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

Tissue plasminogen activator (t-PA) is expressed by hypothalamic and peripheral sympathetic neurons. The sympathetic axons that permeate artery walls have not been investigated as possible sources of intramural t-PA. The plasmin produced by such a system would locally activate both fibrinolysis and matrix metalloproteinases that regulate arterial collagen turnover. To assess this neural t-PA production, we investigated the capacity of rat cervical sympathetic ganglion neurons to synthesize and release t-PA, and the expression of the enzyme in carotid artery and the iris-choroid microvascular tissues that receive the ganglion axon distribution. Functional studies confirmed that (i) the ganglion neuron cell bodies synthesize t-PA mRNA, (ii) cultured ganglion carotid artery and iris-choroid microvascular explants predominantly release t-PA rather than urokinase, (iii) microvascular tissues release approximately 20 times more t-PA per milligram than carotid explants (which accords with the higher innervation density of small vessels), and (iv) removal of the endothelium did not cause major reductions in the t-PA release from carotid and microvascular explants. Immunolocalization studies then confirmed a strong expression of the enzyme within the ganglion axons, the carotid adventitia that receives these axons, and the predominantly sympathetic axon terminals in the iris-choroid microvasculature. These data indicate the existence of a previously undescribed system for the delivery of neural t-PA to vessel walls. The intramural production of plasmin induced by this system represents a novel principle for the regulation of arterial matrix flexibility, especially in the media of densely innervated small arteries and resistance arterioles involved in the pathogenesis of stroke, hypertension, and vascular aging. Thus, the data suggest an important new interface between neuroscience and vascular biology that merits further exploration.
 ...
PMID:Functional and morphologic evidence of the presence of tissue-plasminogen activator in vascular nerves: implications for a neurologic control of vessel wall fibrinolysis and rigidity. 971 Feb 64

This study was designed to investigate the alterations in the levels of various proteases such as angiotensin converting enzyme (ACE), kallikrein, aminopeptidases, urokinase and plasmin in serum-heart and kidney and to find out whether the changes in the levels of these enzymes could explain the pathogeneses of hypertension induced by Dexamethasone (Dex). Dex was administered to Male Wistar rats (180-200 g body weight) at a dosage of 2.5 mg/kg/week subcutaneously on alternate days for 2 weeks. One more week was included in this investigation to oversee the recovery process. Mean Arterial Pressure (MAP) showed significant elevation during administration and after withdrawal of Dex. The levels of enzymes such as angiotensin converting enzyme, carboxypeptidase-N and leucine aminopeptidase were found to be elevated in serum as well as in tissues. The level of kallikrein was observed to decrease in serum and tissues and that of thrombin, plasmin and urokinase exhibited variations. Thus, treatment with Dex altered the levels of these proteases which might have a role in the pathogenesis of hypertension and in altered blood coagulation.
 ...
PMID:Dexamethasone induced alterations in the levels of proteases involved in blood pressure homeostasis and blood coagulation in rats. 1048 40

Three patients presenting with massive venous pulmonary thrombo-embolism are described, who have been selected from a series of 22 patients treated with thrombolysis during a 6-year period. A 23-year-old female presented with tachycardia and dyspnoea. She had pulmonary angiography following scintigraphy with a perfusion deficit of more than 60%. Thrombolysis resulted in open blood vessels and a disappearance of the complaints. A 51-year-old woman presented with profound hypoxemia, probably due to a patent foramen ovale, with shunting and tachycardia. Perfusion defects on scintigraphy combined with a normal chest radiograph in the absence of pre-existent pulmonary disease established the diagnosis. She responded favourably to intravenous streptokinase. The third patient was an 80-year-old woman with hypertension. She developed dyspnoea, tachycardia and shock following immobilisation due to a fractured hip. Despite an initial improvement on streptokinase, she deteriorated and died from right-sided heart failure. The diagnostic tests should be limited and aimed at ruling out left-sided heart failure and pericardial tamponade. Echocardiography is often diagnostic in these patients. Thrombolysis may be life saving but there are no randomised trials to prove that survival rate is indeed better compared to heparin therapy. Streptokinase is less expensive than alteplase and there is no evidence from trials to suggest that it is inferior to more expensive thrombolytics such as alteplase or urokinase.
 ...
PMID:[Three patients with massive pulmonary embolism]. 1199 57

To elucidate potential mechanisms of enhanced type 2 matrix metalloprotease levels and activity within the thickened aged rat aorta, the present study measured its mRNA and protein levels and those of its membrane bound activator, MT1-MMP, its endogenous tissue inhibitor, TIMP-2, tissue type, and urokinase plasminogen activators and their receptors, and an inhibitor of plasminogen activation in aortae from Fisher 344X Brown Norway rats, 2 to 30 months of age. Semiquantitative immunohistochemistry, in situ hybridization, and in situ zymography of aortae detected a marked age-associated increase in gelatinolytic activity of type 2 metalloprotease within the thickened intima, internal elastic lamina, and elastic fibers in the inner part of the thickened tunica media, whereas the intimal tissue inhibitor of metalloprotease-2 mRNA and protein levels were not age related. Both activators of plasminogen and their receptors increased approximately 2-fold within the intima between 2 to 30 months. Similar, but not identical, age-associated changes in factors that regulate protease activity within the aortic media were also observed. We conclude that discordant regulation of factors that determine the activation status of type 2 matrix metalloprotease, coupled with an increase in the expression of its zymogen, occur with aging, which lead to an increase in the amount of activated protease. These factors are candidate mechanisms for age-associated vascular remodeling, a potent risk factor for vascular diseases with advancing age.
Hypertension 2002 Apr
PMID:Altered regulation of matrix metalloproteinase-2 in aortic remodeling during aging. 1196 41

Life-threatening, complete middle cerebral artery infarction occurs in up to 10% of all stroke patients. The "malignant media occlusion" is an infarction occupying more than 50% of middle cerebral artery territory. The malignant, space-occupying supratentorial ischemic stroke is characterised by a mortality rate of up to 80%. Several reports indicate, that hemicraniectomy in this situation can be life-saving. Hemicraniectomy increases cerebral perfusion pressure and optimises retrograde perfusion via the leptomeningeal collateral vessels. A case of a patient is presented, having progressive neurological deterioration due to massive cerebral infarctions. The patient rehabilitation was successful. Decompressive surgery is life saving and can also give acceptable functional recovery. Hemorrhagic stroke is due to stroke in 15% of cases and in 10%, it is "spontaneous" intracerebral hematoma. The intracerebral and intraventricular hemorrhage represents one of the most devastating types of stroke associated with high morbidity and mortality. The 30-day mortality rate is 35% to 50% and most survivors are left with a neurological disability. The value of surgical therapy is debatable. The aspiration and urokinase therapy of the hematoma of intracerebral hemorrhage could improve final neurological outcome. Spontaneous, nontraumatic intraventricular hemorrhage frequently carries a grave prognosis. A large part of morbidity after intraventricular hemorrhage is related to intracranial hypertension from hydrocephalus. One patient presented had intracerebral hemorrhage and another had intraventricular hemorrhage treated with urokinase. Rapid and extensive reduction in the amount of intracerebral and intraventricular blood occurred. Urokinase lysis is safe and can be a potentially beneficial intervention in intracerebral and intraventricular hemorrhage. By performing decompressive craniectomy, the neurologists of stroke departments and intensive care units with the neurosurgeons will have to play major role in the management of stroke patients.
 ...
PMID:[New methods of intensive therapy in stroke: hemicraniectomy in patients with complete middle cerebral artery infarction and treatment of intracerebral and intraventricular hemorrhage with urokinase]. 1212 81

Chronic renal allograft rejection is often associated with the presence of fibrin thrombi in the microcirculation. Our purpose was to evaluate the influence of chronic rejection on fibrinolytic regulators in plasma of renal allograft recipients. We evaluated the concentration and activities of tPA, uPA and PAI-I in plasma from kidney allograft recipients. We studied 64 patients who underwent kidney transplantation from cadaveric allograft donors. At the time of the study 38 patients had stable graft function for at least 6 months proceeding the study, and 26 recipients had biopsy-proven chronic rejection of the kidney transplant. Control group included 30 healthy blood donors. In kidney transplant recipients we found significantly higher plasma tPA activity (median: 0.99 IU/ml; range: 0-3.8 IU/ml) in comparison to healthy controls (median: 0.15 IU/ml; range: 0-2.8 IU/ml) (p = 0.002) as well as significantly lower plasma PAI-I activity (median: 7.06 U/ml; range: 0-33.2 U/ml) in comparison to healthy controls (median: 21.8 U/ml; range: 0-36.7 U/ml), (p = 0.0001). Among transplant recipients, PAI-I plasma activity in recipients with chronic graft rejection (median: 10.16 U/ml; range: 0-33.2 U/ml) was significantly higher than in patients with stable graft function (median: 4.83 U/ml; range: 0-22.9 U/ml), (p = 0.01). In transplant recipients with stable graft function and poorly controlled hypertension we found significantly higher PAI-I plasma activity in comparison to recipients with normal blood pressure (p = 0.006). In kidney transplant recipients there was a positive correlation between the dose of prednisone and PAI-I activity in plasma (p = 0.01) and an association between BMI value and plasma PAI-I activity (p = 0.008), as well as an association between BMI value and plasma tPA-Ant concentration (p = 0.006). Among transplant recipients, patients treated with ACE inhibitors had significantly lower uPA plasma activity than the rest of the group (p = 0.003). In recipients with stable graft function we found a correlation between CsA concentration and tPA activity (p = 0.04), as well as an association between the dose of CsA and uPA-Ant concentration in plasma (p = 0.049). In patients with chronic graft rejection we found a negative correlation between the dose of prednisone and uPA-Ant plasma level (p = 0.004). Renal allograft recipients have higher tPA and lower PAI-I activities in plasma in comparison to healthy individuals. Chronic allograft rejection, is as well as poorly controlled hypertension, seem to be associated with an increase PAI-I plasma activity. In kidney graft recipients there is a relation between the value of BMI and the activity and concentration of tPA-Ant as well as the value of BMI and the PAI-I activity in plasma. Poorly controlled hypertension is associated with an increase in PAI-I plasma activity. The results of our study suggest a stimulatory effect of CsA on tPA and PAI-I plasma activities as well as on uPA-Ant concentration, while prednisone in turn seems to enhance PAI-I activity in plasma and decrease uPA expression. In renal allograft recipients ACE inhibitors seem to reduce uPA plasma activity.
 ...
PMID:The effect of chronic allograft rejection on plasma regulators of fibrinolysis. 1222 3

Understanding the importance and physiologic activity of the plasma kallikrein/kinin system (KKS) has been thwarted by the absence of an inclusive theory for its assembly and activation. The contact activation hypothesis describes the assembly and activation of this system in test tubes and disease states, but not under physiologic circumstances. Recent investigations have indicated a new cohesive hypothesis for understanding physiologic activation of this system. Prekallikrein (PK) and factor XI (FXI) through high molecular weight kininogen (HK) assemble on a co-localized, multiprotein receptor complex on endothelial cells that consists of at least cytokeratin 1 (CKI), gClqR, and urokinase plasminogen activator receptor (muPAR). When assembled on these proteins, prekallikrein becomes activated to kallikrein by the membrane-expressed enzyme prolylcarboxypeptidase (PRCP). Formed kallikrein then activates factor XII (FXII) for amplification of its activation and single chain urokinase. The plasma kallikrein/kinin system may serve as a physiologic counterbalance to the plasma renin angiotensin system (RAS) by lowering blood pressure and preventing thrombosis. Insights into the integrated role of these two systems may afford the development of novel therapeutic drugs to manage hypertension and thrombosis.
 ...
PMID:Assembly and activation of the plasma kallikrein/kinin system: a new interpretation. 1248 98

Acute myocardial infarction is a very rare event during pregnancy and bears the problem of misdiagnosis. However, about 150 cases have been published worldwide with a preponderance of anterior wall infarcts. With more women delaying childbearing until an older age and increasing prevalence of smoking in young women, it can be expected that all forms of coronary artery disease--including acute myocardial infarction--will be seen more often in the future. Among the causes of coronary artery occlusion in pregnancy are (1) rupture of very small coronary artery plaques triggered by different events, e.g., hypertension; (2) plain coronary artery disease; (3) dissection of coronary arteries; (4) coronary artery spasms with/without arterial thrombosis. Prompt diagnosis and immediate therapy are necessary to lower the high mortality of mother and fetus. The gold standard in the therapy of acute myocardial infarction during pregnancy is immediate coronary angiography and percutaneous transluminal coronary angioplasty (PTCA) with or without stent implantation. Application of thrombolytics (recombinant tissue plasminogen activator [rt-PA], r-PA, streptokinase [SK], urokinase [UK]) has been reported in single patients but should be limited to cases where acute PTCA is not available and where the infarct occurs before the 14th week of pregnancy because of possible embryopathy. If the patient is in the last 10 weeks of pregnancy, anticipation of delivery should be part of the medical planning. Consultation with an obstetrician must be obtained as soon as the patient enters the hospital. Besides bleeding complications, venous thrombosis with pulmonary embolism is among the most common causes of death during pregnancy. Pregnancy-related changes in physiology - increase in the resistance to flow from the lower extremities to the heart - and congenital coagulation abnormalities are most important to be recognized. This leads to the fact that superficial and deep venous thromboses occur more often in pregnancy than in the nonpregnant state. Among the coagulation abnormalities found in pregnancy are hypercoagulability (increased levels of fibrinogen, factor VII, factor VIII, factor X), decreased fibrinolytic activity due to an increased level of plasminogen activator inhibitor, increased adhesion and aggregation of platelets, decreased level of protein C and of the APC (activated protein C) ratio. Individual risks factors justifying diagnostic screening include contraception, smoking, immobilization, infection, adiposity, placental insufficiency, and a family history of thrombosis. It is even more important to establish/rule out the diagnosis of thrombosis in pregnancy than in the nonpregnant state, because the use of anticoagulants carries certain risks during pregnancy. Doppler vein studies should be used for diagnosis. If necessary, venography may be used with shielding of the maternal abdomen. Therapy consists of subcutaneous application of heparin, compression, and early mobilization. Alternatively, especially for long-term management, treatment with low molecular weight heparins is feasible. Thrombolytic treatment is contraindicated in most cases due to the high risk of bleeding complications. However, the application of thrombolytics can be contemplated in single cases after careful consideration of the pros and cons. Most cases of pulmonary embolism should also be handled conservatively with heparin. Only in massive pulmonary embolism with severe hemodynamic compromise, thrombolytic treatment is indicated. To guide future therapy in the patients, it is necessary to establish the lifetime risk of recurrent events by determining: APC resistance, prothrombin mutation 20210 A, homocysteine, AT III, protein C and S, antiphospholipid antibodies, and anticardiolipin antibodies.
 ...
PMID:[Myocardial infarction and thromboembolism during pregnancy]. 1275 75

The regulation of cerebrovascular permeability is critical for normal brain homeostasis, and the "breakdown" of the blood-brain barrier (BBB) is associated with the development of vasogenic edema and intracranial hypertension in a number of neurological disorders. In this study we demonstrate that an increase in endogenous tissue-type plasminogen activator (tPA) activity in the perivascular tissue following cerebral ischemia induces opening of the BBB via a mechanism that is independent of both plasminogen (Plg) and MMP-9. We also show that injection of tPA into the cerebrospinal fluid in the absence of ischemia results in a rapid dose-dependent increase in vascular permeability. This activity is not seen with urokinase-type Plg activator (uPA) but is induced in Plg-/- mice, confirming that the effect is Plg-independent. However, the activity is blocked by antibodies to the LDL receptor-related protein (LRP) and by the LRP antagonist, receptor-associated protein (RAP), suggesting a receptor-mediated process. Together these studies demonstrate that tPA is both necessary and sufficient to directly increase vascular permeability in the early stages of BBB opening, and suggest that this occurs through a receptor-mediated cell signaling event and not through generalized degradation of the vascular basement membrane.
 ...
PMID:Tissue-type plasminogen activator induces opening of the blood-brain barrier via the LDL receptor-related protein. 1461 49

Nonocclusive mesenteric ischemia (NOMI) is a rare abdominal pathology caused by mucosal hypoperfusion without actual obstruction to the mesenteric arteries. We present a case of NOMI after a cardiopulmonary bypass operation. The patient was a 79-year-old woman with a history of hypertension and diabetes mellitus. A coronary bypass operation was performed with stable hemodynamic conditions, and continuous venovenous hemodialysis was performed on the second postoperative day because of renal insufficiency. After 24 h of hemodialysis, the hematocrit level increased from 29.1% to 36.1%. The patient had some vague abdominal pain on the third postoperative day with abnormal laboratory values: leukocytes 17.10 x 10(3)/microl, creatine kinase 1085 U/l, glutamic-oxyloacetic transaminase 6188 U/l, and lactate dehydrogenase 8695 U/l. Selective angiography showed diffuse stenosis of the superior mesenteric artery (SMA) without any occlusive findings on the major branches; the patient was therefore diagnosed with NOMI. An infusion of urokinase and prostaglandin E1 was started; however, disseminated intravascular coagulopathy had developed and the patient died on the 21st postoperative day as a result of multiple organ failure. The autopsy demonstrated extensive necrosis and hemorrhage in the small intestine without any occlusive findings on the major branches of the SMA.
 ...
PMID:Nonocclusive mesenteric ischemia after cardiopulmonary bypass. 1555 39


<< Previous 1 2 3 4 5 6 7 8 Next >>