Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0020538 (hypertension)
 170,190 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

In pregnant stroke-prone spontaneously hypertensive rats, salt-loading causes symptoms similar to those of human preeclampsia, such as hypertension and proteinuria. To seek evidence of the therapeutic potential in preeclampsia of antithrombin III (AT III), which is a serine protease inhibitor active on various enzymes of the coagulation cascade, we examined the effect of consecutive treatment with AT III on hypertension and proteinuria in this animal model. Salt-loading (2% NaCl diet) caused a significant elevation of systolic blood pressure on day 15-17 and of urinary protein excretion on day 17-19 of gestation, as compared with animals fed a normal diet. AT III, administered i.v. at a dose of 60 or 300 U/kg/d for 10 d from day 9-11 to 18-20, attenuated these pathological changes in a dose-dependent manner. Histological examination of the kidney revealed that AT III prevented the occurrence of arteriosclerosis and thickening of the capillary basement membrane. However, the pathological changes induced by salt-loading were not attributable to activation of the blood coagulation system. These results demonstrate that AT III has preventive action against salt-induced hypertension and proteinuria in pregnancy through a mechanism largely independent of its anticoagulant action. AT III may thus be beneficial for the treatment of clinical symptoms of preeclampsia.
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PMID:Antithrombin III prevents blood pressure elevation and proteinuria induced by high salt intake in pregnant stroke-prone spontaneously hypertensive rats. 879 79

We tested the hypothesis that enhanced intravascular coagulation in pregnancy could produce clinical symptoms similar to those of preeclampsia, such as hypertension, proteinuria, and edema. Having confirmed this, we then examined whether the pathological changes caused by intravascular coagulation could be suppressed by administration of antithrombin III (AT III), an endogenous inhibitor active to thrombin and factor X a. Intravascular coagulation was induced in Wistar rats on day 16-20 of pregnancy by 1-h arterial infusion of tissue thromboplastin (TP) through the left ventricle of the heart. One hour after the end of the infusion period, organ blood flows were measured by the radioactive ((57)Co-labeled) microsphere method, and fibrin deposition in organs was measured by radiolabeling with [(125)I] fibrinogen injected before TP infusion. Infusion of TP produced fibrin deposition in the kidney, lung, and liver, but not in the myometrium and placenta, as well as an 80% decrease in renal blood flow (RBF), with oliguria and proteinuria. TP also caused an increase in blood pressure (BP) accompanied by an increase in plasma renin activity (PRA), both of which were suppressed by bilateral nephrectomy before TP infusion. The prophylactic administration of AT III concentrates (60 or 300 U/kg intravenously (i.v.), followed by infusion of 30 or 150 U/kg/2 h, respectively) prevented all pathological changes in a dose-dependent manner. AT III increased placental blood flow regardless of the state of coagulation. These findings suggest that intravascular coagulation plays a significant part in the pathophysiology of preeclampsia and that AT III concentrates may have therapeutic potential in the treatment of this condition.
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PMID:Antithrombin III prevents renal dysfunction and hypertension induced by enhanced intravascular coagulation in pregnant rats: pharmacological confirmation of the benefits of treatment with antithrombin III in preeclampsia. 885 41

We correlated coagulation and fibrinolytic parameters with small-vessel disease revealed by magnetic resonance imaging (MRI) of the brain. One hundred and eleven patients with asymptomatic or symptomatic cerebral infarction were randomly selected for the study; 57 males and 54 females with an average age of 66.6 +/- 9.6, age range 40 to 85, years old. Among them, 76 patients had a history of symptomatic cerebral infarction; 38 patients hypertension; and 24 patients diabetes mellitus. Patients with large cortical infarction, cerebral hemorrhage, demyelinating disease or mass lesions were excluded from the present study. The MRI scans were reviewed for areas with increased signal intensity on T2-weighted images. The small infarction was defined as a lesion less than 10mm in diameter. The activity of von Willebrand factor (vWF) correlated significantly with the grade of caps at the anterior and posterior horns of the lateral ventricle, and the number of small infarctions in the subcortical white matter and basal ganglia, suggesting vWF could be a predictor for these small-vessel disease. The grade of caps at posterior horn of the lateral ventricle and the number of small infarctions in the subcortical white matter were associated significantly with the concentration of plasma fibrinogen and reversely with the activity of antithrombin III, an inhibitory factor in coagulation system. These results indicate that hypercoagulable state may causatively relate with small-vessel disease in the territory of medullary artery branching from cortical artery. On the contrary, these coagulation parameters did not correlate significantly with small ischemic lesions in the territory of perforating artery. No correlation was observed between the level of marker proteins for platelet activation and the degree of small-vessel disease, indicating the activation of platelet could not associate with the etiology of small-vessel disease.
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PMID:[Coagulation and fibrinolytic parameters as predictors for small-vessel disease revealed by magnetic resonance imaging of the brain]. 890 82

In the UK, the Committee for Safety of Medicines (CSM) issued a warning in October 1995 about the possible increased risk of nonfatal deep venous thrombosis (DVT) among users of oral contraceptives (OCs) containing the third generation progestogens, desogestrel and gestodene. Subsequent media coverage increased the number of consultations and enquiries about these OCs. CSM had concluded that, overall, the third generation OCs are safe. CSM recommended their continued use. Nevertheless, many women stopped using them and induced abortions increased by 11%. In April 1996, the Committee for Proprietary Medicinal Products issued a more cautious statement about the OCs and called for further evaluation. Chance, confounding, and bias may account for the increased risk observed in the studies in question. Yet, it is possible that these OCs may increase the risk of DVT. The increased risk may be offset by a reduced risk of acute myocardial infarction. Physicians need to conduct careful and thorough counseling and to allow the patient to be involved and to take responsibility in making a decision about OC use. They should document all counseling with a note that the patient understands and accepts the increased risk of DVT. They should not prescribe the third generation OCs to women with any of the absolute contraindications to OC use (ischemic heart disease, hypertension, atherogenic lipid disorders, focal or crescendo migraine, cigarette smoking, transient ischemic attacks, past cerebral/subarachnoid hemorrhage, history of vascular thrombosis, prothrombotic abnormalities [e.g., Factor V Leiden], conditions predisposing to thrombosis [e.g., systemic lupus erythematosus], and obesity. Women who are intolerant of second generation OCs may prefer third generation OCs. Physicians should selectively screen women with a family history of a first-degree relative younger than 45 with thromboembolism for Factor V Leiden. They should also screen for protein C, protein S, and antithrombin III deficiency and for acquired antiphospholipid antibodies.
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PMID:Oral contraceptives and the risk of DVT. 898 64

Mild hyperhomocysteinemia has been identified as a risk factor for arterial disease and for venous thrombosis. Individuals homozygous for the thermolabile variant of the methylene tetrahydrofolate reductase gene (MTHFR) which results from a common mutation Ala677-->Val and is found in 5-15% of the general population, have significantly elevated plasma homocysteine levels and may account for one of the genetic risk factors in vascular disease. We have analyzed the prevalence of MTHFR-T homozygotes in patients with arterial disease or venous thrombosis. We studied 191 patients with arterial disease and 127 individuals with venous thrombosis and compared with 296 unmatched controls. The results showed that there was a high prevalence of homozygotes for the mutated MTHFR-T allele among a group of patients with arterial disease (19%) in the absence of hyperlipoproteinemia, hypertension, and diabetes mellitus when compared to controls (4%), odds ratio of 5.52 (95% C.I., 2.27 to 13.51). The prevalence of homozygotes among patients with venous thrombosis was 11%, odds ratio of 2l93 (95% C.I., 1.23 to 7.01). The risk of venous thrombosis remained high, odds ratio of 2.63, even after we excluded 27 patients with hereditary thrombophilia (e.g. factor V Leiden, dysfibrinogenemia, deficiency of protein C, protein S, antithrombin III, or factor XII) from the 127 overall cases with venous thrombosis. These data support the hypothesis that being a homozygote for the MTHFR-T is a risk factor for the development of arterial disease and also for venous thrombosis.
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PMID:The mutation Ala677-->Val in the methylene tetrahydrofolate reductase gene: a risk factor for arterial disease and venous thrombosis. 918 84

We report a 57-year-old woman with optic-spinal form of active multiple sclerosis, who developed a large lobar type hemorrhage of the brain. She initially suffered from left visual loss, and three month later, she was hospitalized with paraplegia and total sensory loss up to the fourth thoracic level accompanied by sphincteric disturbance. Diagnosis of clinically probable multiple sclerosis was based on the relapsing-remitting clinical course and laboratory findings. Five months after admission, she developed sudden consciousness loss. Brain CT scan showed a massive hemorrhage in the right frontal to parietal lobe. The patient had no risk factors for cerebral hemorrhage including hypertension. Histopathological study of brain tissues obtained at surgical evacuation of hematoma did not reveal any malignancy, and congo-red staining of this specimen was negative. We analyzed coagulation, fibrinolytic, and endothelial parameters during the follow-up period. von Willebrand factor (vWF) as a marker for endothelial damages was elevated persistently. Moreover, thrombin-antithrombin III complex (TAT) as a marker for activation of coagulation was also elevated constantly throughout the clinical course. The findings suggest that fragility of the vascular walls and permeability changes associated with immunological mechanisms might have resulted in the cerebral hemorrhage. Although there are few reports of cerebral hemorrhage in patients with multiple sclerosis, it has been reported that vascular wall damage is an important aspect of the pathology of multiple sclerosis and acute cerebral vascular damage may sometimes occur in multiple sclerosis. We propose that coagulation studies including the endothelial marker such as vWF would provide a useful information regarding the risk of cerebrovascular complication in multiple sclerosis.
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PMID:[A case of optic-spinal form of multiple sclerosis with lobar type large cerebral hemorrhage]. 939 61

Preoperative acquired clotting parameters such as prothrombin time, activated partial thromboplastin time, antithrombin III, platelet concentration, and fibrinogen show coagulopathy caused by insufficiency of the diseased liver. Intraoperative determination of clotting factors or parameters is not helpful to direct intraoperative transfusion of blood, blood components, or platelets because transfusions performed solely for correction of clotting data do not correlate with the real intraoperative requirements and increase the costs of orthotopic liver transplantation. However, the use of antihyperfibrinolytic drugs seems to reduce intraoperative blood loss. Patients with cirrhotic disorders caused by portalvenous hypertension show extensive collaterals and increased intravascular blood volume. Thus it is plausible that especially overcorrection of blood loss during the surgical preparation in the preanhepatic phase of the operation results in extensive blood loss. Therefore, to avoid blood loss we attempt to keep volume substitution to a minimum during the preanhepatic phase of the operation. In contrast, during the anhepatic and postanhepatic phases we attempt to reestablish normovolemia by transfusing red packed blood cells and fresh-frozen plasma. Strictly confined use of blood products in the preanhepatic phase, followed by later correction of intravascular blood volume, may reduce intraoperative blood loss; it also seems to ensure adequate substitution of clotting factors.
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PMID:Coagulation techniques are not important in directing blood product transfusion during liver transplantation. 940 72

The present study evaluated the short-term effects of percutaneous 17 beta-estradiol on blood pressure, metabolic profile and hormonal levels in postmenopausal women with systemic arterial hypertension. After a wash-out period of 15 days, 10 hypertensive patients were treated with guanabenz acetate to control blood pressure, followed by 17 beta-estradiol in the form of hydroalcoholic gel administered for 21 of 28 days of each cycle, for 3 cycles. Patients were evaluated before, during and 2 months after estrogen administration. Systolic and diastolic blood pressure or heart rate did not present any significant change in any patient when compared to those periods with the antihypertensive drug only (pretreatment period and 60 days after estrogen therapy was discontinued). Plasma biological markers of hepatic estrogenic action (plasma renin activity, antithrombin III, triglycerides, total cholesterol and lipoproteins) also remained unchanged during the study. Hormone treatment was effective, as indicated by the relief of menopausal symptoms, a decrease in FSH levels (73.48 +/- 27.21 to 35.09 +/- 20.44 IU/l, P < 0.05), and an increase in estradiol levels (15.06 +/- 8.76 to 78.7 +/- 44.6 pg/ml, P < 0.05). There was no effect on LH (18.0 +/- 9.5 to 14.05 +/- 8.28 IU/l). Hormone levels returned to previous values after estrogen treatment was discontinued. The data indicate that short-term percutaneous 17 beta-estradiol replacement therapy, at the dose used, seems to be a safe hormone therapy for hypertensive menopausal women. Nevertheless, a controlled, prospective, randomized clinical assay with a larger number of subjects is needed to definitely establish both the beneficial and harmful effects of hormone replacement therapy in hypertensive women.
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PMID:Percutaneous 17 beta-estradiol replacement therapy in hypertensive postmenopausal women. 945 63

The dynamics of level of natural antibodies to catecholamines (adrenaline, noradrenaline and dopamine) and factors of blood coagulation system (thrombin, antithrombin III and alpha 2-macroglobulin) in 122 patients with hypertension and obesity was studied in hyposodium antiatherosclerotic diet and this diet enriched with phospholipid preparation "Vitol" during 4 weeks. Universal normalizing effect of the diet consists in increase of levels of natural antibodies to adrenaline, noradrenaline, dopamine, thrombin, antithrombin III and alpha 2-macroglobulin was found. The influence of the diet was more expressed during it enrichment by "Vitol".
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PMID:[Dynamics of the natural antibody level as affected by the biologically active food supplement "Vitol" in patients with hypertensive disease and obesity]. 1019 63

The vascular endothelium influences not only the three classically interacting components of hemostasis: the vessel, the blood platelets and the clotting and fibrinolytic systems of plasma, but also the natural sequelae: inflammation and tissue repair. Two principal modes of endothelial behaviour may be differentiated, best defined as an anti- and a prothrombotic state. Under physiological conditions endothelium mediates vascular dilatation (formation of NO, PGI2, adenosine, hyperpolarizing factor), prevents platelet adhesion and activation (production of adenosine, NO and PGI2, removal of ADP), blocks thrombin formation (tissue factor pathway inhibitor, activation of protein C via thrombomodulin, activation of antithrombin III) and mitigates fibrin deposition (t- and scuplasminogen activator production). Adhesion and transmigration of inflammatory leukocytes are attenuated, e.g. by NO and IL-10, and oxygen radicals are efficiently scavenged (urate, NO, glutathione, SOD). When the endothelium is physically disrupted or functionally perturbed by postischemic reperfusion, acute and chronic inflammation, atherosclerosis, diabetes and chronic arterial hypertension, then completely opposing actions pertain. This prothrombotic, proinflammatory state is characterised by vaso-constriction, platelet and leukocyte activation and adhesion (externalization, expression and upregulation of von Willebrand factor, platelet activating factor, P-selectin, ICAM-1, IL-8, MCP-1, TNF alpha, etc.), promotion of thrombin formation, coagulation and fibrin deposition at the vascular wall (expression of tissue factor, PAI-1, phosphatidyl serine, etc.) and, in platelet-leukocyte coaggregates, additional inflammatory interactions via attachment of platelet CD40-ligand to endothelial, monocyte and B-cell CD40. Since thrombin formation and inflammatory stimulation set the stage for later tissue repair, complete abolition of such endothelial responses cannot be the goal of clinical interventions aimed at limiting procoagulatory, prothrombotic actions of a dysfunctional vascular endothelium.
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PMID:Endothelial function and hemostasis. 1079 71


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