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

Endothelial cells are known to secrete various antiproliferative and vasodilating factors, such as nitric oxide and natriuretic peptides. The presence of endothelial dysfunction, well known in hypertensive individuals, potentially results in the development and progression of atherosclerosis. Therefore, it is important to know the factors that might influence endothelial cell growth. We examined the mitogenic actions of hepatocyte growth factor (HGF) on human endothelial and vascular smooth muscle cells. Exogenously added human recombinant HGF stimulated endothelial but not vascular smooth muscle cell growth in a dose-dependent manner. We also compared the mitogenic action of HGF with that of basic fibroblast growth factor and vascular endothelial growth factor. Interestingly, the mitogenic action of HGF on endothelial cells was greater than the actions of basic fibroblast growth factor and vascular endothelial growth factor, whereas basic fibroblast growth factor but not HGF and vascular endothelial growth factor stimulated vascular smooth muscle cell growth. Given the characteristics of HGF as an endothelium-specific growth factor, we evaluated the relationship of circulating HGF and blood pressure in normotensive and hypertensive subjects. Serum HGF concentration has been reported to be elevated in response to organ damage, such as in hepatitis and nephritis, and recent findings show that HGF may play an important role in tissue regeneration. We hypothesized that HGF might contribute to the protection or repair of vascular endothelial cells. If so, serum HGF level might be elevated in response to endothelial cell damage induced by hypertension. To test this hypothesis, we measured serum levels of HGF, lipoprotein(a), plasminogen activator inhibitor-1, tissue plasminogen activator, total cholesterol, and blood pressure in 41 normotensive and hypertensive subjects without liver, kidney, or lung damage. Serum HGF concentration was significantly correlated with systolic pressure (P < .01, r = .43) but not diastolic pressure. Serum HGF concentration in hypertensive subjects was significantly higher than in normotensive subjects. None of the other factors showed any correlation with blood pressure. We have demonstrated that HGF is an endothelium-specific growth factor whose serum concentration is significantly associated with systolic pressure. These results suggest that HGF secretion might be elevated in response to high blood pressure as a counterregulatory system against endothelial dysfunction.
Hypertension 1996 Sep
PMID:A vascular modulator, hepatocyte growth factor, is associated with systolic pressure. 879 25

Hemorrhagic transformation (HT) is a poorly understood yet frequent complication of stroke. A transient increase in blood pressure (BP) occurs immediately after experimental embolization in rabbits and we evaluated the relationship between this acute hypertensive response and subsequent hemorrhagic transformation, as well as the attenuation of this hypertensive response with an anesthetic dose of halothane. We also examined embolism-induced HT during infusion of the thrombolytic agents tissue plasminogen activator and streptokinase. A blood clot embolus was injected into the internal carotid artery and flushed into the middle cerebral artery. In the first experiment, BP was monitored in anesthetized or unanesthetized rabbits for 20 min prior to and up to 1 h after embolization. In the second experiment, animals were embolized half-way through an infusion of tPA (3.0 mg/kg; 20% administered as an iv bolus, with the remainder infused over 30 min) or streptokinase (30,000 U/kg iv infused over 30 min). In unanesthetized animals, the HT score (number of brain sections displaying visible HT) was significantly correlated with the peak mean arterial pressure recorded at embolization (r = 0.60, n = 24, P < 0.01). No relationship was observed between BP and HT score in animals anesthetized with halothane. Although HT incidence and extent were significantly related to elevated BP in the unanesthetized animals, halothane administration actually increased HT incidence. Embolization during thrombolytic infusion did not increase the occurrence or severity of HT. These data suggest that acute hypertension, but not ongoing thrombolysis, is a significant risk factor for HT following cerebral embolization.
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PMID:Acute hypertension, but not thrombolysis, increases the incidence and severity of hemorrhagic transformation following experimental stroke in rabbits. 879 66

The fibrinolytic and metabolic changes associated with doxazosin treatment were evaluated in 20 patients with mild to moderate hypertension. Steady-state plasma glucose (SSPG) concentration was used to subdivide hypertensive patients into two groups of 10 each: Insulin-resistant (SSPG > 190 mg/dl) and nonresistant (SSPG < 190 mg/dl). The blood pressure was normalized after 4 to 6 months of doxazosin treatment in both groups, but it was associated with significantly lower fasting plasma triglyceride level, lower integrated insulin response to a 75 gm oral glucose load, lower SSPG concentration, significant decreases in plasma plasminogen activator inhibitor type one antigen and activity and tissue plasminogen activator antigen, and a significant increase in tissue plasminogen activator activity only in the insulin-resistant group but not in the nonresistant group. It was also noted that the improvement of the fibrinolytic and metabolic abnormalities in the insulin-resistant group tended to return to the less abnormal levels seen in the non-resistant group. The data suggested that doxazosin treatment of hypertension attenuated much of the abnormalities of insulin resistance but had little effect on insulin-sensitive patients. It may support a link between impaired fibrinolysis and insulin resistance in patients with hypertension.
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PMID:Effect of doxazosin on fibrinolysis in hypertensive patients with and without insulin resistance. 883 67

Assessment of the risks of new antithrombotic therapies is best undertaken by evaluating risk factors for bleeding in individual patients, and risks associated with specific antithrombotic agents. This forms the basis for the development of a management strategy for major bleeding complications. Patient-related risk factors for bleeding with oral anticoagulants include: trauma, invasive procedures, history of bleeding disorder, high anticoagulant intensity, concomitant use of antiplatelet drugs, presence of underlying severe disease, advanced age, and prior history of cerebrovascular accident, or gastrointestinal bleeding. Weight-adjusted and other nomograms are more successful in achieving a balance between therapeutic effect and safety with intravenous heparin. The most important complication of thrombolytic therapy is intracranial haemorrhage, and the risks increase with age > 65 years, weight under 70 k, hypertension on admission and the use of tissue plasminogen activator: this profile is helpful in assessing risk-benefit ratio amongst individual patients. Recent experience with the experimental use of antithrombin agents such as hirudin, indicates a delicate dose-response relationship as it relates to the risk of cerebral haemorrhage, when used in conjunction with thrombolytic agents. A definitive answer regarding the role of hirudin and the balance of safety and efficacy awaits completion of ongoing trials. Novel IIb/IIIa platelet inhibitors appear to offer a significant therapeutic advance: major bleeding is variable and depends in part on the use of concomitant procedures, and heparin therapy. It is important to identify the source and severity of bleeding with the use of antithrombotic therapy and its haemodynamic consequences in constructing a management plan. Well developed treatment algorithms for patients with severe bleeding exist, and although laboratory testing may be helpful, it is on balance of marginal benefit since patients usually require urgent therapy. Future investigation promises more readily available, rapid and specific laboratory testing, and newer antithrombotic agents that are easier to administer and monitor. Molecular targeting with fusion proteins that attract to a specific antigen, thereby delivering more effective and safe therapy, offer new promise.
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PMID:Bleeding risks, risk factors and management of bleeding complications after treatment with anticoagulants, specific antithrombins, thrombolytics IIb-IIIa receptor blockers. 886 23

Thirteen patients with mild hypertension (untreated diastolic blood pressure of 95 to 114 mmHg) received, in random order, three successive treatments of four weeks with placebo, spirapril (6 mg daily), or hydrochlorothiazide (HCT2) (24 mg daily). At the end of each treatment, blood samples for assessment of platelet aggregation and platelet release of platelet factor 4 (PF4) and for assessment of fibrinolysis, estimated by tissue plasminogen activator (t-PA), plasminogen activator inhibitor-type 1 (PAI-1), and euglobulin clot lysis time (ECLT), were taken, first at rest, then immediately after five to ten minutes of vigorous exercise, and finally after the subsequent hour of recovery rest. Platelet aggregation induced in vitro by adrenaline significantly decreased during treatment with HCT2, the threshold rising to 10 microM as compared with 1.0 with placebo (P < 0.05) at rest, and the threshold for adenosine diphosphate (ADP) aggregation also rose, from 2 microM to 4 (NS). The resting plasma PF4 value fell, although not significantly, during HCT2 treatment from the placebo value of 3.28 to 2.56 ng/mL. During spirapril treatment there was no change in the threshold of either adrenaline or ADP for aggregation of platelets sampled at rest, and the PF4 plasma levels showed no significant reductions at rest. However, during exercise PF4 showed an approximate doubling of the resting value irrespective of therapy. This exercise-induced increase in PF4 was significantly reduced by spirapril as compared with placebo (P < 0.05). ECLT and t-PA did not shift significantly from the placebo level during either therapy. PAI-1 did not change during spirapril therapy, but during HCT2 treatment it fell, although not significantly, to 9.36 IU/mL from 15.91 with placebo (NS). Spirapril and HCT2 did not produce any unwanted side effect on platelet function or fibrinolysis. HCT2 seems to decrease platelet activity at rest, whereas spirapril seems to some extent to decrease platelet activity at exercise.
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PMID:Effect of spirapril and hydrochlorothiazide on platelet function and euglobulin clot lysis time in patients with mild hypertension. 887 80

In 31 patients with osteonecrosis (primarily of the hip), 74% had 1 or more primary coagulation disorders. In 18 patients, 15 (83%) who had coagulation disorders, the osteonecrosis was initially identified as idiopathic and was not associated with known underlying drugs (glucocorticoids) or diseases (alcoholism, sickle cell disease, Gaucher's disease). In 13 patients, 8 (62 %) who had coagulation disorders, the osteonecrosis was initially identified as secondary, and was associated with glucocorticoids in 12 patients, and with alcoholism in 1. The coagulation disorders included thrombhophilia (increased tendency to intravascular thrombosis) and hypofibrinolysis (reduced ability to lyse thrombi). Of the 18 patients initially thought to have idiopathic osteonecrosis, thrombophilia alone was found in 12% (resistance to activated protein C in 6%, low protein C in 6%), hypofibrinolysis alone was found in 50% (high lipoprotein(a) in 44%, low stimulated tissue plasminogen activator activity was found in 6%), and mixed thrombophilia hypofibrinolysis was found in 22%. Resistance to activated protein C was more common in these 18 patients than in healthy controls (11% versus 0%), as was high lipoprotein(a) (67% versus 20%). Of the 13 patients with secondary osteonecrosis, thrombophilia alone was found in 8% (low protein C), hypofibrinolysis alone was found in 30% (high Lp(a) in 15%, low tissue plasminogen activator activity in 15%), and mixed thrombophilia hypofibrinolysis was found in 23%. Low tissue plasminogen activator activity was more common in the 13 patients with secondary osteonecrosis than in controls (27% versus 7%), as was low protein C (23% versus 0%). In aggregate, these findings lead us to the speculation that primary, heritable thrombophilia or hypofibrinolysis causes thrombotic venous occlusion in the head of the femur, leading to venous hypertension and hypoxic death of bone (osteonecrosis).
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PMID:Thrombophilia and hypofibrinolysis: pathophysiologies of osteonecrosis. 900 95

Hypertension is associated with derangements in glucose and lipid metabolism. Increased levels of plasminogen activator inhibitor type 1 (PAI-1) are thought to potentiate the development of coronary events in this condition. Fish oil (omega3 polyunsaturated fatty acids [PUFAs]) have lipid-lowering effects, but the cardioprotective potential has been questioned because fish oil has been found to increase PAI-1 activity. This study was performed to determine the effects of omega3 PUFAs on the fibrinolytic function in hypertension. Seventy-eight persons with untreated hypertension were included in a 16-week, double-blind, randomized, controlled intervention study with 4 g/d of eicosapentaenoic and docosahexaenoic acids or corn oil placebo. Plasma PAI-1 activity, tissue plasminogen activator (tPA) activity, levels of fibrinogen and factor VII(c), and platelet count were measured before and after intervention (mean+/-SE). PAI-1 activity changed similarly in the fish oil and corn oil groups (1.8+/-1.0 U/mL versus 3.5+/-1.2 U/mL, P=.25), as did tPA (-0.02+/-0.02 IU/mL versus -0.13+/-0.03 IU/mL, P=.28), levels of factor VII(c) (6+/-5% versus 5+/-4%, P>.3), and platelet count (2+/-7x10(9)/L versus 3+/-5x10(9)/L, P>.3). None of these variables changed from pretreatment levels during fish oil intake. Fibrinogen levels increased significantly both during fish oil (0.6+/-0.1 g/L, P=.0001) and corn oil (0.4+/-0.1 g/L, P=.002) intake. There was no between-group difference (P>.3). In conclusion, a daily intake of 4 g omega3 PUFAs does not affect PAI-1 and tPA activity in persons with hypertension. A modest increase in fibrinogen levels was observed after both fish oil and corn oil intake.
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PMID:Fibrinolytic function after dietary supplementation with omega3 polyunsaturated fatty acids. 915 42

Stereotactic aspiration is well known for its simplicity and safety in the surgical treatment of hypertensive intracerebral hemorrhage. Postoperative fibrinolytic infusion with urokinase or recombinant tissue plasminogen activator and drainage of liquified hematoma are often used to improve the removal of hematoma. We evaluated the safety and effectiveness of streptokinase in this treatment modality in patients with hypertensive intracerebral hemorrhage or cerebellar hemorrhage. Twelve patients with hypertensive intracerebral hemorrhage underwent stereotactic aspiration using streptokinase as a fibrinolytic agent. There were six cases of putaminal hemorrhage, three of thalamic hemorrhage, and three of cerebellar hemorrhage. All but one patient had a large hematoma and presented with intracranial hypertension. Stereotactic aspiration was undertaken to remove the hematoma. Postoperatively, streptokinase was infused into the residual hematoma every 6 to 12 hours via a catheter implanted during the operation. Liquified hematoma was aspirated by syringe manually just before each infusion of streptokinase. The average duration of the entire treatment was 6 days (range 1-7). The residual hematoma at the end of treatment was less than 10 mL in all patients. Intracranial hypertension also subsided significantly in all patients. Only one patient had aspiration-induced bleeding during the operation. We conclude that stereotactic aspiration of hypertensive intracerebral hemorrhage is relatively safe and simple. Streptokinase can be infused intracerebrally to drain residual hematoma without severe side-effects.
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PMID:Combined use of stereotactic aspiration and intracerebral streptokinase infusion in the surgical treatment of hypertensive intracerebral hemorrhage. 944 15

Fibrinolytic therapy substantially reduces mortality from acute myocardial infarction. Patient selection is, however, important. The patient must present within 12 hours of the onset of ischaemic symptoms, have definite ECG changes of ST elevation or left bundle branch block and no contraindications. The major contraindications are those for risk of an intracerebral bleed, recent stroke, intracranial tumour or risk of a major systemic bleed. Age and hypertension are not contraindications but may modify the regimen used. Heparin is required with recombinant tissue plasminogen activator but is optional with streptokinase. The recent COBALT trial suggests that the accelerated weight related t-PA regimen given over 90 minutes is more satisfactory than double bolus t-PA. However, in patients under 75 years of age, the two regimens were equivalent. For patients suffering acute myocardial infarction, practitioners should now individualise choice of therapy, rather than give the same cocktail to all patients. The choice of regimen will depend on the cardiac risk, the stroke risk, the bleeding risk and the cost.
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PMID:The current status of thrombolytic therapy. 944 5

Abnormalities in fibrinolysis, endothelial function, and glucose and lipid metabolism have been reported in hypertension. This study was conducted to examine the interrelationships between fibrinolytic factors, glucose and lipid metabolism, and endothelial function in hypertension. The effects of administering an angiotensin converting enzyme inhibitor, benazepril, were also examined. Blood levels of the following substances were measured in patients with borderline and mild hypertension (n=50, 51+/-19 years) and in age-matched controls (n=10): total cholesterol, triglycerides, tissue plasminogen activator activity and antigen, and plasminogen activator inhibitor type 1 activity and antigen. Insulin sensitivity was assessed by oral glucose tolerance test, and endothelial function was assessed by evaluating changes in diameter of the brachial artery during reactive hyperemia as observed by ultrasonography. Activities of tissue plasminogen activator and plasminogen activator inhibitor type 1 were both elevated in the hypertensive patients. Stepwise multiple regression analysis showed that plasminogen activator inhibitor type 1 antigen correlated with insulin sensitivity, total cholesterol levels, and triglycerides levels (P<.01). Endothelial function was negatively correlated with tissue plasminogen activator activity and antigen (P<.01). The chronic administration of benazepril (5-10 mg/d) for 20 weeks improved insulin sensitivity, endothelial function (6.6+/-3.4-->9.0+/-2.5%, P<.01), and tissue plasminogen activator activity and antigen. These results indicate that abnormalities in fibrinolysis are associated with endothelial dysfunction as well as disorders of glucose and lipid metabolism in patients with borderline and mild hypertension. The treatment of such patients with benazepril appeared to improve the impairment in fibrinolysis and endothelial dysfunction.
Hypertension 1998 Jan
PMID:Relationship between endothelial function and fibrinolysis in early hypertension. 945 23


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