scholarly journals Impact of cadmium on the level of hepatic metallothioneins, essential elements, and selected enzymes in the experimental rat model

2014 ◽  
Vol 59 (No. 12) ◽  
pp. 548-556 ◽  
Author(s):  
J. Zídková ◽  
M. Melčová ◽  
K. Bartošová ◽  
I. Šestáková ◽  
V. Zídek ◽  
...  
Keyword(s):  
Enzymatic Activity ◽  
Spontaneously Hypertensive Rat ◽  
Essential Elements ◽  
Brown Norway ◽  
Glutathione S Transferase ◽  
Spontaneously Hypertensive ◽  
Laboratory Rats ◽  
Model Study ◽  
Specific Enzymatic Activity ◽  
Different Strains

The response of different strains of laboratory rats (Rattus norvegicus L.) on both acute (via intraperitoneal injection) and chronic (via drinking water and/or diet) cadmium intoxication was investigated in the model study. The rat strains Long Evans (LE), Spontaneously hypertensive rat (SHR), and Brown Norway (BN) were tested and compared, and total Cd levels and metallothionein (MT) concentrations were determined in the liver of experimental animals. The liver MT concentrations were determined by using adsorptive chronopotentiometry and modified Brdička reaction and were significantly correlated (r = 0.965) with the total liver Cd content. Moreover, the Cd application resulted in increasing zinc liver contents confirming intensive MT synthesis in the rat liver. In the blood plasma, specific enzymatic activity of glutathione reductase (GR) and glutathione-S-transferase (GST) was determined suggesting increasing activity of GR with the amount of applied Cd for all three strains, whereas ambiguous results have been found for the activity of GST. Therefore, MT concentrations seemed to be more sensitive indicators of the Cd intoxication compared to the assessment of the specific enzymatic activity.  

scholarly journals Effects of Transgenic Expression of Dopamine Beta Hydroxylase (Dbh) Gene on Blood Pressure in Spontaneously Hypertensive Rats

2016 ◽  
pp. 1039-1044
Author(s):  
M. PRAVENEC ◽  
V. LANDA ◽  
V. ZÍDEK ◽  
P. MLEJNEK ◽  
J. ŠILHAVÝ ◽  
...  
Keyword(s):  
Blood Pressure ◽  
Essential Hypertension ◽  
Spontaneously Hypertensive Rat ◽  
Reduce Blood Pressure ◽  
Left Ventricular ◽  
Brown Norway ◽  
Catecholamine Metabolism ◽  
Mrna Levels ◽  
Spontaneously Hypertensive ◽  
Dopamine Beta Hydroxylase

The spontaneously hypertensive rat (SHR) is the most widely used animal model of essential hypertension and left ventricular hypertrophy. Catecholamines play an important role in the pathogenesis of both essential hypertension in humans and in the SHR. Recently, we obtained evidence that the SHR harbors a variant in the gene for dopamine beta hydroxylase (Dbh) that is associated with reduced adrenal expression of Dbh mRNA and reduced DBH enzymatic activity which correlated negatively with blood pressure. In the current study, we used a transgenic experiment to test the hypothesis that reduced Dbh expression predisposes the SHR to hypertension and that augmentation of Dbh expression would reduce blood pressure. We derived 2 new transgenic SHR-Dbh lines expressing Dbh cDNA under control of the Brown Norway (BN) wild type promoter. We found modestly increased adrenal expression of Dbh in transgenic rats versus SHR non-transgenic controls that was associated with reduced adrenal levels of dopamine and increased plasma levels of norepinephrine and epinephrine. The observed changes in catecholamine metabolism were associated with increased blood pressure and left ventricular mass in both transgenic lines. We did not observe any consistent changes in brainstem levels of catecholamines or of mRNA levels of Dbh in the transgenic strains. Contrary to our initial expections, these findings are consistent with the possibility that genetically determined decreases in adrenal expression and activity of DBH do not represent primary determinants of increased blood pressure in the SHR model.

Genetic variation in photoperiodism among naturally photoperiodic rat strains

2001 ◽  
Vol 281 (6) ◽  
pp. R1817-R1824 ◽  
Author(s):  
Annaka M. Lorincz ◽  
M. Benjamin Shoemaker ◽  
Paul D. Heideman
Keyword(s):  
Somatic Growth ◽  
Brown Norway ◽  
Testis Size ◽  
Young Males ◽  
Laboratory Rats ◽  
Fischer 344 ◽  
Critical Photoperiod ◽  
Photoperiodic Responses ◽  
Different Strains ◽  
Long Photoperiod

Rattus norvegicus has been considered nonphotoperiodic, but Fischer 344 (F344) rats are inhibited in growth and reproductive development by short photoperiod (SD). We tested photoresponsiveness of the genetically divergent Brown Norway (BN) strain of rats. Peripubertal males were tested in long photoperiod or SD, with or without 30% food reduction. Young males were photoresponsive, with reductions in testis size, body mass, and food intake in SD and with enhanced responses to SD when food restricted. Photoperiods ≤11 h of light inhibited reproductive maturation and somatic growth, whereas photoperiods of 12 h or more produced little or no response. F344/BN hybrids differ from both parent strains in the timing, amplitude, and critical photoperiod of photoperiodic responses, indicating genetic differences in photoperiodism between these strains. This is consistent with the hypothesis that ancestors of laboratory rats were genetically variable for photoperiodism and that different combinations of alleles for photoperiodism have been fixed in different strains of rats.

scholarly journals Integrated genomic approaches to identification of candidate genes underlying metabolic and cardiovascular phenotypes in the spontaneously hypertensive rat

2011 ◽  
Vol 43 (21) ◽  
pp. 1207-1218 ◽  
Author(s):  
Catherine Morrissey ◽  
Ian C. Grieve ◽  
Matthias Heinig ◽  
Santosh Atanur ◽  
Enrico Petretto ◽  
...  
Keyword(s):  
Quantitative Trait ◽  
Protein Function ◽  
Genomic Sequence ◽  
Spontaneously Hypertensive Rat ◽  
Transcript Abundance ◽  
Brown Norway ◽  
Nucleotide Polymorphisms ◽  
Susceptibility Loci ◽  
Spontaneously Hypertensive ◽  
Hypertensive Rat

The spontaneously hypertensive rat (SHR) is a widely used rodent model of hypertension and metabolic syndrome. Previously we identified thousands of cis-regulated expression quantitative trait loci (eQTLs) across multiple tissues using a panel of rat recombinant inbred (RI) strains derived from Brown Norway and SHR progenitors. These cis-eQTLs represent potential susceptibility loci underlying physiological and pathophysiological traits manifested in SHR. We have prioritized 60 cis-eQTLs and confirmed differential expression between the parental strains by quantitative PCR in 43 (72%) of the eQTL transcripts. Quantitative trait transcript (QTT) analysis in the RI strains showed highly significant correlation between cis-eQTL transcript abundance and clinically relevant traits such as systolic blood pressure and blood glucose, with the physical location of a subset of the cis-eQTLs colocalizing with “physiological” QTLs (pQTLs) for these same traits. These colocalizing correlated cis-eQTLs (c3-eQTLs) are highly attractive as primary susceptibility loci for the colocalizing pQTLs. Furthermore, sequence analysis of the c3-eQTL genes identified single nucleotide polymorphisms (SNPs) that are predicted to affect transcription factor binding affinity, splicing and protein function. These SNPs, which potentially alter transcript abundance and stability, represent strong candidate factors underlying not just eQTL expression phenotypes, but also the correlated metabolic and physiological traits. In conclusion, by integration of genomic sequence, eQTL and QTT datasets we have identified several genes that are strong positional candidates for pathophysiological traits observed in the SHR strain. These findings provide a basis for the functional testing and ultimate elucidation of the molecular basis of these metabolic and cardiovascular phenotypes.

scholarly journals Spontaneously hypertensive rat: cholera toxin converts suppression to immunity through a Th2 cell-IL-4 pathway

1997 ◽  
Vol 273 (4) ◽  
pp. R1509-R1518 ◽  
Author(s):  
David W. Pascual ◽  
Michel Coste ◽  
Prosper N. Boyaka ◽  
Hiroshi Kiyono ◽  
Jerry R. McGhee
Keyword(s):  
T Cells ◽  
T Cell ◽  
Cholera Toxin ◽  
Spontaneously Hypertensive Rat ◽  
Brown Norway ◽  
No Production ◽  
Antibody Treatment ◽  
Spontaneously Hypertensive ◽  
Hypertensive Rat ◽  
Ifn Γ

The spontaneously hypertensive rat (SHR) exhibits a number of T cell dysfunctions that develop concurrently with elevated blood pressure. Studies have shown a mitogen-induced lymphocyte suppression mediated in part by the production of interferon-γ (IFN-γ), which stimulated NO production by macrophages. To assess whether this immune suppression is reversible, SHR were immunized with diphtheria toxoid (DT) with or without cholera toxin (CT) as adjuvant. SHR immunized with DT only displayed weak serum immunoglobulin G (IgG) anti-DT titers, tenfold less than similarly treated normotensive Wistar-Kyoto rats (WKYR). SHR CD4+T cells failed to proliferate upon in vitro stimulation with DT. In contrast, SHR coimmunized with DT and CT showed serum IgG antibody titers similar to WKYR and Brown Norway rats. Coimmunization with CT rescued SHR CD4+T cells from suppression and supported DT- or B subunit of CT-specific proliferative responses, and these cells produced more interleukin-4 (IL-4) than IFN-γ, and anti-IFN-γ antibody treatment enhanced IL-4 production. Exogenous IL-4 increased the proliferation of antigen-specific CD4+T cells, whereas IFN-γ was inhibitory. This study shows that the adjuvant CT induces T helper 2-type responses, reversing the T cell dysfunction in the SHR.

Congenic strains provide evidence that four mapped loci in chromosomes 2, 4, and 16 influence hypertension in the SHR

2009 ◽  
Vol 37 (1) ◽  
pp. 52-57 ◽  
Author(s):  
Ivy Aneas ◽  
Mariliza V. Rodrigues ◽  
Bianca A. Pauletti ◽  
Gustavo J. J. Silva ◽  
Renata Carmona ◽  
...  
Keyword(s):  
Salt Intake ◽  
Spontaneously Hypertensive Rat ◽  
High Salt ◽  
Brown Norway ◽  
Chromosome 4 ◽  
Chromosome 16 ◽  
Salt Loading ◽  
Norway Rat ◽  
Spontaneously Hypertensive ◽  
High Salt Intake

To dissect the genetic architecture controlling blood pressure (BP) regulation in the spontaneously hypertensive rat (SHR) we derived congenic rat strains for four previously mapped BP quantitative trait loci (QTLs) in chromosomes 2, 4, and 16. Target chromosomal regions from the Brown Norway rat (BN) averaging 13–29 cM were introgressed by marker-assisted breeding onto the SHR genome in 12 or 13 generations. Under normal salt intake, QTLs on chromosomes 2a, 2c, and 4 were associated with significant changes in systolic BP (13, 20, and 15 mmHg, respectively), whereas the QTL on chromosome 16 had no measurable effect. On high salt intake (1% NaCl in drinking water for 2 wk), the chromosome 16 QTL had a marked impact on SBP, as did the QTLs on chromosome 2a and 2c (18, 17, and 19 mmHg, respectively), but not the QTL on chromosome 4. Thus these four QTLs affected BP phenotypes differently: 1) in the presence of high salt intake (chromosome 16), 2) only associated with normal salt intake (chromosome 4), and 3) regardless of salt intake (chromosome 2c and 2a). Moreover, salt sensitivity was abrogated in congenics SHR.BN2a and SHR.BN16. Finally, we provide evidence for the influence of genetic background on the expression of the mapped QTLs individually or as a group. Collectively, these data reveal previously unsuspected nuances of the physiological roles of each of the four mapped BP QTLs in the SHR under basal and/or salt loading conditions unforeseen by the analysis of the F2 cross.

Renal renin activity is associated with alterations of the renin gene in recombinant inbred rat strains

1993 ◽  
Vol 84 (2) ◽  
pp. 129-132 ◽  
Author(s):  
Irena Pohlová ◽  
Josef Zicha ◽  
Vladimir Křen ◽  
Jaroslav Kuneš ◽  
Michal Pravenec
Keyword(s):  
Blood Pressure ◽  
Recombinant Inbred ◽  
Spontaneously Hypertensive Rat ◽  
Inbred Strains ◽  
Renin Activity ◽  
Recombinant Inbred Strains ◽  
Brown Norway ◽  
Spontaneously Hypertensive ◽  
Hypertensive Rat ◽  
Renin Gene

1. A structural alteration within the first intron of the renin gene in spontaneously hypertensive rats was demonstrated to co-segregate with blood pressure in some sets of F2 hybrids or recombinant inbred strains. There is no evidence as to whether restriction fragment length polymorphism of the renin gene is associated with any of the changes in the renin tissue level. For this reason we have determined renal renin activity in spontaneously hypertensive, Wistar-Kyoto and Brown Norway rats as well as in 22 recombinant inbred strains derived from F2 hybrids of spontaneously hypertensive and Brown Norway rats. 2. At the age of 4 months significantly lower renal renin activity was observed in spontaneously hypertensive rats than in both normotensive rat strains, Wistar-Kyoto and Brown Norway. The presence of the spontaneously hypertensive rat allele in recombinant inbred strains was associated with a substantially lower renal renin activity as compared with recombinant inbred strains bearing the Brown Norway rat allele. There was no relationship between renal renin activity and the polymorphism in either the angiotensinogen gene or the angiotensin-converting enzyme gene. 3. There was a borderline correlation between blood pressure and renal renin activity in recombinant inbred strains. Nevertheless, additional comparisons within recombinant inbred strains bearing the spontaneously hypertensive rat allele of the renin gene failed to reveal any significant relationship between blood pressure level and renal renin activity. 4. Our data suggest that the restriction fragment length polymorphism marking the renin gene of the spontaneously hypertensive rat is accompanied by an alteration in the renin-angiotensin system at the renal level. The mechanisms by which structural abnormalities of the renin gene might influence the renin level in the kidney remain to be investigated.

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