The cat: an animal model for studies of inactive renin

Inactive renin, prorenin, is found in high concentrations in human plasma. We report herein the characteristics of trypsin-activated inactive renin from cat kidney and plasma. Cat and human plasma inactive renin were activated by similar concentrations of trypsin. As in humans, there was more inactive than active renin in cat plasma; also, inactive renin was low but detectable after nephrectomy. Trypsin-activated renal inactive renin, purified on Cibacron blue agarose and pepstatin-amino-hexyl-Sepharose chromatography, was inhibited by pepstatin and by a renin inhibitor similarly to cat and human active renins. The pH optimum of cat renin was biphasic: the higher peak of active renin was at pH 5.7, whereas that of activated inactive renin was at pH 7.5. As in humans, active and inactive plasma renin increased during sodium depletion and inactive renin increased during beta-adrenergic blockade, while active renin decreased. These results demonstrate that cat inactive renin is similar to human prorenin. Therefore, the cat may be a useful model for the study of prorenin.

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Measurement of inactive renin in normal, nephrectomized, and adrenalectomized rats

Canadian Journal of Physiology and Pharmacology ◽

10.1139/y91-205 ◽

1991 ◽

Vol 69 (9) ◽

pp. 1381-1384 ◽

Cited By ~ 4

Author(s):

Knud Poulsen ◽

Arne Høj Nielsen ◽

Arne Johannessen

Keyword(s):

Animal Model ◽

Exchange Resin ◽

Cation Exchange Resin ◽

Plasma Renin ◽

Rat Plasma ◽

Angiotensin I ◽

Renin Substrate ◽

Suitable Animal Model ◽

Inactive Renin ◽

Adrenalectomized Rats

In a new method for measurement of inactive rat plasma renin, the trypsin generated angiotensin I immunoreactive material, which was HPLC characterized as similar to tetradecapeptide renin substrate, is removed by a cation exchange resin before the renin incubation step. The method also corrects for trypsin destruction of endogenous angiotensinogen by the addition of exogenous angiotensinogen. When measured with this method inactive renin in rat plasma decreased after nephrectomy and increased after adrenalectomy. This is in accordance with findings in humans. A sexual dimorphism of prorenin (inactive renin) in rat plasma, similar to that reported in humans and mice, was demonstrated. Thus, inactive renin in the rat is no exception among species, and the rat might be a suitable animal model for further studies dealing with the physiology of prorenin in plasma and tissues.Key words: angiotensinogen, inactive renin, renin.

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Absence of Activation in Vitro of Renin in Rat Plasma

Clinical Science ◽

10.1042/cs0620435 ◽

1982 ◽

Vol 62 (4) ◽

pp. 435-437 ◽

Cited By ~ 5

Author(s):

M. H. De Keijzer ◽

A. P. Provoost ◽

F. H. M. Derkx

Keyword(s):

Human Plasma ◽

Active Form ◽

Plasma Renin ◽

Rat Plasma ◽

Plasma Renin Concentration ◽

Inactive Form ◽

Inactive Renin

1. Rat plasma was subjected at 4°C to various treatments known to convert inactive renin into its active form in human plasma. 2. No statistical differences in plasma renin concentration were found when the levels after the various treatments were compared with that of untreated rat plasma. 3. It is concluded that, in contrast to human plasma, no inactive form of renin is present in rat plasma.

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Two-Site Direct Immunoassay Specific for Active Renin

Clinical Chemistry ◽

10.1093/clinchem/38.10.1959 ◽

1992 ◽

Vol 38 (10) ◽

pp. 1959-1962 ◽

Cited By ~ 44

Author(s):

D Simon ◽

D J Hartmann ◽

G Badouaille ◽

G Caillot ◽

T T Guyenne ◽

...

Keyword(s):

Magnetic Beads ◽

Active Form ◽

Plasma Renin ◽

Active Plasma ◽

Immunoradiometric Assay ◽

Active Renin ◽

Human Renin ◽

Direct Immunoassay ◽

Inactive Renin ◽

Normotensive Subjects

Abstract A sensitive immunoradiometric assay, without an enzymatic step and specific for active human renin, was developed with use of two monoclonal antibodies (MAbs). In this assay system, the first MAb was coupled to magnetic beads (Magnogel); the second one, directed against the active form of the enzyme, was radiolabeled with 125I. The specificity of this assay was demonstrated in experiments measuring the active plasma renin concentration in the presence or absence of inactive renin. The assay, performed in two steps, was sensitive enough to detect 0.9 pg of renin per tube (3.5 ng/L). Intra- or interassay CVs were < 10%. Concentrations of active plasma renin measured in normotensive subjects were between 7 and 40 ng/L.

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Activity Assays and Immunoassays for Plasma Renin and Prorenin: Information Provided and Precautions Necessary for Accurate Measurement

Clinical Chemistry ◽

10.1373/clinchem.2008.118000 ◽

2009 ◽

Vol 55 (5) ◽

pp. 867-877 ◽

Cited By ~ 109

Author(s):

Duncan J Campbell ◽

Juerg Nussberger ◽

Michael Stowasser ◽

A H Jan Danser ◽

Alberto Morganti ◽

...

Keyword(s):

Plasma Renin Activity ◽

Plasma Renin ◽

Inhibitor Therapy ◽

Renin Activity ◽

Renin Inhibitor ◽

Blood Samples ◽

Hypertensive Patients ◽

Active Renin ◽

Open Conformation ◽

Background Measurement

AbstractBackground: Measurement of plasma renin is important for the clinical assessment of hypertensive patients. The most common methods for measuring plasma renin are the plasma renin activity (PRA) assay and the renin immunoassay. The clinical application of renin inhibitor therapy has thrown into focus the differences in information provided by activity assays and immunoassays for renin and prorenin measurement and has drawn attention to the need for precautions to ensure their accurate measurement.Content: Renin activity assays and immunoassays provide related but different information. Whereas activity assays measure only active renin, immunoassays measure both active and inhibited renin. Particular care must be taken in the collection and processing of blood samples and in the performance of these assays to avoid errors in renin measurement. Both activity assays and immunoassays are susceptible to renin overestimation due to prorenin activation. In addition, activity assays performed with peptidase inhibitors may overestimate the degree of inhibition of PRA by renin inhibitor therapy. Moreover, immunoassays may overestimate the reactive increase in plasma renin concentration in response to renin inhibitor therapy, owing to the inhibitor promoting conversion of prorenin to an open conformation that is recognized by renin immunoassays.Conclusions: The successful application of renin assays to patient care requires that the clinician and the clinical chemist understand the information provided by these assays and of the precautions necessary to ensure their accuracy.

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Activators of Inactive Renin (‘Prorenin’) in Human Plasma: Their Connection with Kinin Formation, Coagulation and Fibrinolysis

Clinical Science ◽

10.1042/cs057089s ◽

1979 ◽

Vol 57 (s5) ◽

pp. 89s-92s ◽

Cited By ~ 6

Author(s):

F. H. M. Derkx ◽

B. N. Bouma ◽

H. L. Tan-Tjiong ◽

M. A. D. H. Schalekamp

Keyword(s):

Human Plasma ◽

Hageman Factor ◽

Active Renin ◽

Normal Plasma ◽

Inactive Renin ◽

Fletcher Factor ◽

Free Plasma ◽

Renin Activation ◽

Dependent Pathway ◽

Proteolytic Pathways

1. Human plasma was treated at 4°C with acid, trypsin, plasmin, streptokinase, urokinase, active Hageman factor fragment (β-XIIa) and β-XIIa-activated plasma prekallikrein (Fletcher factor). The conversion of inactive into active renin (activation) was studied in normal plasma (n = 10), Hageman factor-deficient plasma (n = 2), Fletcher factor-deficient plasma (n = 1) and plasminogen-free plasma (n = 4). 2. In normal plasma inactive renin was activated at pH 7·5 after treatment at pH < 4·0; at pH 3·3 the results were the same as with trypsin. This was also the case in plasminogen-free plasma. In Hageman factor-deficient plasma and in Fletcher factor-deficient plasma, however, the quantities of renin that were activated after acidification were much smaller than with trypsin. The addition of physiological amounts of active kallikrein to pH 3·3-pretreated Hageman factor-deficient plasma caused complete activation of renin. In contrast, the addition of active Hageman factor fragment to pH 3·3-pretreated Fletcher factor-deficient plasma had little or no effect. 3. Plasmin, streptokinase-activated plasminogen and urokinase-activated plasminogen activated inactive renin in pH 4·0-pretreated normal plasma as well as in pH 4·0-pretreated Hageman factor-deficient plasma and Fletcher factor-deficient plasma. 4. It is concluded that inactive renin is activated by two separate proteolytic pathways: one pathway depends on both Hageman factor and plasma prekallikrein, and the other pathway depends on plasminogen. In the Hageman factor-dependent pathway plasma kallikrein and not Hageman factor is the major activator of inactive renin. It is assumed that pH 3·3-treatment of plasma destroys the major inhibitors of kallikrein and that pH 4·0-treatment destroys the major inhibitor of plasmin.

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Active and inactive renin in primary and secondary adrenal insufficiency and during ACTH infusion

Acta Endocrinologica ◽

10.1530/acta.0.1020265 ◽

1983 ◽

Vol 102 (2) ◽

pp. 265-270

Author(s):

Lutz Belkien ◽

Petra Exner ◽

Wolfgang Oelkers

Keyword(s):

Plasma Renin ◽

Renal Secretion ◽

Young Males ◽

Active Renin ◽

Group I ◽

Inactive Renin ◽

Group Ii ◽

Peripheral Activation ◽

The Relationship ◽

Stimulation Of

Abstract. Prolonged low-dose ACTH infusion leads to a transient stimulation of plasma renin activity (PRA) and angiotensin II. In part 1 of the present study (infusion of 10 IU of ACTH per day for 38 h into 6 normal young males), it was shown that the concentration of active renin (aPRC) increases in parallel to PRA. Thus, the rise in PRA is either due to net active renin secretion by the kidney or to increased conversion of inactive into active renin. Since the plasma concentration of inactive renin (iPRC) tended to rise rather than to fall during ACTH infusion, peripheral activation of inactive renin is probably not the cause of the rise in aPRC. Part 2 of the study consisted in the measurement of plasma ACTH, cortisol, PRA, aPRC and iPRC in 10 patients (group I) with primary adrenocortical insufficiency (8 Addisonians, 2 adrenalectomized Cushing's) and in 9 patients with hypopituitarism (group II) after short-term withdrawal of hydrocortisone substition therapy. ACTH was 1770 ± 390 pg/ml in the former and 20 ± 4 pg/ml in the latter group. PRA and aPRC were higher and the ratio iPRC:aPRC lower in group I than in group II. This might indicate stimulation of active renin formation by ACTH. However, it is unlikely that the higher aPRC levels in group I are due to increased peripheral activation of inactive renin, since the relationship between aPRC and the ratio iPRC:aPRC fell on the same curve in both groups. ACTH or an ACTH-dependent mechanism raises aPRC, probably by stimulating its renal secretion rather than by peripheral activation of inactive renin.

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Immunoradiometric Assay of Active Renin in Human Plasma: Comparison with Plasma Renin Activity

Clinical and Experimental Hypertension Part A Theory and Practice ◽

10.3109/10641968709158991 ◽

1987 ◽

Vol 9 (8-9) ◽

pp. 1383-1390 ◽

Cited By ~ 2

Author(s):

P. Dessì-fulgheri ◽

F. Cocco ◽

N. Glorioso ◽

F. Bandiera ◽

P. Madeddu ◽

...

Keyword(s):

Plasma Renin Activity ◽

Human Plasma ◽

Plasma Renin ◽

Renin Activity ◽

Immunoradiometric Assay ◽

Active Renin

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Isolation of a Renal Thiol Protease that Activates Inactive Plasma Renin

Clinical Science ◽

10.1042/cs057093s ◽

1979 ◽

Vol 57 (s5) ◽

pp. 93s-96s ◽

Cited By ~ 5

Author(s):

Eve E. Slater ◽

Anne D. Gounaris ◽

E. Haber

Keyword(s):

Human Plasma ◽

Cathepsin B ◽

Renal Cortex ◽

Plasma Renin ◽

Renin Activity ◽

Thiol Protease ◽

Inactive Renin

1. A thiol protease with properties similar to those of cathepsin B (EC 3.4.22.1) has been isolated and purified from human renal cortex. 2. This enzyme can generate renin activity from renin-suppressed and anephric human plasma at pH 5·5. 3. The renin activity thus generated is inhibited completely by antibody to purified human renal renin. This activation therefore represents the release of inactive renin.

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Two Forms of Plasma Renin after Activation In Vitro and their Relation to Natural Plasma Renin

Clinical Science ◽

10.1042/cs061295s ◽

1981 ◽

Vol 61 (s7) ◽

pp. 295s-298s ◽

Cited By ~ 2

Author(s):

F. H. M. Derkx ◽

M. P. A. Schalekamp ◽

M. A. D. H. Schalekamp

Keyword(s):

Plasma Renin ◽

The Other ◽

Clotting Factor ◽

Similar Reaction ◽

Factor Xii ◽

Ph Optimum ◽

Renin Substrate ◽

Active Renin ◽

Blue Sepharose

1. Inactive renin in human plasma can be activated by pH 3.3-dialysis (generation of acid-activated renin), by clotting factor XII-mediated prekallikrein to kallikrein conversion after pH has been restored to neutral (generation of acid-kallikrein-activated renin) or by the addition of trypsin (generation of trypsin-activated renin). 2. Natural active renin, acid-kallikrein-activated renin and trypsin-activated renin behave similarly during affinity chromatography on Blue-Sepharose CL-6B and during gel filtration on Sephadex G-100. They also show similar reaction kinetics with similar pH-optimum curves when acting on sheep renin substrate. 3. Acid-activated renin is different. It is retained on Blue-Sepharose columns and it is inactivated at neutral pH during incubation at 37°C. This contrasts with the other forms of renin activated in vitro and with natural active renin. The pH-optimum curve of acid-activated renin, when acting on sheep renin substrate, is also different from that of the other forms of active renin. 4. It is to be proven that the renins generated in vitro by neutral serine proteinases are identical with natural active renin, but clearly they bear more resemblance to natural renin than acid- activated renin does. Our preliminary conclusion is that acid-activated renin is a ‘laboratory renin’, which does not circulate in normal peripheral venous plasma.

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