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)

We cultured smooth muscle cells from rat renal preglomerular arterioles by injecting a suspension of iron oxide into the left ventricle, separating the arterioles magnetically, and growing cells from explants. In passaged cultures we ascertained vascular smooth muscle purity of > 98% by morphology; contraction to norepinephrine and angiotensin; positive immunofluorescence staining through the sixth passage with monoclonal antibodies to smooth muscle-specific alpha- and gamma-isoactins, myosin, and desmin; and the absence of von Willebrand factor. Angiotensin II (10(-12)-10(-5) M) induced dose-dependent DNA synthesis and proliferation of subcultured (three times) arteriolar smooth muscle cells from a growth-arrested state (p < 0.01). Angiotensin II (10(-5) M) also induced the cells to express c-fos mRNA. We find no previous report of culture of smooth muscle cells from renal preglomerular arterioles. Our findings also provide evidence that angiotensin II is mitogenic to arteriolar muscle cells and thus may be involved in their hyperplasia accompanying hypertension.
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PMID:Culture of renal arteriolar smooth muscle cells. Mitogenic responses to angiotensin II. 139 76

Two murine monoclonal antibodies, raised against von Willebrand factor (vWF), were used to construct an enzyme-linked immunosorbent assay (ELISA), for quantitation of vWF antigen (vWFAg) in human plasma and platelets. This assay had a lower limit of sensitivity of 0.0001 IU/ml in buffer, and thus is one to two orders of magnitude more sensitive than other ELISA assays which have been reported. The intraassay, interassay and interdilution coefficients of variation were 4.1, 10.4 and 9.9%, respectively. In normal plasma (n = 20), the vWFAg level was 0.83 (range: 0.42-1.25) IU/ml. In normal washed platelets (n = 10), 0.35 (0.25-0.49) IU/10(9) platelets was found. In plasma obtained from various patient groups the following vWFAg levels (geometric mean and range) were observed: von Willebrand's disease (n = 19): 0.18 (0.02-0.77) IU/ml; patients with liver cirrhosis (n = 20): 3.73 (1.68-9.20) IU/ml; patients with pregnancy-induced hypertension (n = 20): 4.14 (2.28-7.44) IU/ml and patients with malignant disease (n = 10), 2.54 (1.51-5.60) IU/ml. A linear correlation was found between vWFAg levels measured with a polyclonal antibody based Laurell electroimmunoassay (r = 0.92, n = 58) or with a polyclonal antibody based ELISA (r = 0.94, n = 64). The present assay is based on stable and reproducible reagents and allows the specific measurement of vWFAg in plasma and in platelets. This assay may constitute a useful tool for the further investigation of clinical conditions associated with changes in vWFAg levels. In addition, its high sensitivity may facilitate a more detailed study of platelet vWFAg in normal and in pathological conditions.
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PMID:Measurement of von Willebrand factor antigen in plasma and platelets with an enzyme-linked immunosorbent assay based on two murine monoclonal antibodies. 177 82

In case-control study of 53 cases of intracerebral hemorrhage diagnosed by CT scan. Significant risk factors were chronic alcoholism (P less than 0.05), history of hypertension, fundus arteriosclerosis, aorta atherosclerosis, electrocardiogram (ECG) abnormalities, high blood triglycerides, hyperviscosity, hyper-plasma viscosity, hyperfibrinogenemia and increased VWF (P less than 0.01 or P less than 0.001). After principal component analysis hyperviscosity, hypertension, coronary heart disease, ECG abnormalities, chronic alcoholism, and increased VWF were selected as primary risk factors (accumulative contributed rates 59.84%). Alcoholism, EXG abnormalities, aorta atherosclerosis correlates significantly with haemorheology.
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PMID:[Risk factors of intracerebral hemorrhage. A case-control study]. 180 64

Microangiopathy and disseminated platelet aggregation have been reported in thrombotic thrombocytopenic purpura (TTP) and pregnancy-induced hypertension (PIH). Since unusually large von Willebrand factor (vWF) multimers have been implicated in the evolvement of TTP, we analyzed factor VIII/vWF parameters in patients with PIH. Mean vWF: Ag level was significantly higher in 27 patients with PIH as compared to 20 matched healthy pregnant women (358 +/- 160 u/dl vs. 274 +/- 125 u/dl. p less than 0.05). Moreover, plasma vWF: Ag levels and the ratio of vWF: Ag to factor VIII were found to be linearly correlated to the severity of PIH. In contrast, no significant differences in mean levels of factor VIII and ristocetin cofactor were observed between these groups. Crossed immunoelectrophoresis of vWF revealed a higher incidence of a pre-peak and an increased migration index in the PIH group as compared to the control group (60% vs. 44% and 1.27 +/- 0.26 vs. 1.19 +/- 0.18, p less than 0.01 respectively). Analysis of plasma vWF multimer patterns by 1.4% agarose electrophoresis in 0.1% SDS revealed excessive amounts of large, medium and small size multimers in the PIH patients. Conceivably, the quantitative changes in vWF multimers reflect endothelial injury and may play a role in the microangiopathy observed in PIH.
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PMID:von Willebrand factor multimer patterns in pregnancy-induced hypertension. 251 Mar 50

In primary pulmonary hypertension of recent clinical onset, pulmonary endothelial cells show injury. To characterize this phenomenon, we measured plasma von Willebrand factor (vWF) by immunologic and ristocetin cofactor assays in 6 patients with primary pulmonary hypertension, 17 patients with secondary pulmonary artery hypertension associated with congenital heart disease or cystic fibrosis, and 13 patients with congenital heart disease and normal pulmonary artery pressure. In selected cases, we also determined the vWF multimer pattern. In all 6 cases of primary pulmonary hypertension, the ristocetin cofactor activity was increased relative to the vWF antigen (vWF:Ag) concentration (a ratio of 2.55 +/- 0.36; normal range, 0.8 to 1.4); 4 of the 6 also had a similar and abnormal vWF multimer pattern--an increased proportion of the fastest moving bands. In the other 2, the multimer pattern was normal. Of the other 30 patients, a mild increase in ristocetin cofactor/vWF:Ag was seen in only 2 with secondary pulmonary hypertension and 1 with normal pulmonary artery pressure: these also had an abnormal vWF multimer pattern that was different from that observed in patients with primary pulmonary hypertension. The vWF abnormalities we describe in primary pulmonary hypertension offer a marker of the disease and could be helpful in understanding its pathogenesis.
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PMID:von Willebrand factor abnormalities in primary pulmonary hypertension. 310 58

In eight male patients with normal liver and kidney function fibrinolytic components were measured in arterial blood and in renal and hepatic vein blood, obtained during catheterization for analysis of hypertension. Blood samples were collected simultaneously from veins und corresponding arteries before and 5 minutes after the completion of intravenous injection of desmopressin (DDAVP), 0.4 micrograms/kg body weight over a 10 minute period. DDAVP induced a rise in t-PA antigen and activity, and in von Willebrand factor, accompanied by a decrease in free PA-inhibitor level. We failed to detect a significant rise in plasma urokinase activity. The concentrations of fibrinogen, plasminogen, alpha 2-antiplasmin, antithrombin III and coeruloplasmin did not change either. Renal production of t-PA under basal conditions was inferred from a negative arterio-venous (A-V) difference in t-PA-activity and in t-PA-antigen levels but this could not be confirmed by orthogonal regression analysis of the same data. A-V differences of other fibrinolytic factors were negligible. In the hepatic vessels a significant positive A-V difference of t-PA-activity and of t-PA-antigen levels was a uniform finding. After DDAVP, when plasma levels were elevated, the mean A-V difference was proportionally higher, consistent with a constant fractional elimination rate. Free PA-inhibitor was virtually absent from arterial blood after DDAVP, but appeared in hepatic vein blood, indicating either production of the inhibitor by the liver or dissociation of a circulating complex of t-PA and its inhibitor in the liver. The blood levels of the other investigated components did not show any change upon passage through the liver.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Renal and hepatic handling of endogenous tissue-type plasminogen activator (t-PA) and its inhibitor in man. 314 78

PARD is a prospective study sponsored by the German Research Council with the aim to establish if spontaneously enhanced platelet aggregation or changes of other hemostatic variables are risk factors for new vascular occlusions in diabetic patients. 363 diabetics (aged 45-65, 232 men, 131 women) have been observed for at least 5 years. Of the 232 men, 53 were on diet, 104 on oral antidiabetic agents and 75 on insulin. Of 131 women 16 were on diet, 46 on oral antidiabetic drugs and 69 on insulin. At entry a medical history was obtained and clinical examinations and laboratory tests were performed. Hemostatic tests and clinical examinations were repeated at 3 month's intervals. The life status was followed for all patients with the exception of 2. Until December 31, 1984, 42 patients had died, 23 from cardiovascular disease and 19 from other causes. 13 patients suffered a myocardial infarction, 11 a stroke and 53 a peripheral arterial occlusion. The occurrence of new vascular occlusions was significantly higher in men with enhanced spontaneous platelet aggregation measured by PAT III. This was not the case for women. Other hemostatic parameters with some relation to cardiovascular complications, again only in men, were fibrinogen, von Willebrand factor together with some established risk factors as triglycerides and hypertension.
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PMID:Haemostasiological parameters as risk factor for new arterial occlusions in diabetics. 349 Dec 49

Although lipids have received most attention in relation to atherosclerosis, vessel injury also has a role in the development of atherosclerotic lesions. Thrombi that form at sites of injury can be incorporated into the wall, causing thickening, and platelets that adhere to damaged vessel walls release a growth factor (PDGF) that stimulates smooth muscle cell proliferation. The early lesions of atherosclerosis are focal and develop around vessel orifices and branches in relation to the patterns of blood flow and areas of increased permeability and endothelial cell damage. Platelets also contribute to the complications of advanced atherosclerosis caused by occlusive thrombi, thromboembolism, and spasm. The causes of vessel wall injury are not established, although there is evidence pointing to disturbed blood flow, hypertension, antigen--antibody complexes, complement, materials originating from platelets and white blood cells, bacteria, endotoxin, viruses, smoking, dietary lipids, homocystinemia, diabetes, other metabolic disorders, and stress. Platelets do not adhere to intact endothelium, but they adhere to the constituents of the subendothelium, release the contents of their granules (including PDGF), and form thromboxanes. If blood flow is disturbed, platelet--fibrin thrombi can form at sites of injury. Platelet adherence to a damaged wall does not require von Willebrand factor except under conditions of high wall shear. Repeated injury of a vessel wall leads to the development of lipid-rich atherosclerotic lesions, even in normocholesterolemic animals, but these lesions do not form if the experimental animals are made thrombocytopenic before injury is induced. Measurable changes in platelets that are associated with the clinical complications of atherosclerosis include shortened survival, release of granule contents (platelet factor 4, beta-thromboglobulin, thrombospondin), formation of thromboxanes, and decreased buoyant density. "Antiplatelet drugs" such as aspirin are proving to be beneficial in selected groups of patients, such as those with unstable angina. Thromboxane synthetase inhibitors and agents that block the thromboxane receptor on platelets are under investigation. Long term administration of "antiplatelet drugs" to affect the rate of development of atherosclerosis seems neither feasible nor desirable. Modification of dietary and smoking habits and control of hypertension are more likely to be beneficial for most individuals.
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PMID:The role of platelets in the development and complications of atherosclerosis. 351 36

A microangiopathic syndrome was observed in 3 of 14 (21%) patients receiving cyclosporine and methylprednisolone (CSA-MP) for graft-versus-host disease (GVHD) prophylaxis between January 1991 and June 1992 at our center. The syndrome consisted of neurological abnormalities, arterial hypertension, intravascular hemolysis with red cell fragmentation, and a drop in platelet counts after allogeneic bone marrow transplantation (BMT) for hematological malignancy, and it occurred around day 50 after BMT. Treatment with plasma exchanges against fresh-frozen plasma resulted in a decrease of serum lactate dehydrogenase and an improvement of neurological symptoms. We compared CSA-MP patients retrospectively with patients who had received cyclosporine and methotrexate (CSA-MTX) for GVHD prophylaxis (n = 70) at our institution. All patients in both groups engrafted. Day 100 survival (80% vs. 79%) and transplant-related mortality (16% vs. 14%) were identical in the two groups. CSA-MP patients had significantly more acute GVHD II-IV (57% vs. 17%, P < 0.01). Arterial hypertension (P < 0.01) and neurological symptoms (P < 0.01) were significantly more frequent in the CSA-MP group. The 11 asymptomatic CSA-MP patients had significantly higher lactate dehydrogenase levels (P < 0.01) and lower platelet counts (P < 0.01) at 40, 60, and 100 days after BMT, which suggests the presence of a subclinical form of microangiopathy. Significantly higher plasma levels of von Willebrand factor antigen in CSA-MP patients on day 50 after BMT (P < 0.05) and absence of large von Willebrand factor multimers on gel electrophoresis in 4 of 13 (31%) CSA-MP patients compared with 0 of 14 (0%) CSA-MTX patients (P < 0.01) further suggest profound endothelial damage in patients receiving CSA-MP for GVHD prophylaxis.
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PMID:Microangiopathy following allogeneic marrow transplantation. Association with cyclosporine and methylprednisolone for graft-versus-host disease prophylaxis. 749 99

Patients with Type 2 (non-insulin dependent) diabetes mellitus are at increased risk of thrombosis and the premature development of atherosclerosis. This may be related to damage to the endothelium (which may be the primary target tissue for the disease process) resulting from a loss of normal glycaemic metabolic control. Thus changes in endothelial cell function, such as modified release of soluble leukocyte and platelet adhesion molecules, may be important. Accordingly, E-selectin, von Willebrand factor (vWf), vascular cell adhesion molecule (VCAM) and intercellular adhesion molecule (ICAM) were measured in serum from 60 patients and 76 controls. Raised levels of vWf (p = 0.0002), E-selectin (p < 0.0001) and VCAM (p = 0.003) in patient's samples failed to correlate with glycaemic control as assessed by levels of fructosamine and glycated haemoglobin, or with 24 h urine albumin. Levels of ICAM were not increased in our patients. Levels of the two endothelial cell products, vWf and E-selectin, failed to correlate although E-selectin correlated with low density lipoprotein cholesterol (p = 0.016). vWf correlated with VCAM (p < 0.001) and hypertension (p = 0.032). We conclude that levels of soluble adhesion molecules vWf, E-selectin and VCAM are raised in Type 2 diabetes mellitus. The mechanisms for these changes appear to be independent of glycaemic control but may relate to concurrent hypertension and/or hypercholesterolaemia.
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PMID:Increased levels of soluble adhesion molecules in type 2 (non-insulin dependent) diabetes mellitus are independent of glycaemic control. 753 16


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