gy dose with different dose rate. NO-mediated elevation of coronary flow and increased aortic endothelium-dependent vasodilation were found at the early stage after acute irradiation (137Cs, 9 x 10(-4) Gy/s), while vascular reactivity to exogenous NO was not changed. Chronic irradiation (137Cs, 2.
View Article and Find Full Text PDFAm J Physiol Regul Integr Comp Physiol
June 2004
We studied the importance of endothelium-derived hyperpolarizing factor (EDHF) vs. nitric oxide (NO) and prostacyclin (PGI(2)) in bradykinin (BK)-induced relaxation in isolated small subcutaneous arteries from normal pregnant women. We also explored the contribution of cytochrome P-450 (CYP450) product of arachidonic acid (AA) metabolism, hydrogen peroxide (H(2)O(2)), and gap junctions that have been suggested to be involved in EDHF-mediated responses.
View Article and Find Full Text PDFVopr Kurortol Fizioter Lech Fiz Kult
December 2002
73 patients with compression-ischemic myeloradiculopathy received treatment including infrared laser radiation on the paravertebral fields, motor points of the affected nerves and biologically active points Y63, Y67, YB34, YB42, YB43, E34, E42 (1.0-5.0 mW/cm2; 5 and 5000 Hz), electrostimulation of motor nerve points and innervated by them muscles by double square impulses with a fixed gap 5 ms.
View Article and Find Full Text PDFIt is shown on isolated aorta preparations that prolonged gamma-irradiation of rats results in depression of endothelium-dependent and endothelium-independent vasodilatation responses to beta-adrenoceptors stimulation by isoprenaline and M-cholinoceptors by carbachol.
View Article and Find Full Text PDFRadiats Biol Radioecol
June 1995
It is shown on isolated aorta preparations, that external gamma-irradiation of rats in dose 6 Gy results in intensification of endothelium-dependent relaxation which reaches of maximum in 30th days of post-radiation period. Constriction effect of norepinephrine on preparations without endothelium in remote terms after irradiation decreases with maximum on 90th days.
View Article and Find Full Text PDFIt was shown with endothelium-containing and endothelium-denuded aorta segments that external gamma-irradiation of rats (6.0 Gy) results in intensification of vasodilatation reactions on beta-adrenoceptor stimulation by isoprenaline with maximum in 30th day of post-radiation period. This post-radiation alteration is not related with endothelium-derived relaxing factor.
View Article and Find Full Text PDF