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)

Urinary kallikrein and kallikrein activity significantly decreased in cases of preeclampsia (u-kall./CRE.index 42.39 +/- 9.66 ng/mg, u-kall. act./CRE.index 0.26 +/- 0.06 ng/min/mg), and urinary kininase II and kininase activity significantly increased (u-kininase/CRE.index 10.91 +/- 1.26 x 10(-3) IU/min/mg, u-kininase act./CRE.index 506.37 +/- 178.45 pg/min/mg) when compared with those of normal gravidas from 28 weeks to 42 weeks of gestation (u-kall./CRE.index 189.31 +/- 14.17 ng/mg, u-kall. act./CRE index 1.08 +/- 0.10 ng/min/mg, u-kininase/CRE.index 6.24 +/- 0.31 x 10(-3) IU/min/mg, u-kininase act./CRE.index 15.64 +/- 0.10 pg/min/mg). Urinary FPA, B beta 5-42, alpha 2-PI, and alpha 2PI-plasmin-complex (PIC) significantly increased in preeclampsia (u-FPA/CRE.index 23.59 +/- 8.47 ng/mg, u-B beta/CRE.index 105.26 +/- 29.30 ng/mg, u-alpha 2PI/CRE.index 121.53 +/- 43.57 ng/mg, u-PIC/CRE index 278.39 +/- 60.50 ng/mg) when compared with those of normal control group (u-FPA/CRE.index 0.92 +/- 0.04 ng/mg, u-B beta/CRE.index 12.15 +/- 0.44 ng/mg, u-alpha 2PI/CRE.index 4.18 +/- 0.33 ng/mg, u-PIC/CRE.index 5.98 +/- 1.15 ng/mg). Urinary urokinase markedly increased and urinary D-dimer was detected in severe cases of preeclampsia (u-UK/CRE.index 58.20 +/- 43.69 ng/mg, u-D-dimer 54.76 +/- 9.89 ng/ml) when compared with those of normal control group. These findings suggest that deficiency in urinary kinin excretion may induce hypertension in addition to the changes of urinary coagulation-fibrinolysis system that represents the occurrence of either the endothelial cell injury in the glomerulus or the renal tulbular damage in mild cases of preeclampsia, eventually resulting in the intra-renal vascular coagulation.
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PMID:Urinary coagulation-fibrinolysis, kallirein-kinin systems and kininase in cases of preclampsia. 133 34

Parameters of fibrinolysis, including euglobulin fibrinolytic activity, tissue-type plasminogen activator (t-PA) antigen, plasminogen activator inhibitor (PA-inhibitor) activity, and plasmin-alpha 2-antiplasmin complex (PAP) were studied in 62 patients (35 women and 27 men; ages 53 +/- 16 years) with either insulin-dependent (IDDM) or noninsulin-dependent (NIDDM) diabetes mellitus. Compared to a control group of similar age (n = 57), the diabetic patients had a significantly lower mean euglobulin fibrinolytic activity (1.2 +/- 0.7 vs. 1.7 +/- 1.1 ng/ml, p less than 0.01) but significantly higher mean t-PA antigen (15.7 +/- 8.4 vs. 6.6 +/- 2.9 ng/ml, p less than 0.001) and PA-inhibitor activity (2.6 +/- 1.3 vs. 1.5 +/- 0.7 IU/ml, p less than 0.001) levels. Significant univariate correlations were observed between PA-inhibitor activity and age (r = 0.32, p less than 0.05), diastolic blood pressure (r = 0.42, p less than 0.01) and euglobulin fibrinolytic activity (r = -0.40, p less than 0.01). In multivariate analysis, only body mass index (positively) and euglobulin fibrinolytic activity (negatively) remained significantly related to PA-inhibitor activity in the total diabetic population as well as in the NIDDM group. The only parameter in the IDDM group significantly related to PA-inhibitor activity was diastolic blood pressure. These results suggest that PA-inhibitor plays a role in the regulation of fibrinolysis in diabetes patients and that factors like obesity and hypertension may be related to reduced fibrinolysis via PA-inhibitor levels.
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PMID:Tissue-type plasminogen activator antigen and plasminogen activator inhibitor in diabetes mellitus. 244 56

Chronic hypertension was induced in rats after partial nephrectomy. The systolic blood pressure was significantly elevated from the first week after nephrectomy to the end of the experimentation (8th week). Plasminogen activator activity (PAA) and plasminogen activator inhibition (PAI) showed a tissue- and time-dependent pattern of changes in some key organs compared to controls (sham-operated rats). Two weeks after nephrectomy (one week after the induction of hypertension) the PAA was markedly increased in lungs, heart and aorta. In aorta the PAA continued to be enhanced until the end of the experimentation (the 8th week after nephrectomy), while in heart and lungs the PAA returned to the normal eight weeks after nephrectomy. In vena cava, brain and liver no change in PAA was noticed compared to controls. Tissue PAI was mostly increased or unchanged, while tissue plasmin inhibition (PI) was unchanged. The differential response of PAA and PAI was varying not only from one organ to another or in the same organ at a given time but also in the same organ throughout experimentation. In a number of nephrectomized rats, however, hypertension was not induced. In these rats similar changes in tissue PAA and PAI were noted compared to hypertensive nephrectomized rats. Therefore, all the changes in the parameters studied should be due to the partial nephrectomy itself. In conclusion, experimentally induced chronic hypertension had not any effect on tissue PAA, PAI and PI.
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PMID:The effect of experimental chronic hypertension on tissue plasminogen activator activity, plasminogen activator inhibition and plasmin inhibition. 253 94

A series of acetyl-peptidyl-amides containing the amino acid sequence around the Arg-Ser kallikrein cleavage site of bovine kininogen were synthesized and tested for their ability to inhibit both the kinin-releasing activity and the amidase activity of purified human urinary kallikrein. The substrate analogues were competitive inhibitors for human urinary kallikrein and the heptapeptides (P4-P3'), hexapeptides (P3-P3'), and pentapeptides (P2-P3') gave Ki values of 140, 64, and 18 microM respectively, while the tetrapeptides (P1-P3'), tripeptides (P1'-P3') and dipeptides (P2'-P3') had little or no inhibitory activity. The effective analogues had neither kinin-like nor kinin-blocking activity on the rat uterus either before or after exposure to human urinary kallikrein. The effective human urinary kallikrein inhibitors were further examined for their effect on other serine proteases, including human plasma kallikrein, plasmin, complement components (C1s, C1r), bovine coagulation factors (IIa, IXa, and Xa), elastase, and trypsin. These peptides showed little inhibition of the circulating serine proteases but yielded a Ki for the nonspecific protease trypsin in the microM range. These results should provide the basis for the development of highly specific tissue kallikrein inhibitors to aid in elucidating the in vivo role(s) of tissue kallikreins.
Hypertension
PMID:Specificity of substrate analogue inhibitors of human urinary kallikrein. 384 67

A highly active angiotensin-producing enzyme (enzyme II) was obtained from dog serum by acid treatment and fractionation to remove angiotensinase and converting enzyme, separate an inhibitor, and convert an inactive precursor (proenzyme II) to enzyme II. Proenzyme II was found to be converted to enzyme II by an endogenous activating enzyme identified as plasmin. Conversion was also caused by the interaction of bacterial streptokinase with human proactivator, by trypsin, and by an activator formed from liver tissue extract and dog serum. Neither plasma kallikrein nor the labile, human extrinsic tissue-type plasminogen activator induced activation. The inhibitor, which normally blocks the activation of proenzyme II, was unusually stable against high temperatures and extremes of pH, and it was not identical to any of the six known protease inhibitors of serum. Enzyme II was not identical to other angiotensin-producing enzymes such as enzyme I, renin, cathepsin D, pepsin, plasmin, tonin, or cathepsin G. Enzyme II reacted maximally at pH 4.7 and produced up to 2250 ng of angiotensin I/ml serum/hr from the substrate of dog serum (i.e., amounts 3200-fold higher than that produced by endogenous renin of normal dog serum). Since at pH 7.2, angiotensin I formation is still about 30 times higher than that of renin, enzyme II may be physiologically active under some conditions.
Hypertension
PMID:Angiotensin-producing serum enzyme II. Formation by inhibitor removal and proenzyme activation. 390 15

A highly-standardized plate method was used to study fibrinolytic profiles in 14 patients with essential hypertension and 245 normotensive healthy control subjects. Compared with the normotensive group, the group with essential hypertension showed a defect in fibrinolysis, as evidenced by a significant increase in the mean level of inhibitor of plasminogen activation, and a subset of the hypertensive patients also showed a significant decrease in the mean level of vascular plasminogen activator. There were no significant differences between the two groups in relation to plasma fibrinogen level, total fibrinolytic activity and plasmin inhibitor. The alterations in inhibitor of plasminogen activation and vascular plasminogen activator in the patients with essential hypertension may reflect a defect in the fibrin-clearing mechanism and, perhaps, contribute to the vascular complications of hypertension.
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PMID:Abnormalities of fibrinolysis in essential hypertension. 624 55

An assay of plasma prorenin was developed in which the conversion to renin occurred under apparently optimal conditions. Some characteristics of the assay were 1) prorenin was activated by Sepharose-bound trypsin at 4 degrees C; 2) the concentration of activator was not critical provided that incubation was prolonged until renin activity had reached a plateau; and 3) this plateau was stable and had the same height as after maximal activation with acid, pepsin, plasmin or urokinase. Maximal activity with Sepharose-bound trypsin at 4 degrees C was higher than with cryoactivation, and optimal conditions were more readily reproduced than with trypsin at 37 degrees C or with acid-activation. The assay was used for measurements in peripheral and renal vein plasma after captopril in hypertensive patients with unilateral renal artery stenosis. Peripheral renin rose within 30 minutes after a first dose of captopril, 50 mg orally, and it remained high with chronic treatment. In contrast, peripheral prorenin fell initially and rose after 4 hours. These changes in peripheral plasma were related to changes in the secretion rates of the two forms of renin from the affected kidney. Thus chronic, but not acute, stimulation of renin release was associated with an increased secretion rate of prorenin. The late rise in prorenin is probably an indication of enhanced synthesis in the kidney, so that more prorenin is available for conversion. The data suggest that prorenin is indeed a biosynthetic precursor of renin and that, at least under certain circumstances, a major proportion of circulating prorenin originates from the kidney.
Hypertension
PMID:Asynchronous changes in prorenin and renin secretion after captopril in patients with renal artery stenosis. 633 53

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

Kallikrein is present in the renal tubule near the macula densa, and it has recently been shown to activate inactive renin in human plasma. We recently showed that kallikrein was a potent stimulus of renin release and increased renin secretion in a dose-dependent fashion. To study its effect on renal renin release, we superfused rat renal cortical slices with purified rat urinary kallikrein. Kallikrein-stimulated renin release was completely abolished by trasylol and by amiloride, but was not affected by soybean trypsin inhibitor. Indomethacin did not block kallikrein action, indicating that kallikrein's effect is not mediated via kinin generation and prostaglandins. Kallikrein-stimulated renin release was not blocked by propranolol, trasylol did not block isoproterenol, and dibutyryl cyclic AMP stimulated renin release, indicating that kallikrein may not play a role in the beta-adrenergic mechanism of renin release. There was no demonstrable acid-activatable or kallikrein activatable renin in the superfusate, suggesting that all of the renin release was in the active form. Cathepsin D and plasmin also stimulated renin release from kidney slices in pH 6.0 buffer, whereas trypsin and pepsin did not. Our results support the hypothesis that kallikrein may play a role in the secretion of renin by the kidney. Other proteases can also release renin from the kidney.
Hypertension
PMID:Direct action of kallikrein and other proteases on the renin-angiotensin system. 702 11

Inactive renin and active renin from human kidney and human plasma were prepared in highly purified forms by three steps of chromatography on Octyl-Sepharose, immunoaffinity chromatography, and pepstatin-amino hexyl Sepharose CL-4B. The inactive renin and active renin from human kidney had molecular weights of 51,000 and 44,000 as measured by a calibrated gel filtration column run with internal molecular weight standards. Molecular weights of plasma inactive renin and active renin were 56,000 and 51,000 respectively. Both inactive and active renins were found to be heterogeneous, consisting of several components with different isoelectric points. Renal inactive renin has higher pI values of 6.40, 6.10, 5.90, 5.61, and 5.40. Renal active renin has pI values of 5.73, 5.40, 5.25, and 5.13. The pI values of plasma inactive renin were 6.37, 6.08, 5.77, 5.36, and 5.25; of plasma active renin, 5.68, 5.40, 5.33, and 5.25. Trypsin activation and plasmin activation of plasma inactive renin produced an active enzyme with similar molecular weight but lower pI values. Acid activation of inactive renin did not change the molecular weight and pI values.
Hypertension
PMID:Isolation and activation of inactive renin from human kidney and plasma. Plasma and renal inactive renins have different molecular weights. 702 7


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