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Query: UMLS:C0020538 (hypertension)
 170,190 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

As an experimental model, we used 6-week-old genetically obese-hypertensive rats (SHR-fa/fa) which were obtained by transferring the fatty/fa gene of hyperlipaemic obese rats into the genome of the SHR strain: the SHR-fa/fa were bigger and more hypertensive than their SHR littermates. Studying the capacity of the hearts, kidneys, spleens, brains and lungs to synthesize PGE2, PGF2 alpha and TXA2, enabled us to show that the hearts and lungs of SHR-fa/fa synthesized more PG than those of SHR; SHR-fa/fa brains generated less icosanoids than those of SHR; the amounts of PGE2 and TXA2 produced by the kidneys are similar in SHR and in SHR-fa/fa. From the experimental data we can infer that the introduction of the fatty/fa gene into the genome of SHR does not significantly alter the capacity of the kidneys to synthesize icosanoids; the more severe hypertension in the SHR-fa/fa would result from an increase in TXA2 biosynthesis by cardiac tissue which, at the same time, synthesized more PGE2, which could be a means of defence against hypertension. Moreover this genetical manipulation inhibited the icosanoid-synthesizing capacity of the brain which thus attenuated the central nervous system activity of the animals.
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PMID:Comparative study of the biosynthesis of PGE2, PGF2 alpha and TXA2 by different organs of genetically hypertensive (SHR) and obese-hypertensive (SHR-fa/fa) rats. 346 20

Plasma levels of thromboxane B2 (TXB2) and 6-keto-prostaglandin F1 alpha (6-keto-PGF1 alpha), stable metabolites of two prostanoids with opposing biological effects, TXA2 and prostacyclin, were measured by radioimmunoassay in normal pregnancy (controls) and pregnancy complicated by hypertension (PIH) from 32 to 36 (Period 1; P1) and from 36 to 40 (Period 2; P2) weeks of gestation. The plasma concentration of each compound in the control subjects was 265.6 +/- 58.4 (TXB2), 132.4 +/- 16.5 (6-keto-PGF1 alpha) for P1 (n = 10) and 142.6 +/- 11.8 (TXB2), 68.5 +/- 5.2 (6-keto-PGF1 alpha) for P2 (n = 10) respectively (pg/ml, mean +/- s.e). In the patients with PIH, TXB2 concentrations increased moderately for P1 (419.2 +/- 21.2; n = 7) and significantly (p less than 0.005) for P2 (452.8 +/- 31.0; n = 7) respectively (pg/ml, mean +/- s.e), while the plasma levels of 6-keto-PGF1 alpha revealed a slight to moderate decrease both for P1 (84.5 +/- 4.0; n = 7) and P2 (59.7 +/- 8.1; n = 7) respectively (pg/ml, mean +/- s.e). The physiological balance of TXB2 to 6-keto-PGF1 alpha was significantly greater (p less than 0.005) in the patients with PIH, where the TXB2/6-keto-PGF1 alpha ratio was 5.2 +/- 0.7 for P1 and 9.4 +/- 2.3 for P2 respectively (mean +/- s.e) compared with that of the controls, where it was 2.4 +/- 0.4 for P1 and 2.0 +/- 0.2 for P2 respectively (mean +/- s.e).(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Plasma thromboxane and prostacyclin: comparison during normal pregnancy and pregnancy complicated by hypertension. 353 Jul 28

The object of this study was to develop an assay for platelet activating factor (PAF) in rat plasma, and to utilise this to determine the effects of dietary fish oil on PAF in normotensive and spontaneously hypertensive rats. Measurement of platelet activating factor in blood plasma has proved difficult because of its rapid hydrolysis in vivo to lyso PAF. We describe here a method based on the prior acetylation of lyso PAF extracted from plasma to PAF before bioassay using 14C-serotonin labelled platelets. The active material found in acetylated plasma extracts was characterized as PAF by its chromatographic mobility, the action of phospholipases A2, C and D and by cross-desensitization studies with rabbit platelets. Rats fed dietary fish oil ('max EPA') had significantly decreased plasma lyso-PAF levels compared to control animals fed hydrogenated coconut oil (HCO). Serum thromboxane B2 (TXB2) levels were also significantly lower in animals fed the 'max EPA' diet. Spontaneously hypertensive rats (SHR) had significantly lower plasma lyso-PAF levels than their normotensive Wistar Kyoto (WKY) controls maintained on the same diets. It is proposed that dietary alterations in PAF synthesis may influence platelet behaviour in addition to the well described effects of dietary fish oil on the proaggregatory prostanoid TXA2. Rat strain differences in lyso-PAF synthesis occur, but are unlikely to be related to the maintenance of hypertension in SHR.
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PMID:Dietary fish oils reduce plasma levels of platelet activating factor precursor (lyso-PAF) in rats. 370 10

Thromboxane A2 (TXA2) is mainly formed in thrombocytes. It promotes thrombocyte aggregation and contracts the blood vessels. TXA2 appears to be a specific physiological thrombotic agent. Synthesis of TXA2 is elevated in patients with diabetes mellitus of types I and II and in hypertensive patients. TXA2 has a half-life of about 30 s under physiological conditions. Prostacyclin (PGI2) is formed in the vessel walls. Its action is antagonistic to TXA2, that is, it inhibits platelet aggregation and dilates the blood vessels. Synthesis of PGI2 is depressed in the presence of the classical 4 main risk factors for atherosclerosis: arterial hypertension, hyperlipoproteinaemia, smoking and diabetes mellitus. PGI2 has a half-life of about 3 min under physiological conditions. Since TXA2 and PGI2 are very labile and thus extremely difficult to measure, it is at present usual to measure their stable metabolites thromboxane B2 (TXB2) and 6-keto-prostaglandin F1 alpha (6-keto-PGF1 alpha). Radioimmunological measurement (RIA) of TXB2 in plasma requires no preliminary work, but radioimmunological measurement of 6-keto-PGF1 alpha in plasma requires prior extraction and concentrating, since the concentration of 6-keto-PGF1 alpha in the plasma is usually below the detection limit of commercial RIA kits. This paper describes standardized conditions for drawing the blood sample, a simple method of extraction from plasma, and the reliability of two commercial RIA kits with 125I tracer in measuring TXB2 and 6-keto-PGF1 alpha in plasma.
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PMID:Routine measurement of thromboxane B2 and the prostacyclin metabolite 6-keto-prostaglandin F1 alpha in plasma. 377 54

When CV-4151, a specific thromboxane (TX) A2 synthetase inhibitor, was given orally to 4 week old (4w) spontaneously hypertensive rats (SHR) daily for 3 weeks, the initiation of hypertension was delayed by about one week. The agent increased urinary excretion of water, sodium and creatinine, reduced that of TXA2 (as TXB2), increased that of PGI2 (as 6-keto-PGF1 alpha) and enhanced urinary PGI2/TXA2. In 4w Wistar-Kyoto rats (WKY) and 18w SHR was established hypertension, the agent had little effect on blood pressure and renal function. In isolated, perfused kidneys of 6w SHR, CV-4151 markedly inhibited both arachidonic acid-induced pressor action and production of TXA2. TXA2 synthetase activity in renal cortical microsomes of 5w SHR was approximately 1.5 times higher than that in age-matched WKY. CV-4151 inhibited TXA2 synthetase activity of medullary and cortical microsomes more effectively in 5w SHR than in age-matched WKY. Thus, in young SHR, the TXA2 synthetase inhibitor seemed to improve renal function by altering the balance of renal TXA2 and PGI2 biosynthesis and subsequently caused a delay in the initiation of hypertension. The present findings lend support to the idea that an imbalance in the renal TXA2-PGI2 biosynthesis may be involved in the initiation of hypertension in SHR.
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PMID:Delay of the initiation of hypertension in spontaneously hypertensive rats by CV-4151, a specific thromboxane A2 synthetase inhibitor. 392 75

As platelet and renal thromboxane (TX)A2 synthesis are increased in spontaneously hypertensive rats (SHR), we tested the hypothesis that increased renal TXA2 synthesis may cause the reduction in glomerular filtration rate (GFR), renal plasma flow (RPF), and the increase in arterial pressure in SHR of the Okamoto-Aoki strain. A selective inhibitor of TXA2 synthetase (UK 38485) was given acutely, with or without a TXA2 receptor antagonist (EP-092), to 6- to 8-wk-old SHR and age-matched Wistar-Kyoto rats (WKY) and chronically for 5.5 wk to 3.5-wk-old SHR. Inhibition of TXA2, measured by the stable metabolite TXB2, in the acute experiments was greater than 95% in serum and greater than 80% in glomeruli; in the chronic studies, it was greater than 65% in glomeruli. There was no endoperoxide shunting to vasodilatory and natriuretic prostaglandins (PGE2, PGI2) in glomeruli after TXA2 inhibition. Before drug administration, GFR and RPF were reduced and renal vascular resistance (RVR) was increased in SHR. During acute blockade of renal TXA2 synthesis, with or without a TXA2 receptor antagonist, there was no significant change in GFR, RPF, or RVR in WKY and SHR. Inhibition of TXA2 did not affect urine flow or sodium excretion in anesthetized or conscious WKY or SHR. Mean arterial pressure did not fall in treated SHR and WKY. Chronic TXA2 synthesis inhibition did not improve GFR or RPF in SHR, and systolic arterial pressure was not altered. These findings show that enhanced serum and glomerular TXA2 synthesis do not significantly contribute to the reduction in renal function and are not essential for the development of hypertension in young SHR.
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PMID:Role of thromboxane in control of arterial pressure and renal function in young spontaneously hypertensive rats. 395 27

1 The effects of acute pretreatment with the thromboxane synthetase inhibitor dazoxiben 5 mg/kg intravenously (UK 37248-01) were examined on the acute pulmonary responses of pentobarbitone-anaesthetized cats to E. coli endotoxin 2 mg/kg intravenously. 2 E. coli endotoxin in control, untreated, cats resulted in a marked pulmonary hypertension, an increase in intra-tracheal pressure (at a constant pulmonary inflation volume), an increase in both pulmonary arterial and aortic concentrations of thromboxane B2 (TXB2) and a reduction in systematic arterial PO2. 3 Dazoxiben prevented, or markedly reduced, the endotoxin-induced pulmonary release of TXB2, the decrease in systematic arterial PO2 and the pulmonary arterial hypertension, but did not modify the increase in intratracheal pressure. 4 These results may suggest that TXA2 is responsible for the endotoxin-induced pulmonary arterial hypertension but that some other arachidonic acid derivative (prostaglandin F2 alpha) is responsible for the reduced lung compliance that follows the acute administration of E. coli endotoxin.
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PMID:Effect of dazoxiben, a specific inhibitor of thromboxane synthetase, on acute pulmonary responses to E. coli endotoxin in anaesthetized cats. 633 3

To counter the paucity of documention on thromboembolic disorders caused by oral contraceptives (OC), a case study is presented describing the incidence of occlusion of arteria centralis retinae in a 24-year old woman after prolonged use of an OC, Bisecurin. She had taken Bisecurin for 4.5 years and had gained 20 kg during that time, but stopped usage 1 month before admission. She was hospitalized with severe deterioration of vision in the left eye. An eye examination indicated an edematous condition of the retina and reddening of the macula. Acuity of vision value for the left eye was .01 vs. 1.0 for the right, which was confirmed by fluorescein fundus angiography. Moderately decreased antithrombin III (AT III) activity was also ascertained. Treatment consisted of immediate retrobulbar injection with Tolazolin followed by Rheomacrodex, Cavinton infusions, B1 and B12 injections, Oradexon subconjunctival injection as well as vitamin B complex, Cavinton, and Colfarit tablets and a fat-free diet. Significant improvement of the left eye condition appeared 4 weeks later. Periodic follow-ups showed the healing of the condition around the macula; however, the patient suffered permanent damage to the retina due to the arterial occlusion above and below the macula. The disturbed lipid values of metabolism were also returned to normal, as borne out by normal dextrose loading results 8 months later (glucose tolerance was abnormal during examination at admission). The estrogen and progesterone components of OCs have been shown to reduce AT III levels, shorten heparin-thrombin coagulation time, increase fibrinogen levels, decrease HDL cholesterol levels, and produce excess TXA2 (thromboxan) resulting in vasoconstriction and thrombocyte aggregation. The risk of thrombosis is 6 times higher in OC users than in nonusers, although other susceptibility factors (obesity, diabetes, hypertension) also contribute to thrombosis.
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PMID:[Arterial occlusion in the ocular fundus induced by oral contraceptives]. 651 54

We examined the role of thromboxane in mediating the alterations in pulmonary hemodynamics and in lung fluid and protein exchange after thrombin. Studies were made in control sheep and in sheep pretreated with the thromboxane synthetase inhibitor, Dazoxiben (injection of 10 mg/kg followed by infusion of 4 mg/kg per hr). Thrombin infusion caused an increase in mixed venous and aortic concentrations of thromboxane B2, a stable degradation product of thromboxane A2, whereas the concentrations of 6-keto-PGF1 alpha, a degradation product of prostacyclin, did not change significantly. In sheep pretreated with Dazoxiben, thromboxane B2 concentrations did not increase, indicating effectiveness of the thromboxane synthetase inhibitor. The blood concentrations of 6-keto-PGF1 alpha after thrombin increased in the thromboxane synthetase-inhibited group, indicating shunting towards prostacyclin synthesis. Thrombin in untreated sheep increased pulmonary lymph flow (Qlym) and the lymph protein clearance (Qlym X lymph-to-plasma protein concentration ratio). The increases in lymph parameters were due to an increase in pulmonary vascular permeability to proteins because raising left atrial pressure further increased Qlym but did not change lymph-to-plasma ratio. Dazoxiben prevented the thrombin-induced increase in pulmonary vascular permeability because the increase in left atrial pressure resulted in an increase in Qlym and a decrease in lymph-to-plasma ratio, as was the case after left atrial hypertension in normal animals. Therefore, thrombin results in selective release of thromboxane A2 which precedes the increase in pulmonary vascular permeability. Thromboxane A2 may contribute to the increased permeability after thrombin, since inhibition of thromboxane synthesis prevents the permeability change.
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PMID:Thromboxane generation after thrombin. Protective effect of thromboxane synthetase inhibition on lung fluid balance. 668 1

It has been thought that blood vessels apart from the umbilical artery produce little or no thromboxane (TX) A2. However selective inhibitors of TXA2 biosynthesis have substantial effects on vessel physiology, suggesting that small amounts of TXA2 may be important in regulating function. This indirect evidence is now supported by direct measurements of TXB2 (the produce of TXA2 conversion) using both gas chromatography-mass spectrometry (GCMS) and radioimmunoassays. At least four independent laboratories have now demonstrated TXB2 production by various blood vessels. These studies suggest that vessel wall TXA2 is present in amounts more than adequate to exert biological actions on both vascular reactivity and on platelets. This may require re-evaluation and revision of present concepts of hypertension and thrombosis.
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PMID:Thromboxane A2 in blood vessel walls and its physiological significance: relevance to thrombosis and hypertension. 699 7


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