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)

The case of a 26 year old woman who had been taking tranexamic acid to prevent uterine bleeding due to an IUD and who died from thrombosis of the left internal carotid artery is reported. The patient's father had died at age 54 of myocardial infarction. Otherwise the family history was entirely negative for thromboembolic disease. The patient was a mild smoker. She had been previously healthy and in particular, she was not affected with hypertension, diabetes, or dyslipidemia. She had carried to term 2 uncomplicated pregnancies. 40 days prior to hospital admission her gynecologist had inserted an IUD. The insertion of the IUD was followed by persistent uterine bleeding, and for this reason she began treatment with tranexamic acid (1.5 g/daily). Uterine bleeding persisted despite this treatment, and the IUD was removed. Because of persistence of a mild uterine bleeding, tranexamic acid was continued. 2 hours before admission the patient suddenly presented a left sided hemiparesis with disarthria and vomiting. On admission she was stuporous. The left side of her face drooped and the strength of the left arm and leg was markedly decreased. Both arm and leg reflexes were symmetrical. Her blood pressure was 110/70. An electroencephalogram on arrival confirmed a right sided cerebral lesion. Subsequently the patient's condition deteriorated rapidly. She developed a full left hemiplegia and became deeply comatose. A CAT scan performed 4 hours after admission showed no abnormalities. A CAT scan performed 3 days after admission showed a large cerebral infarction involving nearly the whole right cerebral hemisphere. The patient's condition remained essentially unchanged until she died 6 days after admission. Permission for autopsy was refused. Antifibrinolytic drugs competitively inhibit plasminogen activators and noncompetitively plasmin. Thromboembolic complications after the administration of antifibrinolytic drugs have long been recognized. The use of IUDs is often associated with troublesome uterine bleeding and particularly excessive menstrual bleeding. To avoid these complaints, antifibrinolytic drugs are increasingly used.
 ...
PMID:Tranexamic acid, intrauterine contraceptive devices and fatal cerebral arterial thrombosis. Case report. 710 62

Inappropriate vascular smooth-muscle cell (VSMC) growth is the hallmark of vascular pathology in essential hypertension and diabetic macroangiopathy, whereas platelets constitute an important regulator of vessel wall homeostasis because of their content of various growth factors. Numerous abnormalities exist in platelet functions in diabetes and hypertension, such as enhanced activity and altered adhesion and aggregation. Increased thromboxane (TX2) production is characteristic of diabetes, and an elevation of intracellular free Ca2+ is found in platelets of hypertensive patients. By studying the growth patterns of VSMC from spontaneously hypertensive rats (SHRs) vs. those obtained from their normotensive counterparts, Wistar-Kyoto (WKY) rats, we have demonstrated that VSMC from SHRs exhibited a higher specific growth rate, abnormal contact inhibition, and accelerated entry into the S phase of the cell cycle. Moreover, they were hyperresponsive to many growth factors such as calf serum, epidermal growth factor (EGF), platelet-derived growth factor (PDGF), transforming growth factor beta 1 (TGF beta 1), and insulin. Additive effects were observed for EGF and PDGF or EGF and insulin. These intrinsic growth anomalies in cells of hypertensive origin persist in culture indicating their putative primary role in the pathogenesis of hypertension. Endogenous TGF beta 1 revealed an augmented expression of its message levels in SHR VSMC, the difference in mRNA between both strains being more pronounced at high cell density. Further, TGF beta 1 protein synthesis and secretion in VSMC culture were confirmed by immunoprecipitation of de novo labeled TGF beta 1. At high cell density, which most likely represents the physiological state of VSMC, plasmin, an activator of TGF beta 1, significantly stimulated DNA synthesis of VSMC in both strains. The reverse effect was obtained at low cell density. Yet, the fold stimulation was higher in WKY rats, suggesting that TGF beta 1 may be partially activated in SHR VSMC. This is supported by the inhibition of baseline DNA synthesis by TGF beta 1 neutralizing antibody in VSMC of hypertensive origin and not of normotensive controls. TGF beta 1 antisense oligodeoxynucleotide (ODN) nearly normalized the increased proliferation of SHR VSMC in culture. On the other hand, growth-promoting activity (GPA) in platelets of either diabetic or hypertensive patients was higher than in platelets of healthy controls and was found to be normalized by intensive insulin therapy in insulin-dependent diabetic patients. In hypertensive patients, however, hydrochlorothiazide (HCTZ)--even in low doses (25 mg/day)--enhanced the GPA in platelets, whereas other antihypertensive agents such as indapamide, atenolol, and captopril, had neutral effects.(ABSTRACT TRUNCATED AT 400 WORDS)
 ...
PMID:Platelets, growth factors, and vascular smooth-muscle cells in hypertension and diabetes. 750 64

Plasma total plasmin activity in spontaneously hypertensive rats (SHR) was lower than in normal Wistar rats, and in male SHR, plasmin activity was higher than that in females. However, this sex-related difference in SHR was less than that observed in our previous study in normal Wistar rats. Furthermore, we and others have reported higher levels of coagulant functions in male than in female rats. These studies were taken to indicate that there is a greater necessity for higher fibrinolytic activity in males than in females. The results of the present study suggest that hypertension is a risk factor of thrombosis in view of the increased fibrinolytic activity, and in SHR there is also a sex-related difference in plasma total plasmin activity.
 ...
PMID:Comparison of plasma total plasmin activities in male and female hypertensive rats. 767 Aug 55

Heparin-binding protein (HBP; also known as CAP37 or azurocidin) is a member of the serine proteinase family. Evolution, however, has reverted this protein into a non-proteolytic form by mutation of two of the three residues of the active-site triad. Although proteolytically inactive, the human heparin-binding protein (hHBP) is still capable of binding bovine pancreatic trypsin inhibitor (BPTI). This was demonstrated by affinity chromatography to BPTI immobilized on a solid matrix and by studies on plasmin inhibition kinetics. hHBP competes with plasmin for BPTI and this effect on plasmin inhibition has been analyzed in terms of a kinetic model. A dissociation constant, Kd = 0.1 microM, was found for the interaction between BPTI and hHBP. The hHBP provides an example of a serine proteinase which has lost its catalytic function by reverting residues of the active center while still preserving its capability of specific interactions with Kunitz inhibitors. pHBP, the porcine counterpart to hHBP, on the other hand, was incapable of BPTI binding. The structural basis for the BPTI binding to the human protein and the species difference is discussed in terms of putative three-dimensional structures of the proteins derived by comparative molecular modelling methods.
 ...
PMID:Binding of bovine pancreatic trypsin inhibitor to heparin binding protein/CAP37/azurocidin. Interaction between a Kunitz-type inhibitor and a proteolytically inactive serine proteinase homologue. 768 80

The natural history and the factors determining the expansion of aneurysms have not been elucidated. To study the respective roles of elastolysis, collagenolysis, inflammatory cells, and hypertension in the pathogenesis of aneurysms, two previously described in vivo experimental models were used. An isolated segment of the abdominal aorta was infused with 15 units of pancreatic elastase. The maximal diameter of the aorta was measured before and after infusion and the isolated aorta was excised for classic histologic and immunohistologic studies. Twelve hours after the infusion of elastase the mean diameter of the aorta increased by 30%. The aorta had a cylindric form and only collagen fibers remained. Two and a half days after the infusion the aorta was spherical in shape and the diameter increased by 300% (3.09 +/- 0.08 mm) (p < 0.05). The entire aortic wall was invested by inflammatory cells. Six days after infusion the diameter increased by 421% (4.38 +/- 0.03 mm) (p < 0.05), and immunohistochemical staining showed numerous T lymphocytes and macrophages. Between 6 and 12 days, after perfusion inflammation decreased, the final diameter was 4.23 +/- 0.14 mm (not significant). Sixteen rats had thioglycollate and plasmin infusion, which are nonspecific activators of inflammation. Nine days after infusion the diameter of the aorta had increased by 288%; the elastic fibers of the media were fragmented and rare and the entire aortic wall was invaded by inflammatory cells, predominantly macrophages. The diameter of the aorta increased progressively. Two groups of 17 hypertensive rats (renovascular and spontaneous hypertension) received an aortic infusion of 15 units of pancreatic elastase. Elastolysis overlapped the limits of the infusion and inflammation persisted after 2 weeks. The mean diameter of the aorta (F = 11, p < 0.01) and the mean length of the aneurysms (F = 11.2, p < 0.001) were significantly increased. This study demonstrates that elastolysis and especially collagenolysis are determinants of aneurysmal expansion. Inflammation may be a promoting factor in the degradation of the aortic wall. Hypertension increases the hemodynamic stress to the aorta and activates mural inflammation.
 ...
PMID:Experimental study of determinants of aneurysmal expansion of the abdominal aorta. 819 45

To clarify the effects of correction of anemia with recombinant human erythropoietin (rHuEPO) on blood coagulation, fibrinolysis and endothelium, these markers were examined in 19 regular hemodialysis patients before and 4, 8, 12 weeks on rHuEPO treatment, and 5 weeks after the end of treatment. Hematocrit significantly increased from 22.8 +/- 2.0 to 31.1 +/- 2.7% at 12 week (p < 0.001). Coagulation and fibrinolysis markers did not show significant changes except for minor and transient alteration of protein C, thrombin-antithrombin III complex and alpha 2-plasmin inhibitor plasmin complex (PIC) throughout the treatment. Endothelin and 6-keto-prostaglandin F1 alpha (PGF1 alpha) significantly increased from 6.1 +/- 4.5 to 14.2 +/- 2.9 pg/ml (p < 0.001) and from 51.9 +/- 14.7 to 66.5 +/- 18.5 pg/ml (p < 0.05) at 12 week, respectively. Human atrial natriuretic peptide (ANP) significantly decreased from 277.9 +/- 88.6 to 179.4 +/- 73.3 pg/ml at 12 week (p < 0.001). Endothelin and PGF1 alpha after 6 month treatment with rHuEPO showed high values as same as those of 12 weeks. These data suggests that rHuEPO therapy did not affect blood coagulation and fibrinolysis, however exerts effects on the endothelium. Changes in endothelial function after rHuEPO may be one of the pathogenetic mechanisms of hypertension and may contribute to a decrease in thrombotic complications.
 ...
PMID:[Changes in endothelial vasoactive substances and blood coagulation and fibrinolysis functions under recombinant human erythropoietin therapy in hemodialysis patients]. 831 81

Catastrophic stress induced by Hanshin-Awaji earthquake seems to promote rheological deterioration associated with high blood pressure, increased blood viscosity due to hemoconcentration and increased fibrinogen level. These changes lead to prolonged endothelial cell dysfunction demonstrating high levels of von Willebrand factor, tissue type plasminogen activator and plasmin.alpha 2 plasmin inhibitor complex, and accelerate fibrin turnover as the result of a high D-dimer level from the post earthquake period until 4-6 months later. There were remarkable changes in biochemical parameters except for uric acid, BUN, triglyceride level. An increase in these acute changes caused by mental and physical stress might trigger obstructive thrombus in coronary arteries in the elderly after an earthquake. In conclusion, earthquake induced stress could be considered a transient cardiovascular risk factor.
 ...
PMID:[Role of biochemical and fibrinolytic parameters on cardiac events associated with Hanshin-Awaji earthquake-induced stress]. 969 69

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

L-Arginine (Arg) is the substrate for the synthesis of nitric oxide (NO), the endothelium-derived relaxing factor essential for regulating vascular tone and hemodynamics. NO stimulates angiogenesis, but inhibits endothelin-1 release, leukocyte adhesion, platelet aggregation, superoxide generation, the expression of vascular cell adhesion molecules and monocyte chemotactic peptides, and smooth muscle cell proliferation. Arg exerts its vascular actions also through NO-independent effects, including membrane depolarization, syntheses of creatine, proline and polyamines, secretion of insulin, growth hormone, glucagon and prolactin, plasmin generation and fibrinogenolysis, superoxide scavenging and inhibition of leukocyte adhesion to nonendothelial matrix. Compelling evidence shows that enteral or parenteral administration of Arg reverses endothelial dysfunction associated with major cardiovascular risk factors (hypercholesterolemia, smoking, hypertension, diabetes, obesity/insulin resistance and aging) and ameliorates many common cardiovascular disorders (coronary and peripheral arterial disease, ischemia/reperfusion injury, and heart failure). Dietary Arg supplementation may represent a potentially novel nutritional strategy for preventing and treating cardiovascular disease.
 ...
PMID:Arginine nutrition and cardiovascular function. 1105 97


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