Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0034063 (pulmonary edema)
 10,665 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Endothelin-1 (ET-1) is a potent vasoactive peptide that has been reported to cause lung edema. This study tested if the edemagenic effect of ET-1 is due to preferential venoconstriction and, if so, whether the site of resistance is similar with salt solution (PSS) and more physiologic blood perfusate. ET-1 caused concentration-dependent contraction of pulmonary arterial and venous rings, with an EC50 of 1.3 nM in artery and 0.6 nM in vein (p less than 0.05). In PSS-perfused lungs, 5 nM ET-1 caused a 7.0 +/- 0.8 torr pressor response that was associated with a 5.0 +/- 0.3 torr increase in microvascular pressure and a 530 +/- 20 mg increase in lung weight within 10 min. In contrast, KCl-treated lungs had an equivalent pressor response (7.4 +/- 1.1 torr), yet the microvascular pressure increased by only 2.5 +/- 0.4 torr (p less than 0.05 from ET-1) and the lung weight was unchanged. Meclofenamate did not prevent the effect of ET-1 on microvascular pressure or lung weight. In blood-perfused lungs, ET-1 caused a 7.3 +/- 0.1 torr pressor response but only a 2.0 +/- 0.5 torr increase in microvascular pressure and no increase in lung weight. ET-1 had no effect on permeability either of cultured endothelial cell monolayers or in the pulmonary microvasculature in vivo. We conclude that the edemagenic effect of ET-1 in PSS-perfused lungs is mediated through venoconstriction and an increase in microvascular pressure.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Endothelin-1 increases the pulmonary microvascular pressure and causes pulmonary edema in salt solution but not blood-perfused rat lungs. 128 Jul 24

Serum endothelin levels increase during sepsis, ischemia, reperfusion, pulmonary operations, and systemic hypertension after surgery. Despite extensive study, the site and extent of action of endothelin on the pulmonary microcirculation are not well established. To assess the effect of endothelin on the pulmonary vasculature, especially the veins, the circulation of the lung was cast with methyl methacrylate 10 minutes after endothelin-1 was given intravenously to rats. Endothelin-1, at concentrations of 0.1, 1.0, and 10.0 micrograms/kg of body weight, increased the mean systemic arterial blood pressure 8%, 7%, and 17% (p < 0.01) and mean pulmonary arterial blood pressure 15%, 28%, and 53%, respectively (p < 0.01). The proportional increases in the pulmonary pressures were greater than those of the systemic pressures (p < 0.01). Scanning electron microscopy of cast blood vessels showed more contraction of the veins than the arteries. For doses of 0, 0.1, 1.0, and 10.0 micrograms/kg, the respective focal contraction of small veins was 6.7% (+/- 4.4), 15.4% (+/- 9.1), 23.3% (+/- 10.1), and 14.4% (+/- 9.0) of the vessel diameter (p < 0.01). In addition, the diameter of capillaries increased (p < 0.01) and the capillary interspaces decreased (p < 0.01) after endothelin administration, but not in a linear dose-dependent manner. The dose of endothelin correlated with the change in the mean systemic (r = 0.82, p < 0.01) and the mean pulmonary (r = 0.80, p < 0.01) blood pressures. The mean pulmonary pressure change correlated with the focal venous contraction on the casts (r = 0.35, p < 0.01), capillary diameter (r = 0.64, p < 0.01), and capillary interspace distance (r = -0.34, p < 0.01). The venous contraction was related to the capillary diameter (r = 0.26, p < 0.01). The most notable effect of endothelin-1 in rat pulmonary microcirculation is focal constriction of small veins. Because this effect may lead to pulmonary edema, endothelin antagonists may be of benefit in a variety of clinical situations.
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PMID:Endothelin-1 focally constricts pulmonary veins in rats. 760 38

Endothelin-1 is a potent vasoconstricting substance that may aggravate circulatory dysfunction in acute myocardial infarction. In 59 patients with acute myocardial infarction peripheral venous blood was sampled, and endothelin-1 was measured by radioimmunoassay. Hemodynamic measurements were performed with a flow-directed thermodilution catheter in 16 patients. Plasma endothelin-1 levels in Killip's classes were as follows: group I (no heart failure, n = 25), 1.97 +/- 0.69 pg/ml; group II (heart failure, n = 16), 2.74 +/- 1.02 pg/ml; group III (pulmonary edema, n = 13), 4.54 +/- 1.17 pg/ml; and group IV (cardiogenic shock, n = 5), 8.91 +/- 3.16 pg/ml (normal control group, n = 12: 1.51 +/- 0.39 pg/ml). There were significant correlations between the plasma endothelin-1 level and mean right atrial pressure (r = 0.554; p < 0.05), mean pulmonary artery pressure (r = 0.589; p < 0.02), and cardiac index (r = -0.534; p < 0.05). There were closer correlations between plasma endothelin-1 level and mean pulmonary artery wedge pressure (r = 0.678; p < 0.005) and total pulmonary vascular resistance (r = 0.831; p < 0.001). These results indicate that endothelin-1 is elevated in accordance with cardiac and pulmonary circulatory distress in patients with acute myocardial infarction, which may further aggravate circulatory dysfunction.
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PMID:Plasma endothelin-1 in acute myocardial infarction with heart failure. 843 94

The intrathecal (i.t.) injection of endothelins to conscious rats was found to cause respiratory arrest. To gain some insights into this central phenomenon, peripheral vascular permeability and lung oedema were measured after i.t. and i.v. injections of these peptides. When injected at T-8 spinal cord level, endothelin-1 (65 and 650 pmol) and endothelin-3 (650 pmol) enhanced vascular permeability in the lungs by 22-fold and 7-fold, respectively, and caused sudden death at the highest dose. Less prominent increases (between 1.4- and 2.2-fold) of vascular permeability were observed in other tissues (trachea, kidney, ears, skin of hind paws and back skin) with endothelin-1. Endothelin-1 (650 pmol) caused a similar increase (27-fold) in lung vascular permeability when injected at T-2, although the response was significantly less (P < 0.05) if injected at the L-4 (15-fold) spinal cord level. Only endothelin-1 produced lung oedema when injected at the T-2 or T-8 level. In contrast, intravenous injection of endothelins-1 and -3 (650 pmol) did not produce lung oedema and the lung vascular permeability was increased by only 1.4-1.6-fold and all rats survived. The prior i.t. injection of 6.5 nmol BQ-123 (cyclo[D-Trp, D-Asp, L-Pro, D-Val, L-Leu]), a selective endothelin ET(A) receptor antagonist, prevented the increases of lung vascular permeability and oedema and the mortality induced by i.t. endothelin-1 (650 pmol). Whereas i.v. treatment with phentolamine (2 mg/kg) or pentolinium (25 mg/kg + 50 mg/kg per h x 15 min) abolished the lung vascular permeability changes evoked by endothelin-1 (650) pmol), atropine (1 mg/kg), NG-nitro-L-arginine (50 mg/kg) or indomethacin (5 mg/kg) had no effect. Moreover, the effects of endothelin-1 were attenuated in capsaicin pretreated rats (125 mg/kg, 10 days earlier) and almost abolished in rats subjected to sympathectomy with 6-hydroxydopamine (100 mg/kg, 24-48 h earlier). All these treatments except atropine and NG-nitro-L-arginine prevented the endothelin-1-induced lung oedema and reduced the lethality by around 50%. These results suggest that the increases of pulmonary vascular permeability and oedema induced by i.t. endothelin-1 are due to an intense pulmonary vasoconstriction mediated by alpha-adrenoceptors following the release of catecholamines in response to the activation of endothelin ET(A) receptor in the spinal cord. This central phenomenon seems to be reflexogenic, including the involvement of primary afferent C-fibers and spinal cord ascending fibers to the brain. Thus, endothelin-1 could play a role in neurogenic pulmonary oedema through a central mechanism.
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PMID:Increased pulmonary vascular permeability and oedema induced by intrathecally injected endothelins in rat. 960 Jun 61

Endothelin-1, (ET-1, EDN1) is an endogenous polypeptide which demonstrates dominant vasoconstriction activity and mitogenic effect. It has positive inotropic and chronotropic effects on the heart, stimulates the sympathetic and the renin-angiotensin-aldosterone systems and modifies homeostasis. The human ET-1 gene which consists of 6836 nucleotides located on chromosome 6p23-p24 produces Pre-pro-ET-1, which is consequently cleaved to big-ET-1. The mature 21-amino acid ET-1 is generated by subsequent enzymatic cleavage of the big-ET-1. A comprehensive review of the literature on the consequences of different ET-1 gene variants on ET-1 linked diseases has not been accomplished. Many variants of ET-1 gene, including transversion, transition, insertion, and repeated nucleotide polymorphisms, which influence the hereditary risk of cardiovascular and other related diseases have already been located, genotyped, and examined. Among them ten polymorphisms including transversion; -1370 (T-1370G) (rs1800541), +5665 (Lys198Asn) (rs5370), G2288T polymorphisms (rs2070699), and -974 C<A (rs3087459) polymorphism, transition; +3660 (Glu106Glu) (rs5369), G(8002)A (rs2071942), rs1476046 polymorphism , rs2071943 polymorphism, and rs9296345 polymorphism, and insertion/delete; +138 (+138/ex1ins/delA) (rs1800997) were studied and phenotyped extensively. Some significant associations with many different diseases (phenotypes) especially those related to cardiovascular system diseases such as hypertension, ischemic diseases, angina, and acute coronary syndrome have been described in the literature. Some are associated with other diseases such as asthma, pulmonary edema, hearing impairment, obesity and sleep apnea. Moreover, some are modifying the course and adverse effects of several drugs. Many of these polymorphisms were studied, thus some inner complex association manner was also described.
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PMID:Polymorphism in Endothelin-1 Gene: An Overview. 2739 91