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)

A new inactive (latent) form of renin was found in rat brain extract. It is activated by sulfhydryl compounds such as dithiothreitol but not by proteases such as trypsin. The activated form of latent renin in crude brain extract was again inactivated by the disulfide compound sodium tetrathionate. Latent renin was separated, at least partially, from active renin by affinity chromatography on Affi-Gel Blue. In contrast to a marked (10-fold) increase of latent renin by dithiothreitol, the enzyme activity of active renin was increased by less than 50% by this sulfhydryl compound. Thus, the major part of the activating effect of dithiothreitol does not seem to be due to its effect on renin substrate. Latent renin showed affinity for pepstatin-Sepharose gel. These properties indicate that latent renin is different from inactive renin of the zymogen type, which is activated by protease or acid treatment but not by sulfhydryl compounds and does not show affinity to pepstatin. Latent renin has a molecular weight of 45,000 and is reduced to 34,000 upon activation by dithiothreitol. This observation suggests that latent renin may be a renin-inhibitor complex.
Hypertension
PMID:A new form of inactive renin in rat brain. A latent renin. 637 94

The relationship of active renin and inactive renin (trypsin-activated angiotensin-I-forming enzyme) to sodium depletion was examined in renal and peripheral plasma and at the subcellular level in the kidneys of dogs. Subcellular fractionation was carried out by discontinuous sucrose density (1.5 and 1.6 M) centrifugation. Sodium depletion selectively caused a six- to sevenfold increase in the renal content of inactive and active renins in the original homogenate, while the subcellular distribution patterns of these enzymes were little changed. Of the total granule fractions of 1.5 M sucrose (F1), 1.6 M sucrose (F2), and sediment (F3), approximately 80% of inactive renin was recovered in F1, which was rich in microsomes, while about 50% of active renin was in F2. The ratio of inactive to active renin was 0.02 in F1 and 0.003 to 0.004 in F2. Sodium depletion also caused a 20-fold increase in active renin and a twofold increase in inactive renin in peripheral plasma. The renal venous-arterial concentration difference of inactive renin was statistically significant in low-sodium dogs, although it was not significant in controls. The ratio of inactive to active renin was 0.2 to 0.4 in plasma from low-sodium dogs, while it was 1.5 to 3 in plasma from control dogs. These results suggest that plasma inactive renin originates, at least in part, in the kidney.
Hypertension
PMID:Effects of sodium depletion on inactive and active renin from dog kidney and plasma. 637 45

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

The amount and biochemical properties of renin excreted by anesthetized dogs were investigated to elucidate the significance of urinary excretion in the metabolism of renin. Mean arterial blood pressure was 127 +/- 4 mm Hg, renal blood flow was 170 +/- 8 ml/min, glomerular filtration rate, 38.6 +/- 2.3 ml/min, and urine flow rate, 0.37 +/- 0.09 ml/min (n = 11). Urinary renin concentration (URC) was 9.2 +/- 2.1 ng angiotensin I (ANG I)/ml X hr (n = 11), as determined by radioimmunoassay for ANG I generated by incubation with semipurified homologous renin substrate. The ANG I-producing activity was inhibited by more than 90% by a specific antibody to dog kidney renin. The renin secretion rate from the left kidney into the renal vein was 76.4 +/- 13.3 ng ANG I/ml X hr per min (n = 11), and the simultaneous urinary excretion rate of renin was 2.3 +/- 0.4 ng ANG I/ml X hr per min (n = 11). Molecular weight of the urinary renin was 40,000 daltons. The pH dependent curves of the angiotensin-forming capacity of renin showed an optimum between pH 5.5 to 6.0, and the estimated Michaelis constant was 0.42 microM. These biochemical parameters were similar to the findings in the case of renin in the plasma and the kidney. Moreover, neither acid nor trypsin treatment altered the renin activity in the urine. Thus, the active form of renin with a molecular weight 40,000 was excreted into the urine in dogs. Urinary excretion of renin was a small percentage of the renin secretion rate, thereby indicating the minor role of urinary excretion in the metabolism of renin.
Hypertension
PMID:Urinary excretion of renin and its biochemical properties in dogs. 639 86

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

Prokallikrein in the kidney was partially purified with immunoaffinity and DEAE Sephadex A-50 column chromatographies, and its biochemical properties were studied in comparison to three active glandular kallikreins purified from kidney, serum, and urine of the rat. The properties of the enzyme obtained by trypsin activation of prokallikrein were identical with those of active glandular kallikreins from the kidney, serum, and urine of the rat. Apparent molecular weights of prokallikrein, trypsin-activated kallikrein, active renal kallikrein, and glandular kallikrein in rat serum were 38,000 and of active urinary kallikrein, 37,000. Prokallikrein fraction was activated only by trypsin, but not by acidification, pepsin, and rat urinary esterase A treatments. Renal kallikrein, purified in the presence of soybean trypsin inhibitor (SBTI), contained 85% prokallikrein, but the enzymic fraction, purified in the absence of SBTI, contained 23% prokallikrein. Prokallikrein contents of urinary kallikrein and glandular kallikrein in rat serum were 16% and 20% respectively. These results suggest that prokallikrein is produced in the kidney and activated easily by a trypsin-like enzyme. Since rat serum contains active glandular kallikrein, kallikrein in the kidney may be secreted not only into the urine, but also into the blood.
Hypertension
PMID:Existence of prokallikrein in the kidney. Its biochemical properties compared to three active glandular kallikreins from the kidney, serum, and urine of the rat. 655 28

The present study was undertaken to evaluate the participation of the kallikrein-kinin system in the normalization of blood pressure after release of the clip in one-kidney, one clip hypertensive rats ( 1K1C ). Kininogen was determined before and after unclipping by tryptic digestion of denatured rat plasma, and spasmogenic activity was measured with isolated guinea pig ileum. In contrast to human plasma for which bradykinin (BK) is the only trypsin-releasable spasmogenic substance ( TRSS ), rat plasma contains non-BK TRSS (Fractions P1 and P2) as well as BK. Fractions P1 and P2 were separated from BK by SP-Sephadex chromatography. An increase of total TRSS was demonstrated 60 days after clipping and reached a maximum at approximately Day 75, which was two times that of the normotensive controls (NC). The level of total TRSS did not change after unclipping . The increased level of TRSS in the hypertensive state confirmed the observations of other investigators who reported increased kininogen levels but who could not distinguish between BK and non-BK TRSS because bioassays were performed without prior chromatographic separation of the spasmogenic activities. Fractions P1 and P2 were present in the TRSS of both 1K1C and NC plasma, but were two to six times higher in 1K1C and thus probably accounted quantitatively for the increased TRSS in 1K1C . The data suggest that in the hypertensive state there is an alteration in the relative amounts of some plasma proteins that contain non-BK TRSS within their amino acid sequences. Fractions P1 and P2 also contain potentiating peptides and have not yet been purified to homogeneity.(ABSTRACT TRUNCATED AT 250 WORDS)
Hypertension
PMID:Increased levels of new spasmogenic substances released by trypsin from plasma of hypertensive rats. 656 14

Normal plasma contains inactive renin, which becomes active when plasma is dialyzed to pH 3.3 and to pH 7.5, or treated with pepsin or trypsin. Under optimal conditions, each of these procedures activated the same quantity of renin, which was not further increased by repeating or combining two procedures, thus suggesting that the same pool of inactive renin was activated by each procedure. When plasma was fractionated by gel filtration, dialysis activated very little renin in eluates. Trypsin activated renin, but under some conditions also destroyed renin. Pepsin fully activated the inactive renin in eluates without evidence of destruction of renin. The pepsin-activated renin of normal plasma eluted from Sephadex G-100 in a peak of apparent molecular weight (MW) 58,000 and from Sephacryl S-200 with apparent MW 53,000, like big renin in plasma of patients with diabetic nephropathy. Inactive renin was usually increased in amount in plasma of sodium-depleted normal men, but the elution volume did not change with sodium intake. When renin was fully activated in plasma incubated with pepsin or trypsin, the apparent MW of the main peak of big renin did not change appreciably. Inactive renin in plasma was usually increased after sodium depletion, but the elution volume did not change. Active renin of normal plasma had an apparent MW near 41,000 on both gels. Thus, we conclude that big renin is present in normal plasma in amounts at least equal to and usually greater than active renin (the ratio depending on sodium intake) and that pepsin activation readily demonstrates big renin in eluates from gel filtration.
Hypertension
PMID:Inactive renin of high molecular weight (big renin) in normal human plasma. Activation by pepsin, trypsin, or dialysis to pH 3.3 and 7.5. 678 Apr 60

Rat isolated kidneys were perfused for 60 minutes with a modified Krebs-Henseleit bicarbonate solution. Perfusate and urine samples showed kininogenase activity (active kallikrein) which could be enhanced by activation with trypsin (activatable kallikrein). Identification of the kininogenase activity generated by trypsin was made with rat renal kallikrein antiserum, aprotinin, lima bean trypsin inhibitor (LBTI), soybean trypsin inhibitor (SBTI), and ovomucoid. A sample of perfusate was partially purified through DEAD-Sephacel chromatography. Intraarterial injection of this fraction decreased blood pressure in the perfused hind limb of a rat.
Hypertension
PMID:Release of activatable kallikrein by isolated rat kidneys. 691 40

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


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