Genetic Control of the Corticosterone Level at Rest and Under Emotional Stress in ISIAH Rats with Inherited Stress-Induced Arterial Hypertension

Redina, Olga E.; Smolenskaya, S. É.; Maslova, L. N.; Markel, A. L.

doi:10.3109/10641961003628502

Cited by 11 publications

(7 citation statements)

References 26 publications

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“…WBP11 was one of urinary polypeptides significantly down-regulated and specific for essential hypertension with left ventricular diastolic dysfunction that subsequently distinguished hypertensive patients with overt heart failure from healthy controls [ 29 ]. The QTL for kidney weight in the distal part of Chr.4 does not overlap with loci for blood pressure traits in ISIAH rats but overlaps with the locus where the ISIAH alleles significantly increase the basal level of corticosterone (Figure 3 ) [ 13 ]. Corticosterone may induce the formation of reactive oxygen species [ 30 ] and development of adaptive response to oxidative stress may influence the mRNA processing [ 31 ] causing both the induction of stress-response genes and inhibition of gene transcription [ 32 ].…”

Section: Resultsmentioning

confidence: 99%

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Candidate genes in quantitative trait loci associated with absolute and relative kidney weight in rats with Inherited Stress Induced Arterial Hypertension

et al. 2015

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BackgroundThe kidney mass is significantly increased in hypertensive ISIAH rats with Inherited Stress Induced Arterial Hypertension as compared with normotensive WAG rats. The QTL/microarray approach was carried out to determine the positional candidate genes in the QTL for absolute and relative kidney weight.ResultsSeveral known and predicted genes differentially expressed in ISIAH and WAG kidney were mapped to genetic loci associated with the absolute and relative kidney weight in 6-month old F2 hybrid (ISIAHxWAG) males. The knowledge-driven filtering of the list of candidates helped to suggest several positional candidate genes, which may be related to the structural and mass changes in hypertensive ISIAH kidney.In the current study, we showed that all loci found for absolute and relative kidney weight didn't overlap with significant or suggestive loci for arterial blood pressure level. So, the genes differentially expressed in ISIAH and WAG kidneys and located in these QTL regions associated with absolute and relative kidney weight shouldn't substantially influence the BP level in the 6 month-old ISIAH rats. However, in some cases, small effects may be suggested.ConclusionsThe further experimental validation of causative genes and detection of polymorphisms will provide opportunities to advance our understanding of the underlying nature of structural and mass changes in hypertensive ISIAH kidney.

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Section: Resultsmentioning

confidence: 99%

“…The details of QTL analysis were described earlier [ 8 , 13 ]. Genomic DNA was prepared from liver by the conventional method using Proteinase K and phenol-chloroform extraction.…”

Section: Methodsmentioning

confidence: 99%

Candidate genes in quantitative trait loci associated with absolute and relative kidney weight in rats with Inherited Stress Induced Arterial Hypertension

et al. 2015

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“…This allows us to assume that the sEH protein function in ISIAH rats is not changed, and the highly reliable increase in the transcription level of the Ephx2 gene in all analyzed tissues/organs of ISIAH rats may be related to the sequence features of the promoter region of this gene, or to the features of the signal regulation mechanisms of its expression. The second assumption can be based on the data we have on the localization of the Ephx2 gene in the genetic locus (QTL) on chromosome 15, which we previously associated with plasma corticosterone concentrations under the influence of emotional stress [61], as well as on data that the level of transcription of the Ephx2 gene significantly increases under the influence of emotional stress, which was shown when studying the level of its transcription in the renal medulla of ISIAH rats [62].…”

Section: Discussionmentioning

confidence: 99%

The differences in brain stem transcriptional profiling in hypertensive ISIAH and normotensive WAG rats

et al. 2019

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Background: The development of essential hypertension is associated with a wide range of mechanisms. The brain stem neurons are essential for the homeostatic regulation of arterial pressure as they control baroreflex and sympathetic nerve activity. The ISIAH (Inherited Stress Induced Arterial Hypertension) rats reproduce the human stress-sensitive hypertensive disease with predominant activation of the neuroendocrine hypothalamic-pituitaryadrenal and sympathetic adrenal axes. RNA-Seq analysis of the brain stems from the hypertensive ISIAH and normotensive control WAG (Wistar Albino Glaxo) rats was performed to identify the differentially expressed genes (DEGs) and the main central mechanisms (biological processes and metabolic pathways) contributing to the hypertensive state in the ISIAH rats. Results: The study revealed 224 DEGs. Their annotation in databases showed that 22 of them were associated with hypertension and blood pressure (BP) regulation, and 61 DEGs were associated with central nervous system diseases. In accordance with the functional annotation of DEGs, the key role of hormonal metabolic processes and, in particular, the enhanced biosynthesis of aldosterone in the brain stem of ISIAH rats was proposed. Multiple DEGs associated with several Gene Ontology (GO) terms essentially related to modulation of BP were identified. Abundant groups of DEGs were related to GO terms associated with responses to different stimuli including response to organic (hormonal) substance, to external stimulus, and to stress. Several DEGs making the most contribution to the inter-strain differences were detected including the Ephx2, which was earlier defined as a major candidate gene in the studies of transcriptional profiles in different tissues/organs (hypothalamus, adrenal gland and kidney) of ISIAH rats. Conclusions:The results of the study showed that inter-strain differences in ISIAH and WAG brain stem functioning might be a result of the imbalance in processes leading to the pathology development and those, exerting the compensatory effects. The data obtained in this study are useful for a better understanding of the genetic mechanisms underlying the complexity of the brain stem processes in ISIAH rats, which are a model of stresssensitive form of hypertension.

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“…QTL analysis is also an effective approach for determining common loci for several traits, where genes with pleiotropic effects on the traits under study can be located. Previously, using QTL analysis, we described the genetic loci associated with the level of blood pressure and the mass of the adrenal glands, kidneys, and heart [25,26], as well as the loci associated with the plasma corticosterone concentration in hypertensive ISIAH rats [27]. All the studied traits were associated with several loci suggesting polygenic control of the manifestation of the listed characters of ISIAH rats.…”

Section: Introductionmentioning

confidence: 98%

Hypothalamic Norepinephrine Concentration and Heart Mass in Hypertensive ISIAH Rats Are Associated with a Genetic Locus on Chromosome 18

Redina

Smolenskaya

Polityko

et al. 2021

JPM

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The relationship between activation of the sympathetic nervous system and cardiac hypertrophy has long been known. However, the molecular genetic basis of this association is poorly understood. Given the known role of hypothalamic norepinephrine in the activation of the sympathetic nervous system, the aim of the work was to carry out genetic mapping using Quantitative Trait Loci (QTL) analysis and determine the loci associated both with an increase in the concentration of norepinephrine in the hypothalamus and with an increase in heart mass in Inherited Stress-Induced Arterial Hypertension (ISIAH) rats simulating the stress-sensitive form of arterial hypertension. The work describes a genetic locus on chromosome 18, in which there are genes that control the development of cardiac hypertrophy associated with an increase in the concentration of norepinephrine in the hypothalamus, i.e., genes involved in enhanced sympathetic myocardial stimulation. No association of this locus with the blood pressure was found. Taking into consideration previously obtained results, it was concluded that the contribution to the development of heart hypertrophy in the ISIAH rats is controlled by different genetic loci, one of which is associated with the concentration of norepinephrine in the hypothalamus (on chromosome 18) and the other is associated with high blood pressure (on chromosome 1). Nucleotide substitutions that may be involved in the formation or absence of association with blood pressure in different rat strains are discussed.

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Genetic Control of the Corticosterone Level at Rest and Under Emotional Stress in ISIAH Rats with Inherited Stress-Induced Arterial Hypertension

Cited by 11 publications

References 26 publications

Candidate genes in quantitative trait loci associated with absolute and relative kidney weight in rats with Inherited Stress Induced Arterial Hypertension

Candidate genes in quantitative trait loci associated with absolute and relative kidney weight in rats with Inherited Stress Induced Arterial Hypertension

The differences in brain stem transcriptional profiling in hypertensive ISIAH and normotensive WAG rats

Hypothalamic Norepinephrine Concentration and Heart Mass in Hypertensive ISIAH Rats Are Associated with a Genetic Locus on Chromosome 18

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