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Query: UNIPROT:P06889 (Mol)
 630,302 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Recent studies have shown that the vasodilatory response of adenosine is partially endothelium dependent. Therefore, to further characterize the physiologic role of the vascular endothelium as mediator of adenosine's cardiovascular effects, we have examined in isolated perfused guinea-pig hearts the dromotropic and vascular effects of adenosine in the presence of the adenosine antagonist, XAC, covalently conjugated to latex microspheres of 0.07 microns diameter. Our results demonstrate that intravascular infusion of the microsphere XAC conjugates abolishes the vasodilatory and negative dromotropic effects of infused adenosine, and inhibits the dromotropic effects of hypoxia. As these particles because of their size remain intravascularly confined, we conclude that the dromotropic and vasodilatory effects of exogenous adenosine, and the dromotropic effects of hypoxia (endogenous adenosine), arise from the intravascular adenosine compartment acting by way of the vascular endothelium. In addition, while neither the temporal course of vasodilation nor the steady state of vasodilation caused by hypoxia were influenced by unconjugated XAC, our results do show that the microsphere XAC conjugate increases the time necessary for maximum vasodilation to occur during hypoxia.
J Mol Cell Cardiol 1993 Jun
PMID:Implications of the coronary vascular endothelium as mediator of the vasodilatory and dromotropic actions of adenosine. 841 Nov 95

Endothelin (ET), a potent vasoconstrictor and bronchoconstrictor peptide synthesized by endothelial and epithelial cells, was examined for its potential functions in human inferior turbinate nasal mucosal tissue by four techniques: (1) immunoreactive ET was localized in the mucosa by immunohistochemistry; (2) receptors for ET were identified by autoradiography employing [125I]ET; (3) ET-1 mRNA was localized by in situ hybridization; and (4) the secretory functions of ET were examined by the release of mucous and serous cell products after the addition of ET to human nasal turbinates in short-term cultures. Specific ET-1-immunoreactive material was found most extensively in small muscular arteries and in serous cells in submucosal glands. ET-1 was also found to a lower extent in the walls of venous sinusoids. [125I]ET-1 binding sites were localized by autoradiography to submucosal glands and to venous sinusoids and small muscular arterioles. mRNA for ET-1 was found most extensively in the venous sinusoids and to a lesser extent in small muscular arteries. In mucosal explant cultures, ET-1 and ET-2 stimulated lactoferrin and mucous glycoprotein release from serous and mucous cells, but ET-3 was inactive. The observations indicate that in the human nasal mucosa, ET is present in the vascular endothelium and the serous cells in submucosal glands and acts on glandular ET receptors to induce both serous and mucous cell secretion. It is also likely that ET plays a role in the regulation of vasomotor tone.
Am J Respir Cell Mol Biol 1993 Apr
PMID:Endothelin in human nasal mucosa. 847 33

The endothelium profoundly affects subjacent vascular smooth muscle function. An analogous relationship between endothelial endocardial cells (EEC) and the myocardium is suggested by Brutsaert et al.'s observation that EEC modulate the contractility of subjacent myocardium. Prostanoids are a major product by which vascular endothelium affects smooth muscle, but similar prostanoid production by EEC has not been described. To determine whether both right and left ventricular EEC produce prostacyclin (PGI2) and prostaglandin E2 (PGE2), ovine EEC were cultured. EEC prostanoid production was measured under basal conditions and after stimulation with arachidonic acid or calcium ionophore A23187. EEC from both ventricles demonstrated sustained prostacyclin and PGE2 production. Prostacyclin production was 10 times greater than PGE2. These results suggest that endocardial prostanoid production could act both locally, to modulate platelet and myocardial function, and distally, on downstream vascular tone.
J Mol Cell Cardiol 1993 Mar
PMID:Right and left ventricular cultured endocardial endothelium produces prostacyclin and PGE2. 851 Jan 68

The purpose of this study was to compare coronary and interstitial endothelin-1 (ET-1) levels in perfused rat hearts under several experimental conditions, because the cardiac tissue concentration of ET-1 is not clear. Hearts were perfused in an upside-down position with a colloid-free buffer at a constant flow rate of 9 ml/min/g heart wet weight, and immunoreactive ET-1 was determined in timed collections of coronary effluent and interstitial transudate produced by the ventricles and appearing on their surface. Basal ET-1 release into effluent was 0.26 +/- 0.007 pg/min/g, and 0.005 +/- 0.0012 pg/min/g in transudate. Basal ET-1 concentration was 0.11 +/- 0.005 pg/ml (transudate) and 0.03 +/- 0.002 pg/ml (effluent), indicating four-fold higher transudate than effluent levels (P < 0.05). Following perfusion of hearts with collagenase to remove endothelial cells, ET-1 release into effluent was reduced to one-third and completely abolished in transudate, indicating that the peptide originated from the vascular endothelium. Perfusion of hearts with angiotensin II (0.1 mumol/l) or thrombin (5 U/ml) increased coronary perfusion pressure and ET-1 secretion, but little affected the transudate/effluent ET-1 concentration ratio (5.5 and 3.2, respectively). When coronary flow was reduced to ischaemic level (1 ml/min/g over several hours), ET-1 secretion rates into effluent were decreased by 55-65%, but increased three- to four-fold on reperfusion at normal flow (P < 0.05). The ET-1 concentrations in both fluids were still always below 1 pg/ml. No change in coronary perfusion pressure compared to time-matched normoxic controls was observed. In the presence of the ET-1 converting enzyme inhibitor, phosphoramidon (1.7 mumol/l), ischaemia-induced increases of ET-1 secretion were attenuated, and this was accompanied by a time-dependent rise in coronary perfusion pressure up to 60% (P < 0.05). These are the first measurements of endogenous cardiac tissue ET-1 levels; they do not support a vasoconstrictor (pro-ischaemic) action of endogenous ET-1 in rat hearts following ischaemia/reperfusion, but rather point to a possible vasodilator role of the peptide under these conditions.
J Mol Cell Cardiol 1995 Sep
PMID:Tissue endothelin-1 levels in perfused rat heart following stimulation with agonists and in ischaemia and reperfusion. 852 55

Recent in vitro studies have suggested that interleukin-4 (IL-4) may be involved in the preferential migration of eosinophils into the airways in allergic asthma through its capacity to selectively increase vascular cell adhesion molecule-1 (VCAM-1) expression on vessels. To test this hypothesis, we studied the expression of VCAM-1, E-selectin, and intercellular adhesion molecule-1 (ICAM-1) on vascular endothelium in bronchial mucosal biopsies from 20 allergic asthmatics using an immunohistochemistry technique and related the observations to IL-4 levels in bronchoalveolar lavage (BAL) fluid simultaneously obtained and to eosinophil infiltration in the bronchial mucosa. IL-4 was detectable in BAL fluid from nine subjects (range, 15.1 to 110 pg/ml in 20-fold concentrated BAL fluid) (IL-4-positive asthmatics) but unmeasurable in the remaining 11 subjects (IL-4-negative asthmatics). The IL-4-positive asthmatics showed a significantly increased expression of VCAM-1 but not E-selectin and ICAM-1 on vessels as compared with both IL-4-negative asthmatics (P < 0.001) and diseased control subjects (P < 0.001). In asthmatics, VCAM-1 expression was positively correlated with BAL IL-4 levels (rs = 0.89; P < 0.0001). Moreover, there was a significant correlation between the endothelial expression of VCAM-1 and the number of eosinophils, but not neutrophils, in the bronchial submucosa (r2 = 0.76; P < 0.001). A significant correlation was also found between BAL IL-4 levels and the number of eosinophils. These results suggest that IL-4 is a VCAM-1-selective activator also in human airways and the VCAM-1-dependent pathways play a role in selective migration of eosinophils into the airways in allergic asthma, and support the hypothesis described above.
Am J Respir Cell Mol Biol 1996 Jan
PMID:Role of interleukin-4 and vascular cell adhesion molecule-1 in selective eosinophil migration into the airways in allergic asthma. 853 90

The effect of zinc on the repair of wounded monolayers of bovine aortic endothelial cells in a culture system was investigated. It was morphologically found that zinc promotes the appearance of the cells in the wounded area; cell number in the area was significantly increased by zinc. However, other heavy metals including copper, manganese, nickel and cobalt failed to exhibit a similar effect. The repair induced by exogenous basic fibroblast growth factor (bFGF) was potentiated by zinc but that by exogenous acidic fibroblast growth factor was unaffected by the metal. Promotion of the repair of the wounded area by zinc was completely blocked by either cycloheximide or anti-bFGF antibody. In addition, zinc-induced repair was significantly inhibited by a lipoxygenase inhibitor, nordihydroguaiaretic acid but not by a cyclooxygenase inhibitor, indomethacin. From these results, it is suggested that zinc promotes the repair process of damaged vascular endothelium through the lipoxygenase pathway that mediates the response of vascular endothelial cells to endogenous bFGF.
Res Commun Mol Pathol Pharmacol 1995 Aug
PMID:Zinc promotes the repair of wounded monolayers of cultured vascular endothelial cells. 855 73

To evaluate the airway infiltration of eosinophils in the asthmatic responses of Brown-Norway rats, which were sensitized with ovalbumin, the time course of eosinophil infiltration and respiratory resistance (Rrs) after ovalbumin challenge was measured. The effect of treatment with monoclonal antibody against ICAM-1 and CD18 was studied. Finally, the expression of ICAM-1 and CD18 in the airway was investigated. All rats showed Rrs increase 6-7 hours after ovalbumin challenge, indicating a late asthmatic response (LAR). Animals with LAR had higher eosinophil counts than those with an immediate asthmatic response (IAR) and in the sensitized but nonchallenged animals. Rats treated with the antibodies showed significantly smaller increases in Rrs and lower eosinophil counts than the control animals. Immunohistochemical staining in airway was performed. ICAM-1 immunoreactivity was positive on both the epithelium and the vascular endothelium of a trachea section, and on the pulmonary vascular endothelium. ICAM-1 expression was upregulated after challenge. The number of CD18-positive cells in sections of trachea and lung increased after challenge. Our results show that eosinophil infiltration is important in LAR development and the treatment with antagonists of ICAM-1 and CD18 may provide a therapeutic approach to reducing asthmatic symptoms.
Res Commun Mol Pathol Pharmacol 1995 Oct
PMID:Role of eosinophils and cell adhesion molecules in the allergen-induced asthmatic response of rats. 858 46

The role of monocytes as initiators of coagulation through the expression of tissue factor has been well documented in vitro, and the relationship of monocyte tissue factor to the thrombotic complications of atherosclerosis has been suggested. Tissue factor antigen has been identified in the plasma membranes of monocytes adherent to the vascular endothelium overlying atherosclerotic plaques and the presence of tissue factor in adherent mononuclear cells correlates with the polymerization of fibrin at these same sites. To further understand the relationship of cellular adhesion to tissue factor expression, human monocytes were cocultured for periods ranging from 30 min to 24 hr with endothelial cells isolated from human umbilical veins (HUVEC). Tissue factor antigen, as assayed by both ELISA and immunogold electron microscopy, was minimal on either monocytes or HUVEC maintained in homogeneous cultures or on the cells when cocultured for 1 hr or less. This was true whether the HUVEC were in a native state or if they had been stimulated with interleukin-1 (IL-1 beta) or lipopolysaccharide (LPS) prior to monocyte adhesion. Typically, less than 13% of the cells in short-term cocultures were positively labeled through anti-tissue factor immunogold microscopy. The level of tissue factor, however, was increased 3-fold above baseline when monocytes were cocultured with unstimulated HUVEC for 4 hr, and it was more than double this if the HUVEC had been exposed to IL-1 beta or LPS (7-fold increase). By 24 hr, the expression of tissue factor antigen was nearly 50-fold higher in cocultures involving stimulated HUVEC, and at later times greater than 70% of the cells were labeled with immunogold. Through the use of quantitative immunogold electron microscopy, the increase in tissue factor was most pronounced on monocytes which had three times greater increase in tissue factor than HUVEC in the same cultures. These studies document the stimulation of tissue factor expression by monocytes upon coculture with endothelial cells, and the data document an enhancement of this coculture effect upon HUVEC stimulation with cytokines. These observations have relevance to atherosclerotic disease by suggesting that interaction of monocytes with dysfunctional endothelial cells overlying atherosclerotic plaques would be sufficient to induce tissue factor and by so doing predispose to localized thrombotic events.
Exp Mol Pathol 1995 Jun
PMID:Tissue factor expression during coculture of endothelial cells and monocytes. 861 25

Factors that influence the development of the normal pulmonary vasculature are poorly understood. Since increased local production of angiotensin II (AII) by angiotensin converting enzyme (ACE) has been implicated in the medial hypertrophy of systemic and pulmonary hypertension, we questioned whether ACE and angiotensin receptor expression may influence the muscularization of the normal pulmonary vasculature during development. The approach employed measurement of lung ACE activity, assessment of local ACE expression by immunohistochemistry, and angiotensin type 1 receptor (AT1) expression by in situ hybridization in rat lungs ranging from 15 days of intrauterine life (term = 21 d) to adulthood. The temporal and spatial pattern of ACE expression was compared with that of the endothelial marker, von Willebrand factor (vWF), and the smooth muscle cell markers, alpha smooth muscle actin and smooth muscle myosin. ACE activity was first detected in lung homogenates on day 17 of gestation (1 +/- 0.2 mU/mg) and increased progressively to term (27.7 +/- 3.2 mU/mg). However, the greatest increase in lung ACE activity to adult levels (379 +/- 25.2 mU/mg) occurred between 2 and 4 wk of postnatal life. Immunohistochemistry demonstrated vWF expression by vascular endothelium throughout the lung as early as day 15 of gestation. In contrast, ACE expression was observed in the endothelium of only hilar pulmonary arteries on day 15 of gestation, and thereafter was noted to be expressed in endothelial cells of progressively more distal arteries, such that by term, endothelial cells of all muscularized arteries expressed ACE. Alveolar capillary ACE expression was not detected until day 20 of gestation, and increased dramatically after birth. Smooth muscle actin expression in lung arteries closely paralleled the expression of endothelial ACE. AT1 receptor mRNA was first expressed in the peripheral lung on day 17 of gestation by non-epithelial undifferentiated mesenchyme. In contrast, AT1 mRNA signal was much reduced in differentiated smooth muscle. We speculate that ACE expression in the fetal lung circulation may influence the muscularization of fetal pulmonary arteries by the interaction of locally produced angiotensin II with the AT1 receptor.
Am J Respir Cell Mol Biol 1996 Jun
PMID:Developmental regulation of angiotensin converting enzyme and angiotensin type 1 receptor in the rat pulmonary circulation. 865 81

Rat Langendorff hearts perfused with media that do not contain erythrocytes or fluorocarbon as oxygen carriers are borderline aerobic during 5 Hz pacing. This follows from the release of catabolic products measured: lactate, urate and Iysophosphatidyl-choline (IysoPC). Addition of L-carnitine to the perfusion medium reduced the level of these compounds, while the release of long-chain acylcarnitine (LCAC) increased. Previously, we found (Biochim Biophys Acta 847:62-66,1985) that micromolar LCAC protects membranes during reperfusion after ischemia. Therefore, the observed inverse relation between LCAC and the other compounds measured suggests that LCAC is the basis of an acute relief of imminent ischemia by carnitine addition. LCAC may be released from various cell types, including vascular endothelium, as demonstrated. The cationic amphiphilic nature of LCAC is responsible for protection of membrane functions in imminent ischemia.
Mol Cell Biochem 1996 Mar 09
PMID:Release of ischemia in paced rat Langendorff hearts by supply of L-carnitine: role of endogenous long-chain acylcarnitine. 870 80


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