Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: EC:3.4.21.4 (trypsin)
 42,187 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The molecular weight (MW) of active renin (AR) and inactive renin (IR) was investigated in individual plasma samples from 15 essential hypertensive and 5 normal subjects. The patients with essential hypertension were classified into 3 subgroups: low plasma renin activity (PRA), normal PRA and high PRA. The MW of AR and IR was estimated by Sephadex G-100 gel filtration. IR in the eluates was activated with trypsin. Plasma renin activity and renin activity in eluates were measured by radioimmunoassay of angiotensin I. At least 3 sizes of AR (MW: 48,000, 53,000 and 57,000) and 2 sizes of IR (MW: 53,000 and 57,000) were discovered, and the MW of AR was less than or equal to the MW of IR. The larger AR was predominant in the low PRA group and the smaller one in the high PRA group. This was also true for IR. This relation was also observed in the 2 types (high renin and low renin) of pooled plasma. In high renin pooled plasma the MW of AR and IR was about 48,000 and 54,000, respectively, while both were about 56,000 in low renin pooled plasma. It appears that the larger type of AR and IR remains in the circulation in the suppressed renin state, and that the smaller type of renins enters into the circulation when the secretion of renins is enhanced.
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PMID:Studies on the molecular weight of active and inactive renins in essential hypertension. 633 70

We developed new sensitive direct radioimmunoassay for human plasma renin. Renin was purified from Haas' preparation utilizing a pepstatin-C6-Sepharose affinity chromatography. Antiserum, prepared by immunizing rabbits with the purified renin, was used for the direct radioimmunoassay at a final dilution of 1:30,000. The antibody was specific for human renal and plasma renin, but did not cross-react with cathepsin D, trypsin, or renins of mouse, dog, and rat. Radioimmunoassay was performed by the double antibody technique using the delayed tracer addition method. In this method, a standard curve was obtained over a range from 0.2 to 8.0 ng/ml. The values from our assay correlated well with total renin activity measured as the generation rate of angiotensin I after trypsin activation (r = 0.78, p less than 0.01), but correlated weakly with active renin activity. This finding disclosed that both active and inactive renin were detected by this method. In normal participants, plasma renin concentration determined by direct radioimmunoassay was increased by standing and furosemide injection. The plasma renin concentration determined by direct radioimmunoassay of patients with essential hypertension (0.7 to 1.7 ng/ml) was not significantly different from values in normal controls (0.8 to 1.9 ng/ml). The values were higher in patients with renovascular hypertension (1.6 to 2.7 ng/ml), malignant hypertension (2.8 to 3.4 ng/ml) and Bartter's syndrome (1.8 to 2.5 ng/ml), but lower in patients with primary aldosteronism (0.4 to 0.8 ng/ml) than in normal controls. This newly developed radioimmunoassay for human renin was sensitive enough to estimate the levels of renin in plasma of patients with low renin hypertension. It provides a new tool for the understanding of the renin-angiotensin system under various clinical conditions.
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PMID:A new sensitive direct radioimmunoassay for human plasma renin and its clinical application. 638 35

A sensitive direct human renin radio-immunoassay has been developed for clinical use. The antigen source was human renal renin purified from Haas' preparation by pepstatin-C6-sepharose affinity chromatography, this was used to prepare a specific human renin antibody. The radio-immunoassay was performed by the double antibody technique using the delayed tracer addition method. Standard curves were obtained over the range 0.2-8.0 ng/ml. Dilution curves of human renal renin and human plasma were superimposable on the standard curve. Both active and inactive renin were detected by this method, and measurements correlated well with total renin activity after trypsin activation. Intra- and inter-assay coefficients of variance were 4.6% and 5.1%, respectively. Renin concentration was higher in patients with renovascular hypertension (1.97 +/- 0.38 ng/ml, mean +/- s.d., n = 10, P less than 0.01), but lower in primary aldosteronism (0.66 +/- 0.16 ng/ml, n = 13, P less than 0.01) compared with essential hypertension (1.38 +/- 0.34 ng/ml, n = 12). This method provides a new tool for the investigation of the renin-angiotensin system in man.
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PMID:Sensitive direct radio-immunoassay for human renin. 640 Mar 70

The effect of age on the levels of active and trypsin-activatable inactive plasma renin was examined in 41 normal subjects and 54 patients with essential hypertension, during recumbency and after stimulation with furosemide and ambulation. Active renin levels in supine subjects and patients decreased with age. Inactive renin levels did not change with age in normal subjects, whereas in hypertensive patients they decreased with age. Following stimulation with furosemide and ambulation, the levels of active renin increased but the responsiveness to stimulus decreased with age in both groups. In contrast, inactive renin levels slightly increased after furosemide administration and ambulation, resulting in increased proportion of active to total renin. These data show that an acute stimulation with furosemide and ambulation affects mainly the active form of plasma renin, and the effect of age on inactive plasma renin in normal subjects may be different from that in patients with essential hypertension.
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PMID:Effect of age on active and inactive plasma renin in normal subjects and in patients with essential hypertension. 702 46

Plasma levels of kininogen, kallikrein, and prekallikrein were determined in patients with malignant hypertension (MH) and compared to normotensive controls (NC) and patients with mild to moderate essential hypertension (EH). Also, a recently described kinin potentiating factor (KPF) was estimated by dividing the value of kininogen determined by trypsin (Kgn-Try) by that of kininogen determined by human urinary kallikrein (Kgn-HuUk). No significant alterations were detected among plasma values of pre-kallikrein and kallikrein of MH as compared to NC. However, Kgn-HuUK values were significantly lower in MH (1.9 +/- 0.3 micron gLBK/ml) as compared to EH and NC (2.7 +/- 0.1 micron gLBK/ml and 3.0 +/- 0.2 micron gLBK/ml respectively, p less than 0.05). Furthermore, KPF values were also low (p less than 0.05) in MH (1.6 +/- 0.3) when compared with similar values obtained in EH and NC (3.0 +/- 0.2 and 2.8 +/- 0.1, respectively). Adequate control of blood pressure levels for 90 days in MH group caused no significant alterations in plasma levels of kininogen and KPF. It is suggested that diminished kininogen levels as well as a decrease in a kinin potentiation KPF that is generated in plasma by trypsin may be involved in the pathogenesis of human malignant hypertension.
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PMID:Malignant hypertension: a syndrome associated with low plasma kininogen and kinin potentiating factor. 702 21

In 25 hypertensive patients (15 with renal artery stenosis and 10 with essential hypertension), captopril, in a single 12.5 mg dose, caused a prompt decrease in arterial pressure without changing the heart rate. Plasma active and trypsin-activated renin significantly increases, whereas inactive renin and plasma aldosterone decreased. The plasma active/inactive renin ratio was also increased, suggesting that captopril, together with a release of active renin, may induce an in vivo activation of inactive renin. No correlations were found between blood pressure changes and both pretreatment and captopril-induced variations of active, inactive and trypsin-activated renin or the active/inactive ratio. However, the percent decrease in mean arterial pressure was significantly related to the increase in the active/inactive renin ratio in a group of patients whose blood pressure was brought to normal (r = -0.78; p less than 0.001). This finding suggests the possibility that vasodilating substances, in addition to inhibiting angiotensin II formation, might play some role both in exerting a full effect of captopril on blood pressure and in triggering the in vivo mechanisms of inactive renin activation.
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PMID:Active and inactive renin after a single dose of captopril in hypertensive patients. 704 96

The role of the kidney as a possible source or as activator of inactive renin was studied in 22 patients with Essential Hypertension (EH) and in 20 patients with Unilateral Renal Artery Stenosis (RAS). Active and inactive renin (trypsin activation) were measured in blood samples taken simultaneously from both renal veins and from a peripheral artery during acute diuretic stimulation induced by furosemide 40 mg i.v. In EH pts active and trypsin-activated renin were significantly higher in both renal veins than in arterial blood (P less than 0.001 and P less than 0.02 respectively) whereas no difference was seen as far as inactive renin is concerned. In unilateral RAS trypsin-activated and active renin from the ischemic kidney were significantly higher (P less than 0.01 and P less than 0.005 respectively) while inactive renin was significantly lower (P less than 0.005) than in arterial blood. No significant difference was seen between arterial and renal venous blood from the contralateral kidney as far as active and inactive renin are concerned. When comparing the V-A differences for active renin to the corresponding V-A differences for inactive renin from the ischemic kidney a significant negative correlation appeared (r = -0.49 p less than 0.05) whereas no correlation was found from the contralateral kidney (r = -0.26 n.s.). These data demonstrate that the ischemic kidney, in addition to its ability to release active renin, can also activate circulating inactive renin.
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PMID:In-vivo activation of circulating inactive renin by the ischemic kidney in man. 704 6

Parabiosis and cross-circulation experiments with spontaneously hypertensive and normotensive rats gave indications for a previously unidentified circulating hypertensive agent. In this study, plasma from normotensive and hypertensive rats was fractionated and the vasopressor action of the corresponding fractions was measured in the isolated perfused rat kidney. One of three vasoactive fractions obtained by gel filtration (Biol-Gel P2) from hypertensive rats showed a significantly higher activity (increase in perfusion pressure by 1502.9 +/- 438.9 Pa) than that from normotensive rats (increase in perfusion pressure by 505.4 +/- 186.2 Pa, P < 0.01). Further chromatographic separations of this fraction revealed that the hypertensive factor is hydrophilic and has no ionic groups or vicinal diol groups. The molecular mass was estimated by dialysis and the matrix-assisted laser desorption/ionization mass spectrometry to be in the range of 1 kDa. The vasopressor is heat resistant and not degradable with trypsin or carboxypeptidase Y. The vasopressor action was not inhibited with the angiotensin-II-receptor antagonist saralasin, the alpha-receptor antagonist phentolamine, the thromboxane-receptor antagonist carbocyclic thromboxane A2 or the serotonin antagonist ketanserin. The results confirm the existence of a vasopressor factor in the plasma of hypertensive rats and, in a lower concentration, of normotensive rats, which is possibly related to the pathogenesis of essential hypertension. The chromatographic behavior suggests that this factor is different from the parathyroid hypertensive factor described recently.
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PMID:Partial purification and characterization of a circulating hypertensive factor in spontaneously hypertensive rats. 824 78

Mast cells have recently been related to nonallergic chronic organ damage and fibrosis. In the present study, we analyzed mast cell number, localization, and maturation in the kidney of a relatively unique group of middle-aged accident victims with primary essential hypertension and in normotensive controls (n=8 per group, Caucasians, predominantly male). Hypertensive kidneys showed a significantly higher degree of arteriolosclerosis. However, glomerular and tubulointerstitial matrix accumulation did not differ significantly to normotensive controls indicating a relatively early stage of hypertensive nephropathy. Using toluidine blue staining, renal mast cell number was found to be fivefold higher in hypertensive subjects compared with normotensive controls. Mast cells were primarily located in the peritubular interstitial spaces, some perivascular, but not in glomeruli. In a series of immunohistological staining studies, mast cell maturation grading showed that expression of early hematopoietic precursor cell marker CD34 did not differ between both groups. In contrast, mast cells were mostly positive for IgE receptor, tryptase, and chymase indicating a mature, differentiated cell phenotype in hypertensive nephropathy. Renal expression of stem cell factor was markedly upregulated in primary hypertension. Kidney macrophage and lymphocyte numbers were similar in both groups. In conclusion, human hypertensive kidney disease shows an early and conspicuous upregulation of stem cell factor along with an increased number of mature mast cells. The results suggest that renal mast cell accumulation may play a role in the pathogenesis of human hypertensive nephropathy.
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PMID:Increased mast cell number in human hypertensive nephropathy. 1868 89

Essential hypertension is a disease of unknown pathogenesis, although renal function has been implicated as an important factor in its cause. Stroke-prone spontaneously hypertensive (SHRSP) rats provide an animal model of essential hypertension. To understand the cause of hypertension, identifying proteins that are differentially expressed between hypertensive and normotensive rats may provide a key. Here, proteins in the renal cortex from SHRSP rats, malignant stroke-prone spontaneously hypertensive (M-SHRSP) rats, and Wistar Kyoto (WKY) rats as a normotensive control were subjected to two-dimensional difference gel electrophoresis (2D-DIGE). After in-gel digestion by trypsin, proteins were identified by matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOFMS). Several proteins showed differential expression patterns between hypertensive and normotensive rats. Among them, we focused on catechol-O-methyltransferase (COMT) because this enzyme inactivates catecholamines, possibly affecting blood pressure. To confirm the differential expression of COMT in each animal, we conducted Western blot analysis, which revealed that the expression of COMT is lower in M-SHRSP rats than in control and SHRSP rats, indicating that blood pressure and expression of COMT are related. In fact, the blood pressure of M-SHRSP rats was significantly higher than that of SHRSP rats at age of 10 weeks. Immunohistochemical and immunofluorescence studies showed that COMT in renal cortex is localized in tubular epithelial cells. The expression of COMT is lower in the renal cortex tubular epithelium of M-SHRSP rats than in normotensive rats. These results suggest that the decreased expression of COMT may be an important factor leading to the development of hypertension.
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PMID:Decreased expression of catechol-O-methyltransferase in the renal cortex of malignant spontaneously hypertensive rats. 1996 33


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