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)

Experiments were designed to study endothelium-dependent responses in salt-sensitive (DS) and salt-resistant Dahl rats (DR). The rats were fed a low sodium (0.1% NaCl) or high sodium (8% NaCl) diet for 8 weeks. Blood pressure in DS fed a high sodium diet was higher than that in the remaining animals. Aortic rings with and without endothelium were suspended for isometric tension recording. Acetylcholine, adenosine 5'-diphosphate, and thrombin induced endothelium-dependent relaxations that were significantly depressed in the aorta of DS fed a high sodium diet. The relaxations in response to sodium nitroprusside were only slightly, but significantly, depressed in DS fed a high sodium diet. Removal of the endothelium greatly enhanced the response to serotonin and norepinephrine. In rings with, but not without, endothelium taken from rats fed a high sodium diet, the tension developed in response to serotonin and norepinephrine was significantly greater than that in animals fed a low sodium diet. These experiments indicate that endothelium-dependent relaxations to acetylcholine, adenosine 5'-diphosphate, and thrombin are depressed in hypertensive Dahl rats; this effect probably reflects a decreased release of endothelium-derived relaxing factor(s), although structural changes might contribute; and the responsiveness to vasoconstrictor agents is increased in DS and DR fed a high sodium diet. These findings may indicate differential effects of blood pressure and dietary salt on endothelial function.
Hypertension 1987 Feb
PMID:Endothelium-dependent vascular responses in normotensive and hypertensive Dahl rats. 381 12

Intracellular free calcium, [Ca2+]i, was studied in platelets of essential hypertensive subjects and normotensive controls under basal conditions and after stimulation with epinephrine, norepinephrine, angiotensin II, ouabain, and thrombin, using the fluorescent calcium indicator quin 2. Basal [Ca2+]i was significantly higher in hypertensive subjects (n = 32) than in normotensive controls (n = 30; 167.4 +/- 5.0 vs 143.2 +/- 3.1 nmol/L; p less than 0.001). Epinephrine, norepinephrine, angiotensin II, and ouabain had no effect on platelet calcium, whereas thrombin induced a dose-dependent increase in [Ca2+]i in both the presence and absence of extracellular calcium. This [Ca2+]i increase in the presence of extracellular calcium, which depends mainly on calcium influx, was significantly higher (p less than 0.05) in platelets of hypertensive subjects at all thrombin concentrations (ranging from 0.025-0.1 U/ml), while the [Ca2+]i increase in the absence of extracellular calcium, which depends only on release from intracellular stores, was similar in hypertensive subjects and controls. These results suggest that, in essential hypertension, there is not only increased platelet resting [Ca2+]i but also an increase in agonist-mediated calcium influx, which appears to indicate a cell membrane abnormality in the platelets of subjects with essential hypertension.
Hypertension 1987 Mar
PMID:Increased basal and thrombin-induced free calcium in platelets of essential hypertensive patients. 381 20

Monoclonal antibodies to purified human urinary kallikrein have been developed. Selection of antibody producing clones was based on 125I-kallikrein binding activity of hybridoma media in both radioimmunoassay and enzyme-linked immunosorbent assay. Three clones (2 IgG1, 1 IgG2b) were subcloned, characterized, and compared with the polyclonal antiserum generated in rabbits immunized with the purified kallikrein. With radioimmunoassay, mouse ascitic fluids or rabbit antisera dilutions showing 50% binding to 125I-kallikrein were 1:1.2 X 10(6) (E7A9), 1:1.2 X 10(5) (H6A6), 1:8.0 X 10(4) (E12H1), and 1:1.4 X 10(6) (the rabbit antisera). With enzyme-linked immunosorbent assay, mouse ascitic fluids from clones E7A9 and H6A6 showed half-maximal absorbance at dilutions of 1:2.1 X 10(5) and 1:1.0 X 10(5) respectively, and the polyclonal antiserum showed half-maximal absorbance at a dilution of 1:2.0 X 10(4). These monoclonal antibodies showed no cross-reactivity with rat tissue kallikrein, rat urinary plasminogen activator, or dog pancreatic kallikrein, while the polyclonal antiserum showed some cross-reactivity. The binding of monoclonal or polyclonal antibodies to 125I-human urinary kallikrein was not affected by human plasma kallikrein, thrombin, or urokinase in a competitive radioimmunoassay. By using purified human urinary kallikrein immobilized to agarose, antibodies produced by clones E7A9 and H6A6 and in the rabbit antisera were purified to homogeneity. Each of these affinity-purified antibodies inhibited the esterase activity, and two of the three inhibited the kininogenase activity, of human urinary kallikrein. A sandwich immunosorbent assay was developed to measure this kallikrein using monoclonal antibody from the clone E7A9 in conjunction with the polyclonal antibodies.(ABSTRACT TRUNCATED AT 250 WORDS)
Hypertension
PMID:Characterization of monoclonal and polyclonal antibodies to human tissue kallikrein. 385 80

Sensitivity to adrenaline-antagonism of the inhibitory effect of PGI2 on thrombin-induced increase in [Ca2+]i was measured in platelets from normotensive and untreated hypertensive subjects. Platelets from hypertensive subjects exhibited an increased sensitivity to adrenaline. This effect was more pronounced in younger patients with hypertension, and suggests an increased adenylate cyclase sensitivity in the early hypertension. The data also indicate that a mechanism linked to calcium-influx plays an important role in older hypertensives. This may explain the greater efficacy of calcium entry blockers in older hypertensive patients with essential hypertension.
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PMID:Hormonal modulation of intracellular free calcium in platelets from normotensive and hypertensive subjects. 388 86

Aggregation and secretion of washed platelets from stroke-prone spontaneously hypertensive rats (SHRSP) were greatly reduced by the development of the hypertension compared with those of platelets from age-matched normotensive Wistar-Kyoto rats (WKY). Concomitantly, thrombin-induced phosphorylation of the 47 kDa protein in SHRSP platelets was significantly decreased. However, TPA-induced aggregation, secretion and 47 kDa protein phosphorylation in SHRSP platelets were similar to those in WKY platelets. These results suggest that protein kinase C activity and its substrate were normally present in SHRSP platelets and that defects in the receptor-mediated activation of protein kinase C. This defective protein phosphorylation may be an underlying mechanism for the dysfunction of SHRSP platelets.
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PMID:Defects of thrombin-induced protein phosphorylation in platelets from stroke-prone spontaneously hypertensive rats. 394 26

Increased plasma levels of beta-thromboglobulin (beta TG) and fibrinopeptide A (FPA), markers of platelet release and thrombin generation respectively, were measured in normal women, women taking oral contraceptives, normal pregnancy and pregnant women with hypertension or pre-eclampsia. No significant increases in beta TG or FPA were found in women taking oral contraceptives. Significantly increased concentrations of beta TG, but not FPA, were found in normal pregnant women in the second and third trimester of pregnancy when compared with non-pregnant age-matched controls. In eleven women with pregnancy hypertension and thirteen women with pre-eclampsia significantly elevated levels of both beta TG and FPA were found when compared with age, parity and gestation-matched pregnant controls. Although the mean value for both beta TG and FPA in the group with pre-eclampsia was higher than the group with pregnancy hypertension, the difference was not statistically significant. These findings provide additional evidence that pre-eclampsia and pregnancy hypertension are associated with activation of the coagulation system and the platelet release reaction.
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PMID:Plasma fibrinopeptide A and beta-thromboglobulin in pre-eclampsia and pregnancy hypertension. 617 42

By activating plasminogen into plasmin, which in turn dissolves fibrin, fibrinolytic agents can dissolve pathologic thrombi. Streptokinase, a fibrinolytic agent derived from group C beta-hemolytic streptococci, is antigenic and can elicit allergic reactions. Urikinase, a fibrinolytic agent obtained by purification from human urine or from human fetal kidney cell culture, is not antigenic, and for this reason can be used repeatedly, if needed, whereas streptokinase cannot be used for retreatment within six months of a course of therapy. Either agent can be introduced into the circulation systemically (intravenously) or locally (via catheter). The indications for systemic therapy include deep-vein thrombosis, pulmonary embolism, and arterial thrombosis and embolism. The indications for local therapy include acute myocardial infarction, arterial thrombosis and embolism, and the clearing of occluded arteriovenous cannulae and access shunts. Contraindications include an actively bleeding lesion, a vascular intracranial disorder, or uncontrolled hypertension; relative contraindications include pregnancy; a recent wound, fracture, surgery, or deep closed biopsy; or a general contraindication to anticoagulation, such as coagulopathy, uremia, or severe liver disease. During thrombolytic therapy, invasive procedures, intramuscular injections, and the use of other anticoagulant or antiplatelet agents should be avoided. Measurement of fibrinogen levels, the titer of fibrin/fibrinogen degradation product, or thrombin time can be used to monitor therapy.
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PMID:Fibrinolysis and its current usage. 634 82

In 12 patients with arterial hypertension (stages I and II according to WHO), adrenergic stimulation was induced by the immersion of a hand in ice water for 2 min. Blood samples were withdrawn before, at the end of, and 15 min after the cold application: the experiment was repeated 2 h after the ingestion of 200 mg acebutolol, a selective betablocking agent. The following assays were performed: serum nonesterified fatty acid (NEFA), plasma beta-thromboglobulin (BTG) and PF4 with specific radioimmunoassays; thromboxane B2 (TXB2) in plasma was also estimated with radioimmunoassay, platelet sensitivity to exogenous prostacyclin; furthermore, the thrombin-induced thromboxane production before and after acebutolol ingestion as well as serum TXB2-levels were measured. The blood pressure and the heart rate were also monitored. After cold stimulation, a significant increase of NEFA, BTG, and plasma TXB2 was observed, which was still discernible 15 min after the application of cold. After acebutolol, the cold treatment led to a lower increase of blood pressure with a reduction of the heart rate, as well as to a diminished release of BTG, PF4 and TXB2 no changes in the reduced platelet sensitivity to prostacyclin were noticed.
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PMID:Platelet activation after adrenergic stimulation in hypertensive patients: effects of acebutolol. 635 66

That adrenaline is involved in the pathophysiology of essential hypertension (EHT) is suggested by the observed elevation of plasma adrenaline concentration in some patients. Adrenaline, by stimulating the alpha-2 adrenoceptor, causes vasoconstriction in the smooth muscle cell and initiates shape change and aggregation in platelets. Therefore, the effect of adrenaline on intracellular free calcium concentration ([Ca2+]i) in the platelets of hypertensive subjects was investigated as a model for vascular smooth muscle. Platelets from untreated patients with EHT had an elevated [Ca2+]i and incubation with adrenaline for 30 min caused a greater increase in [Ca2+]i in treated patients with EHT than in normotensive controls. This long-term effect of adrenaline was possibly linked to a defective calcium extrusion mechanism in hypertension. No immediate effect was observed on [Ca2+]i by PGI2 and adrenaline, while both modulated [Ca2+]i if the platelets were stimulated with thrombin. PGI2 prevented the thrombin-induced increase in [Ca2+]i and adrenaline antagonized the effect of PGI2. Platelets from untreated patients with EHT exhibited an increased sensitivity to thrombin and adrenaline when compared to normotensive and treated hypertensive subjects. It is suggested that these supersensitivities are related to the elevated [Ca2+]i in untreated hypertensive patients.
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PMID:Free calcium response to adrenaline in platelets of normal and hypertensive (untreated and treated) subjects. 640 Mar 64

The aggregation properties of washed SHRSP platelets were investigated in comparison with normotensive WKY platelets at prehypertensive (4 weeks), early hypertensive (11 weeks) and late hypertensive (17 weeks) ages in the absence of plasma factors. The number of platelets in SHRSP was markedly lower with the development of hypertension than that in WKY. The thrombin- and collagen-induced aggregation was markedly reduced in the platelets from 11 and 17 week old SHRSP compared with that of age-matched WKY, whereas the degree of platelet aggregation in 4 week old SHRSP showed a tendency to be even greater than that in WKY. The changes in blood pressure and platelet aggregability were correlated inversely. ADP did not induce aggregation in the same system used for thrombin and collagen stimulation but in another system it aggregated washed rat platelets. Aggregation responses to ADP and ionophore A23187 were also significantly lower in 14 week old SHRSP platelets than age-matched WKY platelets. Together with other evidence, these results suggest that defective Ca2+ function, rather than the presence of exhausted platelets, is responsible for hypoaggregability in SHRSP platelets.
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PMID:Hypoaggregability of washed platelets from stroke-prone spontaneously hypertensive rats (SHRSP). 642 Sep 47


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