Absence of Activation in Vitro of Renin in Rat Plasma

1982 ◽  
Vol 62 (4) ◽  
pp. 435-437 ◽  
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.

Activation of Inactive Plasma Renin by Plasma and Tissue Kallikreins

1979 ◽  
Vol 57 (4) ◽  
pp. 351-357 ◽  
Author(s):  
F. H. M. Derkx ◽  
H. L. Tan-Tjiong ◽  
A. J. Man In 'T Veld ◽  
M. P. A. Schalekamp ◽  
M. A. D. H. Schalekamp
Keyword(s):  
Active Form ◽  
Plasma Renin ◽  
Exchange Chromatography ◽  
Acid Activation ◽  
Ph Profile ◽  
Simultaneous Generation ◽  
Inactive Renin ◽  
Fletcher Factor

1. Normal human plasma contains a pro-activator of inactive renin. The pro-activator is activated at physiological pH in plasma that has been pretreated with acid. This activation in vitro leads to the conversion of inactive renin into the active form with simultaneous generation of kallikrein activity. 2. The endogenous activator of inactive renin has the same pH profile and inhibitor spectrum as plasma kallikrein. 3. Inactive renin can also be activated by exposure of plasma to exogenous trypsin, and in normal plasma the quantities of inactive renin that are activated after acidification and with trypsin are identical. Prekallikrein (Fletcher factor)-deficient plasma, however, has much lower renin activity after acidification than with trypsin. Thus acid activation of inactive renin depends on plasma prekallikrein, whereas the action of trypsin is independent of prekallikrein. 4. Highly purified tissue (pancreatic) kallikrein, in a concentration of less than 2 × 10−8 mol/l, activates inactive renin that has been isolated from plasma by ion-exchange chromatography. In this respect it is at least 100 times more potent than trypsin. 5. It is therefore possible that plasma and/or tissue (renal) kallikreins are also involved in the activation of inactive renin in vivo.

Effects of stimulation of renin release on trypsin-activable renin in rat plasma

1982 ◽  
Vol 243 (3) ◽  
pp. E206-E212 ◽  
Author(s):  
J. D. Barrett ◽  
P. Eggena ◽  
J. R. Sowers ◽  
M. P. Sambhi
Keyword(s):  
Plasma Renin ◽  
Rat Plasma ◽  
Assay Method ◽  
Ph Optimum ◽  
Inactive Form ◽  
Normal Rat ◽  
Inactive Renin ◽  
Arteries And Veins ◽  
Stimulation Of

Little information is available concerning inactive renin in rat plasma. A renin assay method has now been developed for measurement of active and inactive renin in approximately 0.1 ml rat plasma. Trypsin treatment of plasma (5.0 mg trypsin/ml plasma for 5 min at 0 degrees C) to maximally increase the rate of angiotensin I generation did not alter the Km or pH optimum of the renin reaction. Utilizing trypsin, 79 +/- 6% of the total renin (active + inactive) in normal rat plasma is in the inactive form. In vivo stimulation of renin by restraint stress induces a reciprocal change in active and inactive plasma plasma renin, and exposure of animals to ether elevates active and total renin, whereas inactive renin shows a small but nonstatistical decline. Although a parallel disappearance of active and inactive renin is observed after bilateral nephrectomy of the pentobarbital-anesthetized animal, complete occlusion of the renal arteries and veins after ether-induced renin stimulation results in a significant increase of inactive renin. This suggests that possibility of formation of inactive renin from the active enzyme in high renin states. These studies indicate that the balance of active and trypsin-activable renins in rat plasma may be dependent or not only the method but also the degree of in vivo renin stimulation.

Modification of glycosylation of renin in sodium-depleted and captopril-treated rats

1989 ◽  
Vol 256 (6) ◽  
pp. E798-E804 ◽  
Author(s):  
S. Kim ◽  
M. Hosoi ◽  
M. Hiruma ◽  
F. Ikemoto ◽  
K. Yamamoto
Keyword(s):  
Half Life ◽  
Blood Circulation ◽  
Relative Proportion ◽  
Plasma Renin ◽  
Rat Plasma ◽  
Con A ◽  
Plasma Renin Concentration ◽  
Rat Renal Cortical Slices ◽  
Cortical Slices

Concanavalin A (con A) chromatography of rat plasma revealed the presence of three differently glycosylated forms of renin, including the con A unbound form (renin C), the loosely bound form (renin A), and the tightly bound form (renin B). Rat renal cortical slices in vitro secreted all these forms. They had a different half-life in the plasma after ligation of both renal artery and vein (half-life of 21 +/- 1, 14 +/- 3, and 35 +/- 4 min for renin A, B, and C, respectively). Thus differently glycosylated forms of renin are released from the kidney into the blood circulation and disappear, with a different half-life. Rats were sodium-depleted and captopril-treated (40-60 mg.kg-1.day-1) for 2 wk, and the effects of these treatments on relative proportions of renin A, B, and C were investigated. These treatments elevated plasma renin concentration approximately 60-fold (from 24 +/- 3 to 1,406 +/- 128 ng angiotensin I.h-1.ml-1; P less than 0.01), in association with an increase in the relative percent of renin C in the plasma from 22 +/- 2 to 39 +/- 3% (P less than 0.01). Moreover, the relative proportion of renin C released from the renal cortical slices was significantly higher in the treated than in the control rats (42 +/- 9 vs. 16 +/- 3% of secreted renin, respectively; P less than 0.02). These results show that the predominant release of renin C, with the longest half-life (35 min) in the plasma, contributes to the increased plasma renin concentration in sodium-depleted and captopril-treated rats.

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

1991 ◽  
Vol 69 (9) ◽  
pp. 1381-1384 ◽  
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.

EXTRAHEPATIC AND EXTRARENAL RENIN INACTIVATION IN THE DOG

1974 ◽  
Vol 60 (2) ◽  
pp. 217-222
Author(s):  
R. FAGARD ◽  
E. FOSSION ◽  
M. CAMPFORTS ◽  
A. AMERY
Keyword(s):  
Blood Vessels ◽  
Pulmonary Circulation ◽  
Plasma Renin ◽  
Glass Container ◽  
Plasma Renin Concentration ◽  
Vascular Beds ◽  
Extrarenal Renin

SUMMARY It was demonstrated previously that renin disappears quickly from the circulation after nephrectomy in the hepatectomized dog. In the present study the plasma renin concentration (PRC) was measured in the efferent and afferent blood vessels of several vascular beds (pulmonary circulation, splanchnic region, spleen, both inferior limbs and pelvis, head) in the anhepatic and in the anhepatic and anephric dog in order to investigate extrarenal and extrahepatic renin inactivation. However, no significant arteriovenous differences in PRC could be traced. The blood of these dogs kept in vitro at 37 °C in a glass container showed no decline in PRC within 3 h of removal. Therefore no specific extrahepatic and extrarenal renin-inactivating mechanism was found which could explain the rapid disappearance of renin from the blood in vivo in the anhepatic and anephric dog.

In Vitro Generation of Inactive Renin in Hypertensive Human Plasma

1982 ◽  
Vol 4 (11-12) ◽  
pp. 2177-2184
Author(s):  
J. D. Barrett ◽  
P. Eggena ◽  
M. S. Golub ◽  
M. P. Sambhi
Keyword(s):  
Human Plasma ◽  
Inactive Renin

THE PROTECTIVE EFFECT OF ACYLATI0N ON THE STABILITY OF EMINASE (APSAC) IN HUMAN PLASMA

1987 ◽  
Author(s):  
R Fears ◽  
H Ferres ◽  
R Standring
Keyword(s):  
Protective Effect ◽  
Human Plasma ◽  
Fibrinolytic Activity ◽  
Animal Studies ◽  
Active Form ◽  
Α2 Macroglobulin ◽  
The Stability ◽  
High Level ◽  
Activator Complex

Clinical and animal studies indicate that APSAC (anisoylated plasminogen.streptokinase activator complex, Eminase) circulates longer in the bloodstream in an active form than the other thrombolytics. In the present studies in vitro u/e have found that functional activity of APSAC is maintained in human plasma longer than that of SK.plasmin(ogen): the relative stability half-lives are similar to the plasma clearance haif-lives in patients. Some of the loss of activity of SK at early times can be attributed to neutralisation by inhibitors. Thus, the survival of fibrinolytically-active SK was promoted in plasma depleted in α2-antiplasmin (α2AP) and α2AP-SK.plasmin complexes (detected by immunoblotting) formed rapidly in normal plasma. Corresponding studies with α2 macroglobulin-depleted plasma suggested a slight, late influence on SK activity but the inhibitor complex has not been detected unequivocally. In addition, loss of SK activity can be attributed, in part, to. rapid degradation to low molecular products. The degradation of SK in APSAC was much slower. In other comparative studies, the stability of APSAC was found to be similar to the stability of prourokinase and much superior to that of SK which is similar to UK; t-PA is intermediate in stability.Maintenance of fibrinolytic activity vivo depends on the stability of the thrombolytic, its rate of clearance and mode of administration. The protective effect of acylation, demonstrated in these experiments, explains why the objective of maintaining a high level of fibrinolytic activity after intravenous bolus injection of APSAC is less compromised by opposing inactivation processes.

Two-Site Direct Immunoassay Specific for Active Renin

1992 ◽  
Vol 38 (10) ◽  
pp. 1959-1962 ◽  
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.

Specificity of mammalian kallidinogen

1964 ◽  
Vol 207 (4) ◽  
pp. 901-905 ◽  
Author(s):  
J. C. Fasciolo ◽  
K. Halvorsen
Keyword(s):  
Blood Pressure ◽  
Pressure Drop ◽  
Guinea Pig ◽  
Human Plasma ◽  
In Vitro Release ◽  
Rat Plasma ◽  
Vitro Release

Hog pancreas kallikrein does not cause a blood pressure drop in the rat, but lowers the blood pressure in the dog. Since this lack of effect could be due to the inability of hog pancreas kallikrein to act upon rat plasma, the in vitro release of kallidin with the plasma of different species was studied. Human, dog, swine, rat, guinea pig, and ox plasmas were incubated for different periods of time with hog pancreas kallikrein, and the bradykininogen (kallidinogen) consumed and the kallidin released were measured. It was found that hog pancreas kallikrein does not release any kallidin with rat and guinea pig plasma; it releases small amounts with pig plasma and greater amounts with bovine, dog, and human plasma. The bradykininogen consumption showed the same sequence.

In Vitro Evaluation of Apixaban, a Novel, Potent, Selective and Orally Bioavailable Factor Xa Inhibitor.

Blood ◽  
2006 ◽  
Vol 108 (11) ◽  
pp. 4130-4130 ◽  
Author(s):  
Joseph M. Luettgen ◽  
Tracy A. Bozarth ◽  
Jeffrey M. Bozarth ◽  
Frank A. Barbera ◽  
Patrick Y. Lam ◽  
...  
Keyword(s):  
Human Plasma ◽  
Serine Proteases ◽  
Anticoagulant Activity ◽  
Factor Xa ◽  
Coagulation Factor ◽  
Competitive Inhibitor ◽  
Rat Plasma ◽  
Reversible Inhibitor ◽  
Antithrombotic Agent

Abstract Apixaban, previously known as BMS-562247, is a high affinity, highly selective, orally-active, reversible inhibitor of coagulation factor Xa (fXa), in clinical studies as a therapeutic agent for prevention and treatment of thromboembolic diseases. The in vitro characteristics of apixaban were evaluated in purified systems and in human blood from healthy volunteers. Detailed kinetic analysis of apixaban inhibition of human fXa showed that it is a readily reversible, potent and competitive inhibitor versus a synthetic tripeptide substrate with a Ki of 0.08 nM, an association rate of 2 × 107 M−1s−1and a dissociation half life of 3.4 min. Weak affinity (Ki ~3 μM) is observed for thrombin, plasma kallikrein, and chymotrypsin. Affinity for trypsin and all other serine proteases tested is negligible with Ki > 15 μM. Apixaban is an effective inhibitor of free fXa and of prothrombinase, in buffer, platelet poor plasma, and whole blood. The anticoagulant activity of apixaban was determined in platelet-poor human plasma. Apixaban causes concentration dependent prolongation of the fXa mediated clotting assays. The human plasma concentration required to produce a doubling of the clotting time is 3.6 μM for prothrombin time, 7.4 μM for activated partial thromboplastin time and 0.4 μM for HepTest. To support preclinical efficacy and safety studies purified fXa from rabbit, dog and rat plasma was also found to be inhibited by apixaban (0.17, 2.6, and 1.3 nM, respectively). In summary the in vitro properties of apixaban show that it is a highly selective and potentially potent antithrombotic agent for venous and arterial thrombotic diseases.

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