Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0729233 (Thoracic)
 6,478 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Thoracic and abdominal aortas were obtained from rats after irradiation and used for the estimation of the synthesis of prostacyclin (PGI2) determined as 6-keto PGF1 alpha. Twenty four h after exposure to 7.0 Gy an increase was noted in the amount of PGI2 released, and 4 weeks later its level significantly decreased. The 24 h value did not increase with the further radiation dose increment (9, 12.5, 15 Gy). Cysteine or H2O2 intensified prostacyclin synthesis in control vessels but decreased it in vessels from the animals irradiated 24 h earlier. Later after the exposure cysteine or H2O2 were no longer effective.
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PMID:Irradiation of rats abolishes susceptibility of PGI2 synthesis in blood vessels to peroxidative agents. 211 Oct 36

The aim of our study was to assess whether the development of chronic uremia in rats with extensive renal mass ablation was associated with an impairment of primary hemostasis as occurs in humans with terminal uremia. We also wanted to assess whether uremic rats had an increased generation of vascular prostacyclin (PGI2) and whether conjugated estrogens could influence such an abnormality. Our results showed that the development of chronic renal failure in rats was associated with a significant prolongation of bleeding time as reported in humans. Thoracic aorta and inferior vena cava specimens from uremic rats produced significantly more 6-keto-prostaglandin F1 alpha (the stable breakdown product of PGI2) than did specimens from the corresponding controls. Conjugated estrogens significantly shortened the bleeding time of uremic rats. The effect on bleeding time was detectable in the majority of animals within 4 hours from conjugated estrogen injection, reached its maximum at 24 hours, and returned to preinjection values within 72 hours from conjugated estrogen injection. Estrogen administration did not influence the generation of vascular PGI2. It is concluded that the model of extensive renal ablation in the rat is a suitable one to study changes in primary hemostasis in chronic renal failure and that the effect of estrogens on primary hemostasis in uremia is not mediated by changes in vascular PGI2.
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PMID:Prolonged bleeding time and increased vascular prostacyclin in rats with chronic renal failure: effects of conjugated estrogens. 284 17

The degree of mixing in fluid layers immediately adjacent to the endothelial surface is a major variable in assessment of prostacyclin (PGI2) production by cultured endothelial cells or intact vessel endothelium in vitro. Lack of adequate mixing should lead to underestimation of true production because PGI2 immediately adjacent to endothelium would be only poorly sampled upon buffer collection. Thoracic aortas from 38 New Zealand white rabbits were therefore excised, opened longitudinally, and mounted endothelial side uppermost in a buffer-filled chamber which excluded cut tissue edges from study. Production of PGI2 under unstirred and magnetically stirred conditions was measured by radioimmunoassay (RIA) for 6-keto-PGF1 alpha. For animals pretreated with the combination of papaverine and heparin (see below), unstimulated and arachidonate-stimulated 6-keto-PGF1 alpha increased with stirring rate toward limits of 2.9 and 28.5 ng/cm2/min, respectively. Unstimulated and stimulated 6-keto PGF1 alpha measured at 650 rpm, for example, were greater than their values at 0 rpm by factors of 3.5 (2P less than .01) and 3.7 (2P less than .001), respectively. The process of vessel excision, however, produces another variable: degree of injury to endothelium caused by such factors as secondary vessel contraction and thrombin generation. Vessel contraction and thrombin generation can be minimized, respectively, by the use of a smooth muscle relaxant and heparin administered prior to killing of the animals. The rabbits were, therefore, grouped according to intravenous (IV) treatment, prior to killing, with saline, papaverine (4 mg/kg), heparin (200 U/kg) or the combination of papaverine and heparin (same doses). As compared with pretreatment with saline, papaverine alone, or heparin alone, pretreatment with the combination of papaverine and saline led to increases in stimulated 6-keto-PGF1 alpha of 1.6- to 2.8-fold. By transmission electron microscopy, endothelium from animals pretreated with saline showed ultrastructural changes, including disruption of cytoplasm, separation without detachment of most endothelial cells from subendothelium, and focal areas of denudation. In contrast, ultrastructural integrity of endothelium was preserved in aortas of animals pretreated with combined papaverine and heparin. These results support the hypothesis that unstirred diffusional layers lead, in vitro, to underestimation of PGI2 production, especially when vessels are protected from excisional injury.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Prostacyclin production in vitro by rabbit aortic endothelium: correction for unstirred diffusional layers. 390 18

Contractile responses to prostacyclin (PGI2) as well as the generation of PGI2 "like-material" in isolated aorta from rabbits and rats, were studied. PGI2 produced a biphasic response on thoracic aorta isolated from rabbits and rats, i.e. vasodilatation at low concentrations and distinct contraction at higher ones. The rabbit aortic arch responded with relaxation in the presence of a wide range PGI2 concentration. Inhibitors of prostaglandins and thromboxane A2 (TXA2) biosynthesis such as corticosterone, indomethacin, acetylsalicyclic acid, imidazole and L-8027, abolished the stimulatory effect of PGI2 in the thoracic aorta from rats and rabbits, while alpha adrenoreceptor blockers failed to modify the vasoconstricting influence. The basal generation of PGI2 "like-material" by thoracic aorta was significantly higher in rats than in rabbits. Thoracic aortic strips from rabbits diminished the antiaggregatory capacity of 5 ng/ml of PGI2 during 40 sec and the effect disappears within 2 min. The foregoing results suggest that in thoracic aorta from rats and rabbits the vasoconstrictor effect of PGI2 could be evoked by the production of an unstable constricting prostanoid with aggregatory capacity, presumably TXA2.
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PMID:The stimulatory effect of prostacyclin (PGI2) on isolated rabbit and rat aorta is probably associated to the generation of a thromboxane A2 (TXA2) "like-material". 634 59

We have previously demonstrated altered platelet reactivity subsequent to splanchnic artery occlusion (SAO) shock in pigs: decreased reactivity, such as might be seen subsequent to submaximal stimulation, was observed in the postrelease period. Prostacyclin (PGI2) formed and released by vessel endothelium may function as a circulating hormone and regulate platelet reactivity by opposing the stimulatory influence of other factors. We have therefore investigated PGI2 release by aortas taken at "death" (systolic blood pressure = 30 mmHg) from pigs subjected to shock induced by a 2-hr occlusion of the superior mesenteric artery (SMAO). This shock is analogous to, but with a longer time course than, SAO shock. Aortas from sham-operated animals (matched for "death" time to the SMAO animals) served as controls. Thoracic aortas were removed, placed in cold 50 mM pH 7.5 tris buffer, cleaned of adhering tissue or clots, cut into rings and suspended in room temperature 50 mM pH 7.5 tris buffer into which PGI2 was released. Aliquots of the latter were quantitated for PGI2 by bioassay using human platelets for which a dose-response relationship for pure, synthetic PGI2 had been established: aliquot PGI2 quantities were determined graphically from the log dose-response (percentage inhibition of aggregation) curves, and converted arithmetically to amount per weight tissue. After 10 min incubation of tissue in buffer, the mean +/- SEM PGI2 for the shock animals (N = 8) was 0.053 +/- 0.02 ng/mg, and for the sham animals (N = 7), 0.174 +/- .06; the P value for t-test of means was 0.083. For 30-min incubation, the mean PGI2 for the shock group was 0.052 +/- 0.02 and for the sham, 0.283 +/- 0.11; the P value was 0.029. Inhibitory activity of the buffer aliquots declined in parallel with authentic PGI2. Thus, the occurrence of SMAO shock resulted in a significant decrease in aortic release of PGI2. Altered platelet reactivity as a consequence of shock, such as demonstrated by us and by others, could thus be in part a result of lowered endothelial release of PGI2, either alone or in combination with the occurrence of activation by other factors.
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PMID:Aortic prostacyclin release is lowered by superior mesenteric artery occlusion (SMAO) shock in pigs. 702 34

Primary pulmonary hypertension (PPH) is a progressive disease characterised by raised pulmonary vascular resistance, which results in diminished right-heart function due to increased right ventricular afterload. PPH occurs most commonly in young and middle-aged women; mean survival from onset of symptoms is 2-3 years. The aetiology of PPH is unknown, although familial disease accounts for roughly 10% of cases, which suggests a genetic predisposition. Current theories on pathogenesis focus on abnormalities in interaction between endothelial and smooth-muscle cells. Endothelia-cell injury may result in an imbalance in endothelium-derived mediators, favouring vasoconstriction. Defects in ion-channel activity in smooth-muscle cells in the pulmonary artery may contribute to vasoconstriction and vascular proliferation. Diagnostic testing primarily excludes secondary causes. Catheterisation is necessary to assess haemodynamics and to evaluate vasoreactivity during acute drug challenge. Decrease in pulmonary vascular resistance in response to acute vasodilator challenge occurs in about 30% of patients, and predicts a good response to chronic therapy with oral calcium-channel blockers. For patients unresponsive during acute testing, continuous intravenous epoprostenol (prostacyclin, PGI2) improves haemodynamics and exercise tolerance, and prolongs survival in severe PPH (NYHA functional class III-IV). Thoracic transplantation is reserved for patients who fail medical therapy. We review the progress made in diagnosis and treatment of PPH over the past 20 years.
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PMID:Primary pulmonary hypertension. 972 4