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Query: UMLS:C0406810 (NAME)
 13,345 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

1. This article examines the effects of hypoxia on the contractile response of isolated human umbilical artery strips to 5-hydroxytryptamine (5-HT). 2. Hypoxic conditions produce a large increase in the contractile response to 5-HT without a significant alteration of the sensitivity evaluated at the level of the pD2 value. Indomethacin (10 microM) reduced hypoxia-induced potentiation of the response to 5-HT and decreased the response to the monoamine under oxygenated conditions. 1-NAME (100 microM) did not further increase the effect of hypoxia on the vessel response to 5-HT and increased the response to 5-HT under oxygenated conditions. 3. Taken together, these results suggest that, at least partially, the response of human umbilical artery strips to 5-HT depends on 5-HT release of a contracting prostanoid which is a product of the cyclooxygenase pathway. Furthermore, during hypoxia in human umbilical artery strips, there appears to be impairment of the basal production and/or release of EDRF/NO. 4. A subthreshold concentration of prostaglandin F2 alpha (1 nM) potentiates the response to 5-HT in indomethacin-pretreated umbilical artery strips. The data raise the possibility that prostaglandin F2 alpha might be the prostanoid released during hypoxia, which in turn potentiates the response of the human umbilical artery to 5-HT.
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PMID:Hypoxia and response of human umbilical artery strips to 5-hydroxytryptamine: role of prostaglandin F2 alpha. 911 81

The purpose of this study was to assess the anti-platelet properties of endocardial endothelial cells (EECs) by measuring platelet aggregation after a brief incubation with cultured EECs. EECs were isolated from the right ventricles of porcine hearts and coronary artery endothelial cells (C-ECs) were also isolated from the same animals. After brief incubations (2-min) of platelet suspensions with cultured EEC and CEC monolayers, platelet aggregation in response to thrombin and 6-keto-PGF1 alpha (a stable metabolite of PGI2) content of platelet suspensions were measured. Platelet aggregation was significantly inhibited by a brief incubation of platelet suspensions with EEC and C-ECs monolayers. Pretreatment of EECs and C-ECs with indomethacin (5 x 10(-5) M) restored platelet activity, but pretreatment with N omega-nitro-L-arginine methyl ester (L-NAME, 5 x 10(-5) M) or hemoglobin (1 x 10(-6) M) did not. Platelet/EEC interactions multiplicatively increased the 6-keto-PGF1 alpha content of platelet suspensions and the 6-keto-PGF1 alpha content of platelet suspensions after incubations with EECs correlated significantly with the inhibition of platelet aggregation. Both the anti-aggregation properties and 6-keto-PGF1 alpha production were significantly greater in EECs than in C-ECs. A brief incubation (2-min) with PDGF (10 ng/ml) or TGF-beta (1 and 10 ng/ml) stimulated 6-keto-PGF1 alpha production in EECs but not in C-ECs, although these growth factors stimulated 6-keto-PGF1 alpha production in C-ECs after a longer incubation time (30 or 60 min). In this study, after a brief incubation (2-min) with platelet suspensions, EECs inhibited platelet aggregation mainly through the release of PGI2 but not EDRF. As this anti-aggregation property was significantly greater in EECs than in C-ECs, it is suggested that endocardial endothelial PGI2 may inhibit both intracardiac and intracoronary artery thrombus formation, contributing to the prevention of myocardial ischemia.
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PMID:Antithrombotic effects of endocardial endothelial cells-comparison with coronary artery endothelial cells. 924 71

1. The effects of simulated myocardial ischemic conditions on the contractile response of isolated human umbilical artery (HUA) strips to 5-hydroxytryptamine (5-HT) and prostaglandin F2 alpha (PGF2 alpha) were studied. 2. During simulated myocardial ischemic conditions the contractile response of HUA strips to 5-HT was lower than the response to the monoamine under oxygenated conditions. Under simulated ischemic conditions the response to 5-HT was further depressed by the cyclooxygenase inhibitor indomethacin (10 microM) and increased by the NO synthase inhibitor L-NAME (100 microM). 3. During simulated ischemic conditions the response of the HUA to a submaximal concentration of PGF2 alpha (3 microM) was reduced. Indomethacin (10 microM) further reduced the response to the prostanoid whereas L-NAME (100 microM) enhanced the response to PGF2 alpha. 4. It is concluded that during simulated myocardial ischemic conditions lactate negatively modulates the contractile response of HUA strips to 5-HT. Apparently, during simulated myocardial ischemic conditions in the HUA the production and/or release of EDRF/NO was not affected.
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PMID:Effects of simulated myocardial ischemic conditions on the responses of isolated human umbilical artery strips to 5-hydroxytryptamine and prostaglandin F2 alpha. 937 61

EDRF-NO probably participates-besides the prostaglandins [3, 4]-in local circulatory changes in the bones of female rats with modified level of sex hormones; we could demonstrate it indirectly using methylene blue as a blocking agent [5]. In this paper, we present corresponding results of two experiments with NG-nitro-arginine methyl ester (L-NAME) as a substance blocking the production of endothelium derived relaxing factor, i.e. nitric oxide (EDRF-NO). Circulatory values were estimated by means of 85Sr-microspheres. In experiment A we ascertained whether the duration of L-NAME administration (0.025% in the food) influenced the effect. It could be demonstrated that the effect of one week's, two weeks', or four weeks' administration of L-NAME was the same: 85Sr-microsphere uptake and blood flow throught the tibia of female rats, increased after oophorectomy (OOX, performed four weeks prior to the experiment), was significantly suppressed to the level in sham-operated animals. In the experiment B, L-NAME was administered in the food in concentration of 0.05% for two weeks prior to the experiment. 85Sr-microsphere uptake was decreased significantly after L-NAME in the tibia of sham-operated females, in the tibia and distal femur of OOX animals; no significant changes were found in the diaphysis of femur and in calvaria. Blood flow values were significantly decreased in all bone samples of OOX females and in tibia of sham-operated rats (besides the local reaction also due to the decrease in the cardiac output). In both experiments the cardiac output was decreased and blood pressure elevated after L-NAME. It can be concluded, from the results of both experiments, that the blockade of EDRF-NO production by L-NAME decreases local circulatory values in the bones of female rats-particularly OOX-in a similar way as methylene blue; however, in contrast to methylene blue, L-NAME induces marked increase in the blood pressure and partially decrease in the cardiac output. Thus, as in the case of methylene blue, the effect of L-NAME on the circulation of blood in the rat bones supports the hypothesis of the participation of EDRF-NO in bone blood flow regulations.
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PMID:[The role of EDRF-NO in the regulation of bone blood flow in rats: inhibition with L-NAME]. 942 10

The vascular endothelial cell is a multipotent cell which has several functions: transport barrier, phagocytosis, coagulation/anticoagulation, fibrinolysis, autocrine/paracrine and metabolic functions. The release of vasoactive agents, such as the vasodilators EDRF (NO) and EDHF, and vasoconstrictors, such as endothelin (ET), represents an important local mechanism altering the balance of vasodilation/ vasoconstriction of the vascular smooth muscle cell. Inhibition of the synthesis of NO by exogenous (e.g. L-NAME) or endogenous (e.g. ADMA) L-arginine analogues may cause transient or sustained hypertension. A similar effect may be achieved by continuous administration of the potent vasoconstrictor ET. Endothelial dysfunction, associated with a deficient NO production and release as well an enhanced ET generation, may be present in some forms of vascular disease, such as hypertension, atherosclerosis, diabetes mellitus or sleep apnea. Whether such alterations may be a cause of hypertension and involved in the maintenance of high blood pressure or whether they represent a consequence of the hypertensive disease remains to be concluded. Furthermore, while there is emerging evidence that endothelial dysfunction in cardiovascular disease may be reversed by therapy, it remains to be determined whether measures of endothelial function in man may serve as predictors for morbidity or mortality.
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PMID:Measures of endothelial function as an endpoint in hypertension? 949 29

It has been proposed repeatedly that essential hypertension as well as secondary hypertension is associated in a causative manner with endothelial dysfunction in the resistance vessels. Endothelial damage and dysfunction may be expected to attenuate the endogenous vasodilator mechanism of EDRF (nitric oxide) and hence cause a rise in blood pressure. This attractive hypothesis, put forward a few years ago, is subject to considerable debate at present. In the present survey the arguments in favour and against this hypothesis are critically discussed. The following arguments support the causative association between endothelial dysfunction: the hypertensive effect of NO-synthase blockade by L-NAME and related agents; the antihypertensive effect of L-arginine in salt-loaded Dahl rats; the impaired vasodilator effect in the forearm vascular bed of hypertensives; diminished NO-synthesis in hypertensives. However, several findings speak against the association between hypertensive disease and endothelial dysfunction. For instance: no clear demonstration of impaired endothelial function in isolated vessels of hypertensive patients and animals; studies in the human forearm vascular bed where endothelial function appears to be fully intact in hypertensives. Attempts are made to explain the discrepancies between the various findings. So far the association between endothelial dysfunction and hypertension appears to be an uncertain one.
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PMID:Endothelial dysfunction in hypertension. A critical evaluation. 949 30

The intracellular mechanisms underlying the action of the endogenous vasodilators such as NO/EDRF, adenosine, and prostacyclin acting through cGMP and cAMP, respectively, are not well understood. One important action of cyclic nucleotides in smooth muscle relaxation is to lower the cytosolic Ca2+ concentration by enhanced sequestration into the sarcoplasmic reticulum. The present study was undertaken to elucidate the potential role of phosphorylation of phospholamban, the regulator of sarcoplasmic reticulum Ca2+ pump, for the control of coronary vascular tone by NO/EDRF, adenosine, and prostacyclin. Phospholamban was identified in pig coronary artery preparations by immunofluorescence microscopy, Western blotting and in vitro phosphorylation. Segments of pig coronary artery, with either intact or denuded endothelium, were precontracted with prostaglandin F2alpha (PGF2alpha). In endothelium-denuded preparations 3-morpholinosydnonimine (SIN-1), 5'-N-ethylcarboxiamidoadenosine (NECA), and iloprost (ILO) caused both relaxation and phospholamban phosphorylation with the potency: SIN-1 > NECA > ILO. The regulatory myosin light chain was significantly dephosphorylated only by SIN-1. In endothelium-intact pig coronary artery, L-NAME caused additional vasoconstriction and a decrease in phospholamban phosphorylation, while phosphorylation of myosin light chain remained unchanged. An inverse relationship between phospholamban phosphorylation and vessel tone was obtained. Our findings demonstrate significant phospholamban phosphorylation during coronary artery relaxation evoked by NO, prostacyclin, and adenosine receptor activation. Because of the close correlation between phosphorylation of phospholamban and vessel relaxation, we propose that phospholamban phosphorylation is an important mechanism by which endogenous vasodilators, especially endothelial NO/EDRF, control coronary vascular smooth muscle tone.
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PMID:Phosphorylation of phospholamban correlates with relaxation of coronary artery induced by nitric oxide, adenosine, and prostacyclin in the pig. 963 7

The effect of T-593, a novel antiulcer agent, was investigated with respect to gastric bleeding and lesions induced by indomethacin (3 mg/kg, s.c.) and water (23 degrees C) immersion stress (IM-WIS) with perfusion of HCl (0.13N) into the rat stomach. It was found that the total amounts of gastric bleeding and lesions after IM-WIS with perfusion of HCl were more significantly decreased in T-593 (1 mg/kg, i.v., 0.1 mg/kg/hr, d.i.)- and secretion (15 CU/kg/hr, d.i.)-treated rats, respectively. On the other hand, famotidine (1 mg/kg, i.v.) did not affect gastric bleeding and lesions. The gastric mucosal blood flow (GMBF) reduction was induced by IM-WIS. T-593 (0.03-0.1 mg/kg/hr, d.i.) inhibited the GMBF reduction dose-dependently. The GMBF improvement by T-593 disappeared with pretreatment of L-NAME (2 mg/kg, s.c.) and was recovered by L-arginine (50 mg/kg, i.v.). This indicates that GMBF improvement by T-593 is dependent on EDRF (NO). This interesting property of T-593 is expected to contribute to the clinical promotion of ulcer healing.
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PMID:[Effect of T-593 on gastric bleeding and lesions induced by indomethacin and water-immersion stress in rats: improving effect of T-593 on reduced gastric mucosal blood flow in rats]. 978 2

The contractile actions of the proteinase-activated receptor-2-activating peptides (PAR2APs), SLIGRL-NH2 (SL-NH2), SLIGKV-NH2 (KV-NH2), trans-cinnamoyl-LIGRLO-NH2 (tc-NH2), and the PAR1-AP. TFLLR-NH2 (TF-NH2) as well as trypsin and thrombin were studied in endothelium-denuded and intact human umbilical vein (HUV) ring preparations. In HUV rings with, but not without an intact endothelium, PAR2APs caused a concentration-dependent contractile response, whereas LSIGRL-NH2 trypsin and PAR1APs were inactive. The contractile response was not affected by the endothelin ETA receptor antagonist, BQ123, the cyclooxygenase inhibitor, indomethacin, the leukotriene synthesis inhibitor, MK886, or the epoxygenase/P450 inhibitor, SKF-525A. Other pharmacological antagonists (prazosin, Losartan") were similarly inactive. The order of potencies of the PAR2APs to cause a contraction in the endothelium-intact preparation was: SL-NH2 > > KV-NH2 > or = tc-NH2. Using an endothelium-free rat aorta ring as a reporter tissue, surrounded with endothelium-intact HUV as a donor tissue in a 'sandwich assay,' we also monitored the ability of SL-NH2, TF-NH2, trypsin and thrombin to release either contractile (EDCF) or relaxant (EDRF) factors. In the 'sandwich assay' done in the presence of L-NAME (0.1 mM), the endothelium-intact HUV tissue (but not endothelium-denuded HUV) released a contractile factor (EDCF) in response to SL-NH2 (50 microM) but not to trypsin or LSIGRL-NH2. The SL-NH2-mediated release/action of the EDCF was not affected by BQ123, indomethacin, MK886 or SKF-525A. In the 'sandwich assay', trypsin (4-10 nM), SL-NH2, KV-NH2 and tc-NH2 caused the release of a relaxant activity (EDRF) from the endothelium-intact (but not the denuded) HUV preparation. The release of EDRF was blocked by 0.1 mM (omega)nitro-L-arginine-methylester (L-NAME). Neither thrombin (10 u ml(-1), 100 nM) nor TF-NH2 (50 microM) were active in this EDRF-release assay. The relative potencies of the PAR2 agonists for causing the release of EDRF in the HUV sandwich assay were: trypsin> >SL-NH2> >tc-NH2>KV-NH2. This order of potencies differed from the one observed for the same agonists in the HUV contraction assay (above) and in an intracellular calcium signalling assay, conducted with cloned human PAR2 that was expressed in cultured rat kidney KNRK cells: trypsin > > SL-NH2 = tc-NH2 > KV-NH2. We conclude that PAR2APs (but not PAR1APs) via a receptor distinct from PAR2, can cause a contractile response in endothelium-intact HUV tissue via the release of a diffusable EDCF, that is different from previously recognized smooth muscle agonists (e.g. prostanoid metabolites, endothelin, noradrenaline, angiotensin-II, acetylcholine).
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PMID:Endothelium-dependent contractile actions of proteinase-activated receptor-2-activating peptides in human umbilical vein: release of a contracting factor via a novel receptor. 988 72

1. The aims of this study were to compare, in the rat isolated perfused lung preparation, the antagonist effects of a nonselective beta-adrenoceptor agonist (isoprenaline), a selective beta2-adrenoceptor agonist (salbutamol) and a selective beta3-adrenoceptor agonist (SR 59104A) on the hypoxic pulmonary pressure response, and to investigate the role of K+ channels, endothelium derived relaxing factor and prostaglandins in these effects. K+ channels were inhibited by glibenclamide, charybdotoxin or apamin, NO synthase and cyclo-oxygenase were inhibited by N(G)-nitro-L-arginine methyl ester (L-NAME) and indomethacin, respectively. 2. Hypoxic ventilation produced a significant increase in perfusion pressure (+65%, P<0.001) and L-NAME significantly increased this response further (+123%, P<0.01). After apamin, L-NAME, indomethacin, post-hypoxic basal pressure did not return to baseline values (P<0.001). 3. Glibenclamide partially inhibited the relaxant effects of isoprenaline (P<0.05) and salbutamol (P<0.001) but not that of SR 59104A. In contrast, charybdotoxin and apamin partially inhibited the relaxant effects of SR 59104A (P=0.053 and <0.01, respectively) but did not modify the effects of isoprenaline and salbutamol. L-NAME partially inhibited the dilator response of salbutamol (P<0.01) and SR 59104A (P<0.05) but not that of isoprenaline. 4. We conclude that (a) EDRF exerts a significant inhibition of the hypoxic pulmonary response, (b) SK(Ca) channel activation, EDRF and prostaglandins contribute to the reversal of the hypoxic pressure response, (c) the vasodilation induced by isoprenaline is mediated in part by activation of K(ATP) channels, that of salbutamol by activation of K(ATP) channels and EDRF. In contrast, SR 59104A partly operates through BK(Ca), SK(Ca), channels and EDRF activation, differing in this from the beta1 and beta2-adrenoceptor agonists.
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PMID:Role of potassium channels and nitric oxide in the relaxant effects elicited by beta-adrenoceptor agonists on hypoxic vasoconstriction in the isolated perfused lung of the rat. 1038 42


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