Aggression-Provoked Renin Release from An Unknown Source in Male Mice

1981 ◽  
Vol 61 (s7) ◽  
pp. 257s-259s ◽  
Author(s):  
K. Poulsen ◽  
E. B. Pedersen
Keyword(s):  
De Novo ◽  
Plasma Renin ◽  
Fold Increase ◽  
Acid Proteinase ◽  
Male Mice ◽  
Angiotensin I ◽  
Submaxillary Glands ◽  
Specific Enzymatic Activity ◽  
Inactive Renin

1. An 800-fold increase in plasma renin occurs after aggressive behaviour in male mice without kidneys and submaxillary glands. 2. The aggression-provoked renin fulfils all the criteria so far studied for being identical with renin. 3. It is an acid proteinase which generates angiotensin I with the same Km and specific enzymatic activity as pure submaxillary renin and normal plasma renin. 4. It is immunologically identical with submaxillary renin in the direct renin assay and in crossed immunoelectrophoresis. 5. It is present in plasma as fully enzymatically active 40 000-mol. wt. renin. 6. It is not likely that it arises from an inactive precursor or binding protein in plasma, since there is no inactive renin present and the high-molecular-weight forms of renin are also present after the fighting. 7. None of many organs so far studied can account for the release. 8. Synthesis of renin de novo during fighting is not likely since it is released also after blockade in vivo of protein synthesis. 9. Origin of the renin is unknown.

Characterization of Aggression-Provoked Renin from An Unknown Source in Male Mice

1981 ◽  
Vol 61 (4) ◽  
pp. 373-378 ◽  
Author(s):  
K. Poulsen ◽  
E. B. Pedersen
Keyword(s):  
Enzymatic Activity ◽  
Control Level ◽  
Plasma Renin ◽  
Fold Increase ◽  
Male Mice ◽  
Angiotensin I ◽  
Renin Substrate ◽  
Specific Enzymatic Activity ◽  
Aspartate Proteinase

1. In male mice without kidneys and submaxillary, as well as sublingual, glands aggressive behaviour causes a vast release of renin [J. Bing & K. Poulsen (1979) Acta Physiologica Scandinavica, 107, 251–256]. 2. This resulted in about an 800-fold increase in plasma renin concentration from the control level of 0.52 (range 0.15-0.8) Goldblatt unit (G.U.) × 10−3/ml to 430 (range 300–500) G.U. × 10−3/ml after aggression. 3. The aggression-provoked renin fulfil all the criteria so far studied for being active renin, identical with normal mouse plasma renin and pure submaxillary mouse renin. 4. It generates angiotensin I with renin substrate and Km (1.2 μmol/l) is the same. It is neutralized by pepstatin but not by inhibitors of metallo-, thiol and serine proteinases, indicating that it is an aspartate proteinase (acidic proteinase). 5. It is a 40 000-mol.wt. renin, which has full enzymatic activity with a specific enzymatic activity of 0.32 G.U./μg, identical with that of normal plasma renin. 6. Its enzymatic activity is neutralized by a specific antibody against pure submaxillary renin. It is measurable in the direct renin radioimmunoassay with a dilution curve which parallels that of the standards. It demonstrates complete antigenic identity with pure submaxillary renin in crossed immunoelectrophoresis. 7. Its origin is unknown.

BIOLOGICAL SIGNIFICANCE OF ACTIVE AND INACTIVE RENIN IN MAN

1980 ◽  
Vol 85 (1) ◽  
pp. 137-143 ◽  
Author(s):  
P. LIJNEN ◽  
A. AMERY ◽  
R. FAGARD ◽  
L. VERSCHUEREN
Keyword(s):  
Plasma Concentrations ◽  
Biological Significance ◽  
Plasma Renin ◽  
Angiotensin I ◽  
Vitro Assay ◽  
Arterial Blood ◽  
Inactive Renin ◽  
Change In Mean

SUMMARY The biological significance of active and inactive renin was investigated by comparison of an in-vitro assay of active, total and inactive plasma renin concentration (PRC), plasma renin activity (PRA) and plasma concentrations of angiotensin I and II with an in-vivo change in mean arterial blood pressure (MAP) produced by antagonism of angiotensin with treatment with saralasin and by blockade of angiotensin-converting enzyme by treatment with captopril. A significant relationship between the changes in MAP during treatment with saralasin and captopril with the pretreatment levels of PRA, active and total PRC and angiotensin II were found; while the pre-existing level of inactive renin was not a predictor for the hypotensive effect of saralasin and captopril. During treatment with saralasin and captopril significant increases in PRA, plasma angiotensin I concentration and total and active PRC were found and no change in inactive PRC was observed.

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.

Angiotensin II overflow from canine skeletal muscle in vivo: importance of plasma angiotensin I

1994 ◽  
Vol 266 (5) ◽  
pp. R1664-R1669 ◽  
Author(s):  
J. H. Schwieler ◽  
J. Nussberger ◽  
T. Kahan ◽  
P. Hjemdahl
Keyword(s):  
De Novo ◽  
Ex Vivo ◽  
Plasma Renin ◽  
Gracilis Muscle ◽  
Ang Ii ◽  
Concentration Difference ◽  
Beta Adrenoceptor ◽  
Arterial Blood ◽  
Catheter System

The overflows (i.e., veno-arterial concentration differences multiplied by plasma flow) of angiotensin-(1-10) decapeptide (ANG I) and angiotensin-(1-8) octapeptide (ANG II) from blood-perfused canine gracilis muscle in situ were studied. Special precautions were taken to minimized ex vivo generation and/or degradation of angiotensins in the sampled blood. ANG I was found to be generated in the catheter system supplying the gracilis muscle with arterial blood, but plasma renin activity and ANG II levels were uninfluenced by the catheter system. A positive venoarterial concentration difference over the muscle itself was found for ANG II but not for ANG I under basal conditions. Isoprenaline elicited vasodilatation, reduced ANG I overflow, and tended to increase ANG II overflow, whereas beta-adrenoceptor blockade by propranolol had no effect on these variables. In conclusion, we found no evidence for a local de novo synthesis of ANG II from the gracilis muscle vasculature in vivo. The net overflow of ANG II was most likely caused by local conversion in the tissue of ANG I artifactually generated in the arterial catheter system. beta-Adrenoceptor stimulation enhanced the local conversion of ANG I to ANG II, probably by exposing a greater endothelial surface containing angiotensin-converting enzyme activity.

Enzymatic Activity of Renin in Plasma of Normal and Uraemic Subjects

1984 ◽  
Vol 67 (3) ◽  
pp. 365-368 ◽  
Author(s):  
Theodore A. Kotchen ◽  
Tam T. Guyenne ◽  
Pierre Corvol ◽  
Joel Menard
Keyword(s):  
Renal Failure ◽  
Enzymatic Activity ◽  
Plasma Renin ◽  
Normal Subjects ◽  
Renin Activity ◽  
Angiotensin I ◽  
Renin Substrate ◽  
Inactive Renin ◽  
Substrate Concentrations

1. Plasma renin reactivity (PRR) is the rate of angiotensin I production after addition of renin to plasma, minus endogenous renin activity. PRR is increased in plasma of patients with renal failure compared with that of normal subjects. The present study was carried out to determine if increased PRR in uraemic plasma is related to differences of endogenous active or inactive renin, endogenous renin substrate, or pH of the incubation in vitro. 2. PRR in plasma of ten uraemic patients was greater (P<0.02) than that in plasma of ten normal subjects in incubations carried out at pH 7.4 and 5.7. 3. Increased PRR was not accounted for by differences of endogenous active and inactive renin activity. 4. After addition of renin, renin concentration (measured by direct radioimmunoassay) did not differ in normal and uraemic plasma. 5. Renin substrate concentration, measured both indirectly and by direct radioimmunoassay, also did not differ in normal and uraemic plasma. 6. Increased PRR in uraemic plasma is not related to alterations of renin or renin substrate concentrations. These observations are consistent with our earlier hypothesis that there is a deficiency of a renin inhibitor in uraemic plasma.

scholarly journals Methotrexate Increases Skeletal Muscle GLUT4 Expression and Improves Metabolic Control in Experimental Diabetes

2012 ◽  
Vol 2012 ◽  
pp. 1-7 ◽  
Author(s):  
Giuseppina T. Russo ◽  
Letteria Minutoli ◽  
Alessandra Bitto ◽  
Domenica Altavilla ◽  
Eugenio Alessi ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Metabolic Control ◽  
Glucose Transporter ◽  
De Novo ◽  
Fold Increase ◽  
Low Doses ◽  
Glucose Levels ◽  
Glut4 Expression ◽  
Experimental Type

Long-term administration of 5-aminoimidazole-4-carboxamide ribonucleoside (AICAR) mimics the effects of endurance exercise by activating AMP kinase and by increasing skeletal muscle expression of GLUT4 glucose transporter. AICAR is an intermediate in the purinede novosynthesis, and its tissue concentrations can be increased,in vivo, by low doses of methotrexate (MTX) through the inhibition of the enzyme AICAR transformylase. We report here the first evidence that, in experimental type 2 diabetes, chronic treatment with low doses of MTX increases skeletal muscle GLUT4 expression and improves metabolic control. MTX (0.5 mg/kg body weight) or vehicle was administered intraperitoneally, once a week for 4 weeks, to genetically diabetic female C57BL/KsJ-m+/+Leptdbmice (db+/db+) and their normoglycemic littermates (db+/+m). In thedb+/db+mice, MTX treatment was associated with a ∼2-fold increase in skeletal muscle GLUT4 protein concentration and a >4-fold increase in GLUT4 mRNA expression (P<0.01, all), as compared to vehicle-treated mice; no significant differences were noted in controls. MTX treatment was also associated with a significant reduction of glucose and insulin serum concentrations in diabetic mice (P<0.001), and glucose levels only (P<0.05) in controls. These data indicate a different route to increase skeletal muscle GLUT4 expression, through the potential inhibition of the enzyme AICAR transformylase.

scholarly journals Analysis of lines of mice selected for fat content: 3. Flux through the de novo lipid synthesis pathway

1991 ◽  
Vol 58 (2) ◽  
pp. 123-127 ◽  
Author(s):  
Emmanuel A. Asante ◽  
William G. Hill ◽  
Grahame Bulfield
Keyword(s):  
Fatty Acid ◽  
Fatty Acid Synthesis ◽  
De Novo ◽  
Lipid Synthesis ◽  
Fold Increase ◽  
Acid Synthesis ◽  
Fat Content ◽  
Direct Selection ◽  
Lean Line

SummaryThe flux through the de novo fatty acid synthesis pathway was estimated in lines of mice which differed substantially in fat content following 26 generations of selection at 10 weeks of age. Previous estimates of lipogenic enzyme activities had indicated an increase in the capacity for lipogenesis in the Fat compared to the Lean line. Therefore the in vivo flux in lipogenesis was measured in both liver and gonadal fat pad (GFP) tissues of males at 5 and 10 weeks of age, using the rat of incorporation of 3H from 3H2O and 14C from acetate and citra te into total lipids. AT both ages and in both tissues the Fat line had a higher flux, about 20% increase in the liver and up to three-fold increase (range 1·2- to 3·4-fold) in the GFP. We conclude that direct selection for fatness in mice has resulted in metabolic changes in the ratio of de novo fatty acid synthesis, and that the changes are largely detectable before 10 weeks, the age of selection.

In vivo production of plasma angiotensin I: is plasma renin sufficient?

1989 ◽  
Vol 7 ◽  
pp. S222-223 ◽  
Author(s):  
Peter J. J. Admiraal ◽  
Frans H. M. Derkx ◽  
A. M. Jan Danser ◽  
Maarten A. D. H. Schalekamp
Keyword(s):  
Plasma Renin ◽  
Angiotensin I ◽  
Plasma Angiotensin

scholarly journals Elevated Steroidogenesis, Defective Reproductive Organs, and Infertility in Transgenic Male Mice Overexpressing Human Chorionic Gonadotropin

Endocrinology ◽  
2003 ◽  
Vol 144 (11) ◽  
pp. 4980-4990 ◽  
Author(s):  
Susana B. Rulli ◽  
Petteri Ahtiainen ◽  
Sari Mäkelä ◽  
Jorma Toppari ◽  
Matti Poutanen ◽  
...  
Keyword(s):  
Chorionic Gonadotropin ◽  
Human Chorionic Gonadotropin ◽  
Fusion Gene ◽  
Direct Action ◽  
Fold Increase ◽  
Reproductive Organs ◽  
Seminiferous Tubules ◽  
Male Mice ◽  
Α Subunit

Abstract We previously developed a transgenic (TG) mouse model that overexpresses the human chorionic gonadotropin (hCG) β-subunit under the universal human ubiquitin C promoter, displaying in males a modest 3-fold increase in circulating levels of LH/hCG bioactivity. The males were fertile and presented with a mild reproductive phenotype. To achieve higher levels of hCG, a double TG model was generated by cross-breeding the hCGβ-expressing mice with another TG line harboring a ubiquitin C/common α-subunit fusion gene. The double-TG mice expressed excessive levels of dimeric hCG, with 2000-fold elevated circulating LH/hCG bioactivity. These male mice were infertile, primarily due to inability to copulate, and they showed enhanced testicular androgen production despite clear down-regulation of LH/hCG receptors. Their intratesticular inhibin B was unaltered, but serum FSH was markedly reduced. Apparently the chronic hCG hyperstimulation led to focal Leydig cell proliferation/hypertrophy at 6 months of age, but failed to promote testicular tumors. Even though full spermatogenesis occurred in most of the seminiferous tubules, progressive tubule degeneration was apparent as the males grew older. The prostate and seminal vesicles were enlarged by distension of glandular lumina. Functional urethral obstruction was indicated by distension and sperm accumulation in distal vas deferens as well as by dilated urinary bladder and enlarged kidneys. The abnormal function of accessory sex glands and/or lower urinary tract as a consequence of the disturbed sex hormone balance or direct action of hCG may be the main cause of infertility in this model. The present study provides in vivo evidence that exposure of male mice to chronically elevated levels of hCG severely affects their urogenital tract function at multiple sites and causes infertility, but, unlike in LH/hCG overexpressing female mice, it is not tumorigenic.

scholarly journals Inhibition of Nur77/Nurr1 leads to inefficient clonal deletion of self-reactive T cells.

1996 ◽  
Vol 183 (4) ◽  
pp. 1879-1892 ◽  
Author(s):  
T Zhou ◽  
J Cheng ◽  
P Yang ◽  
Z Wang ◽  
C Liu ◽  
...  
Keyword(s):  
T Cells ◽  
T Cell ◽  
Dna Binding ◽  
Binding Proteins ◽  
Fold Increase ◽  
Dna Binding Proteins ◽  
Male Mice ◽  
Clonal Deletion ◽  
Alpha Beta

The Nur77/Nurr1 family of DNA binding proteins has been reported to be required for the signal transduction of CD3/T cell receptor (TCR)-mediated apoptosis in T cell hybridomas. To determine the role of this family of DNA-binding proteins in thymic clonal deletion, transgenic (Tg) mice bearing a dominant negative mutation were produced. The transgene consisted of a truncated Nur77 (deltaNur77) gene encoding the DNA-binding domain of Nur77 ligated to a TCR-beta enhancer resulting in early expression in thymocytes. Apoptosis of CD4+CD8+ thymocytes mediated by CD3/TCR signaling was greatly inhibited in the deltaNur77 Tg mice, compared with non-Tg littermates, after treatment with anti-CD3 or anti-TCR antibody in vivo and in vitro. Clonal deletion of self-reactive T cells was investigated in deltaNur77-Db/HY TCR-alpha/beta double Tg mice. There was a five-fold increase in the total number of thymocytes expressing self-reactive Db/HY TCR-alpha/beta in the deltaNur77-TCR-alpha/beta double Tg male mice. Deficient clonal deletion of self-reactive thymocytes was demonstrated by a 10-fold increase in the CD4+CD8+ thymocytes that expressed Tg TCR-alpha/beta. There was an eightfold increase in the CD8+, Db/HY TCR-alpha/beta T cells in the lymph nodes (LN) of delta Nur77-Db/HY TCR-alpha/beta double Tg compared with Db/HY TCR-alpha/beta Tg male mice. In spite of defective clonal deletion, the T cells expressing the Tg TCR were functionally anergic. In vivo analysis revealed increased activation and apoptosis of T cells associated with increased expression of Fas and Fas ligand in LN of deltaNur77-Db/HY TCR-alpha/beta double male mice. These results indicate that inhibition of Nur77/Nurr1 DNA binding in T cells leads to inefficient thymic clonal deletion, but T cell tolerance is maintained by Fas-dependent clonal deletion in LN and spleen.

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