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)

Estimation of apparent molecular weight (mw) of inactive renin by gel filtration of human plasma was found to be inaccurate when "acid activation" or "cryoactivation" was used for detection; recoveries were only 5% to 20%. Trypsin activation produced greater recoveries, but the apparent elution volume of inactive renin varied with the concentration of trypsin used; the presence of trypsin inhibitors increased trypsin requirements to 100 to 200 micrograms/ml in the 60,000 dalton region, while low protein concentration in the 50,000 dalton region resulted in destruction of renin by as little as 10 microgram/ml trypsin. A composite trypsin-activated inactive renin peak corresponded to a mw of 56,000 +/- 1500 daltons (104% to 120% recovery), while active plasma renin was 48,000 +/- 2000 daltons. When this prorenin-like substance was isolated by affinity chromatography, it was found to be completely inactive. It was also nearly free of trypsin inhibitors, so that a single trypsin concentration correctly identified and confirmed the elution characteristics of inactive renin peak following gel filtration. The apparent mw of trypsin-activated inactive renin was slightly lower (52,000 daltons) than that of inactive renin. Human renal cortex was also found to contain a trypsin-activable form of renin. Like plasma inactive renin, it could be isolated by chromatography on Cibacron blue-agarose (Affi-Gel blue). It was found to be completely inactive following passage over a pepstatin affinity column. This inactive renal renin, as well as a similar substance in perfusate of normal human kidney, had a mw of 49,500 +/- 1000, while active renal renin was 39,500 +/- 500. Trypsin-activated inactive renal renin had a mw of 46,500 +/- 500; its pH optimum was identical with that of active renal renin, and it no longer bound to Cibacron blue-agarose. We conclude that both human plasma and kidney contain an inactive, prorenin-like substance that can be detected reliably by trypsin activation. There appear to be slight differences in the apparent mw of plasma renins and kidney renin, but the similarity of other characteristics suggests that the inactive, prorenin-like substances in renal cortex, renal perfusate, and plasma may be one and the same substance.
Hypertension
PMID:Detection and isolation of inactive, large molecular weight renin in human kidney and plasma. 702 14

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.
Hypertension
PMID:Malignant hypertension: a syndrome associated with low plasma kininogen and kinin potentiating factor. 702 21

We isolated renin granules from cadaver kidneys using discontinuous sucrose density gradient centrifugation, and investigated the storage form of the renin from these granules. Approximately 23% of the total renin activity in the original homogenate was obtained from the surface phase between 1.6 and 1.7 M sucrose (Fraction 6). Granule renin extracted from the granules in Fraction 6 was separated into active and inactive renin using pepstatin affinity chromatography. Only the active renin had an affinity for pepstatin. The inactive renin, albeit activated by trypsin, was little activated by acidification. The proportion of inactive renin was about 25% of the total granule renin (active renin + inactive renin). Trypsin concentrations over 10 micrograms/ml resulted in a decrease in the renin activity of the trypsin-activated renin, but the enzymatic activity of active renin was decreased by trypsin. With gel filtration, the inactive renin revealed a single peak, and the molecular weight (MW) was 48,000. The active renin had a MW of 44,000. The inactive renin could be activated by trypsin without an apparent change in molecular weight.
Hypertension
PMID:The storage form of human renal renin. 704 Feb 25

Inactive renin was partially purified from 4.5 liters of human plasma (502-fold, specific activity 0.8 X 10(-3) Goldblatt units/mg protein) and from 207 g renal cortex (103-fold, 52 X 10(-3) Goldblatt units/mg). In contrast to active renin, inactive renin from each source bound to Cibacron blue-agarose and was unable to bind to pepstatin-Sepharose. Both plasma and renal inactive renin had weaker affinity for anion-exchange resins than the active form, both bound to concanavalin A-Sepharose and were eluted with carbohydrate, and both bound tightly to hydrophobic gels. Each substance could be isolated in a completely inactive form during small-scale pilot studies, but "spontaneous" activation did occur, to a limited degree, during large-scale purification; this was possibly due to a plasma serine protease that fractionated with inactive renin during the initial purification steps. Both plasma and renal inactive renin were activated irreversibly by trypsin. Following activation, each substance lost it ability to bind to Cibacron blue-agarose. Each could be activated fully by acidification at 4 degrees C, but this activation was reversed during subsequent incubation at higher temperature and pH. There was no evidence of acid protease activity in either preparation. Activated inactive renin from both plasma and kidney were identical to partially-purified active renal renin in terms of pH optimum (pH 5.5-6.0) and reaction kinetics (Km 0.8-1.3 microM) with homologous angiotensinogen, noncompetitive inhibition by pepstatin (ki 2.5-3.5 microM), and an identical inhibition profile by monospecific antirenin antibodies. These results suggest that inactive renin from plasma and kidney may be the same substance and that their activated forms are similar to the endogenously produced active enzyme, consistent with the possibility that inactive renin is a precursor of circulating active renin.
Hypertension
PMID:Biochemical similarity of partially purified inactive renins from human plasma and kidney. 704 Feb 42

The levels of active, inactive, and total renin (trypsin treatment) were measured in rat plasma before and after in vivo stimulation or suppression of active plasma renin. Stimulation of active renin was accompanied by either an increase (low sodium diet), no change (pentobarbital anesthesia plus hemorrhage), or fall (pentobarbital anesthesia) in the plasma levels of inactive renin, while suppression of active renin was accompanied by a fall (high sodium diet) or mild but nonsignificant increases (clonidine or saline infusion) of the inactive enzyme. These results suggest the possible independence of in vivo regulation of active and inactive renin in the rat. Trypsin activation of plasma fractions obtained by isoeletric focusing indicated a minimum of three activable forms of inactive renin (pH 4.4, 4.6, 4.8). Inactive enzymes could not be completely separated from active renins by this technique. Isoelectric focusing indicated a similar lowering of the isoelectric points of the five detectable active renins of rat plasma following in vivo stimulation of the renin system (ether anesthesia plus hemorrhage) or trypsin treatment of normal rat plasma before fractionation. These results indicate that similar renins are activated both in vivo and in vitro. Although trypsin is not the physiological activator of renin, a similar enzymatic cleavage resulting in activation appears to occur in vivo.
Hypertension
PMID:In vivo and in vitro alterations of active and inactive plasma renins in the rat. 704 Feb 41

We used the anesthetized sheep lung lymph preparation to examine the effects of acute hemorrhagic pancreatitis on pulmonary transvascular fluid and protein exchange. Induction of acute pancreatitis by injection of trypsin and sodium taurocholate into the pancreatic duct caused significant increases (p less than 0.05) in lung lymph flow, ratio of lymph to plasma protein concentration (L/P ratio), and transvascular protein clearance. Pulmonary arterial and pulmonary arterial wedge pressures did not change significantly, but pulmonary blood flow decreased (p less than 0.05) and pulmonary vascular resistance increased (p less than 0.05). In contrast to the effects of acute pancreatitis, left atrial hypertension caused increases in lung lymph flow that were associated with decreases in the L/P ratio. Extravascular lung water content was increased after acute pancreatitis by 25% from the value obtained in sham-operated animals in which saline was injected into the pancreatic duct. These findings indicate that acute hemorrhagic pancreatitis causes an increase in pulmonary vascular permeability to proteins. Because pulmonary vascular pressures did not change, the increased permeability may be due to the cellular and humoral factors rather than hemodynamic mechanisms.
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PMID:Effect of acute pancreatitis on pulmonary transvascular fluid and protein exchange. 727 Oct 55

Many properties of urinary kallikrein are well characterized, but the intracellular processing of prokallikrein and release by kidney cells have yet to be clarified. We report here on the synthesis of prokallikrein in Madin-Darby canine kidney (MDCK) cells transfected with rat submaxillary gland kallikrein cDNA and on its activation by MDCK cells and by an enriched liver Golgi membrane preparation. Transfected MDCK cells secreted only prokallikrein at both the apical and basolateral sides in about a 4:1 ratio, but cells transfected with kallikrein cDNA in reverse orientation or untreated cells released only traces of the enzyme. Prokallikrein, in culture medium or in homogenized MDCK cells, was fully activated by trypsin but activated only to 44% by thermolysin. Prokallikrein was synthesized and released into the medium at a high rate: the enzyme secreted by 5 x 10(6) cells in 24 hours cleaved 46 nmol/min D-Val-Leu-Arg-7-amino-4-methylcoumarin and liberated 63 ng/min bradykinin after activation. Immunocytology indicated the association of prokallikrein with the Golgi apparatus in the transfected cells. Antiserum to rat urinary kallikrein detected a single band in a Western blot of conditioned medium and also immunoprecipitated the enzyme. Aprotinin inhibited activated prokallikrein. Although MDCK cells released prokallikrein, their homogenates activated prokallikrein at both pH 5.5 and 7.5. Prokallikrein was also activated by a highly enriched liver Golgi membrane fraction and by an endoplasmic reticulum preparation, but the Golgi preparation was 38-fold more active. The activation was blocked significantly by inhibitors of serine proteases and less by cysteine protease inhibitors.(ABSTRACT TRUNCATED AT 250 WORDS)
Hypertension 1995 Dec
PMID:Expression of rat kallikrein and epithelial polarity in transfected Madin-Darby canine kidney cells. 749 Jan 45

We studied vascular sodium pump activity and its regulation by vasoactive agents and endothelium in cultured aortic vascular smooth muscle cells from normotensive Wistar-Kyoto rats (WKY) and spontaneously hypertensive rats (SHR). Baseline sodium pump activity (ouabain-inhibitable 86Rb+ uptake) was similar in cells from both rat strains. Angiotensin II and endothelin-1 increased ouabain-inhibitable 86Rb+ uptake more in SHR than WKY cells, whereas no effects were obtained with sodium nitroprusside, 8-bromo-cGMP, or iloprost. We examined the influence of endothelium on vascular sodium pump activity either by coculturing smooth muscle and endothelial cells or by using conditioned medium. Both coculture for 24 hours with endothelial cells and treatment with conditioned medium increased smooth muscle cell sodium pump activity, this effect being higher in SHR cells. These results suggest that the endothelium may modulate sodium pump activity in the underlying smooth muscle by releasing a diffusible compound, which is more active on SHR smooth muscle. The conditioned medium obtained in the presence of inhibitors of angiotensin-converting enzyme, endothelin-1-converting enzyme, cyclooxygenase, lipoxygenase, and nitric oxide synthase had no effect on the ability of conditioned medium to increase sodium pump activity, suggesting that angiotensin II, endothelin-1, eicosanoids, and nitric oxide are not involved in this stimulatory effect. The nature of the possible endothelial factor involved is still unknown, but it possesses a molecular weight between 25 and 50 kD, is heat stable, and is sensitive to trypsin treatment. We propose it could be a growth factor.
Hypertension 1995 Jul
PMID:Endothelial stimulation of sodium pump in cultured vascular smooth muscle. 760 21

A 68-year-old female visited our hospital because of low hemoglobin A1c content, which was found by chance at a health checkup. She did not have any symptom or sign except hypertension and low HbA1c. To determine the reason why HbA1c was so low in usual laboratory test, we carried out isoelectrofocusing (IEF) of the hemolysate, Hb instability test, and detection and isolation of the abnormal globin chain by urea CM-cellulose column chromatography. The abnormal beta-globin chain was digested with TPCK-trypsin, and the tryptic peptides were separated by HPLC on a reversed phase column. Finally the determination of amino acid composition and amino acid sequence of the abnormal peptide were performed. The Hb variant was identified as Hb Riyadh (beta 120Lys-->Asn). The detection and analysis of abnormal hemoglobin will be expected to increase in accordance with the increased opportunity of public health checkup.
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PMID:[An abnormal hemoglobin which was found by chance at a health checkup]. 767 38

The effects of single and repeated short-term (4 hr) obstruction of pancreaticobiliary duct (PBDO), with or without exocrine stimulation (intraductal hypertension) by cerulein infusion (0.2 micrograms/kg.hr), on the exocrine pancreas were evaluated in the rat. Single blockage of pancreaticobiliary duct for 4 hr caused a significant rise in serum amylase levels, pancreatic water content, and redistribution of lysosomal enzyme, cathepsin B from the lysosomal fraction to the zymogen fraction, which was considered to mean the colocalization of lysosomal enzymes with pancreatic digestive enzymes in the same subcellular compartment in acinar cells. In addition, the accelerated lysosomal and mitochondrial fragility was observed in the single pancreaticobiliary-duct-obstructed animals. Moreover, the repeated PBDO for 4 hr (2 hr in each obstruction and 1 hr of free flowing of pancreaticobiliary juice between two obstructions) caused more marked changes in almost the all parameters, and the repeated PBDO with intraductal hypertension caused an activation of trypsinogen in the pancreas, making more marked changes in almost the all parameters than the repeated PBDO only group. These results indicate that the present model of repeated PBDO with exocrine stimulation seems to be a pertinent model for gallstone pancreatitis in humans, and that redistribution of lysosomal enzymes and subcellular organellar fragility seem to play an important role in the pathogenesis of pancreatic injuries induced by PBDO, particularly by repeated PBDO with exocrine stimulation, probably via activation of trypsinogen to trypsin by lysosomal enzyme, cathepsin B.
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PMID:A possible mechanism for gallstone pancreatitis: repeated short-term pancreaticobiliary duct obstruction with exocrine stimulation in rats. 767 5


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