Stress and hypertensive disease: adrenals as a link. Experimental study on hypertensive ISIAH rat strain

Antonov, Y.; Alexandrovich, Yuriy V; Redina, Olga E.; Gilinsky, M. A.; Markel, A. L.

doi:10.3109/10641963.2015.1116546

Cited by 14 publications

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“…Our previous studies confirmed the reduced activity of 11β-hydroxysteroid dehydrogenase type 2 (11β-HSD2) in adrenal glands of ISIAH rats [21] and in peripheral blood plasma [10]. It was shown that the loss-of-function mutations or inhibition of 11β-HSD2 results in overstimulation of the mineralocorticoid receptor by glucocorticoids and causes salt-sensitive hypertension [22].…”

Section: Discussionsupporting

confidence: 74%

“…The peripheral plasma aldosterone concentration and secretion rates of corticosterone, 11-dehydrocorticosterone and deoxycorticosterone measured by the adrenal vein cannulation were significantly higher in the ISIAH rats as compared to control WAG rats [10]. The sympathetic adrenal medullary function assessed by measurement of the adrenal catecholamine content showed decreased concentrations of dopamine and norepinephrine, but significantly enhanced level of epinephrine in the adrenals of ISIAH rats [9].…”

Section: Introductionmentioning

confidence: 99%

“…The sympathetic adrenal medullary function assessed by measurement of the adrenal catecholamine content showed decreased concentrations of dopamine and norepinephrine, but significantly enhanced level of epinephrine in the adrenals of ISIAH rats [9]. It was suggested that the genetically determined enhanced stress responsiveness and hypertension development in ISIAH rats may be a result of the specificity of its adrenal gland function [10]. …”

Section: Introductionmentioning

confidence: 99%

“…The differences in the transcription activity of several genes measured in the adrenal glands of hypertensive ISIAH and control WAG rats [9, 10] demonstrated that the selection of the ISIAH rat strain for the enhanced responsiveness to mild emotional stress could lead to accumulation of the genetic changes which may affect the hypertension development.…”

Section: Introductionmentioning

confidence: 99%

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Molecular determinants of the adrenal gland functioning related to stress-sensitive hypertension in ISIAH rats

et al. 2016

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BackgroundThe adrenals are known as an important link in pathogenesis of arterial hypertensive disease. The study was directed to the adrenal transcriptome analysis in ISIAH rats with stress-sensitive arterial hypertension and predominant involvement in pathogenesis of the hypothalamic-pituitary-adrenal and sympathoadrenal systems.ResultsThe RNA-Seq approach was used to perform the comparative adrenal transcriptome profiling in hypertensive ISIAH and normotensive WAG rats. Multiple differentially expressed genes (DEGs) related to different biological processes and metabolic pathways were detected.The discussion of the results helped to prioritize the several DEGs as the promising candidates for further studies of the genetic background underlying the stress-sensitive hypertension development in the ISIAH rats. Two of these were transcription factor genes (Nr4a3 and Ppard), which may be related to the predominant activation of the sympathetic-adrenal medullary axis in ISIAH rats. The other genes are known as associated with hypertension and were defined in the current study as DEGs making the most significant contribution to the inter-strain differences. Four of them (Avpr1a, Hsd11b2, Agt, Ephx2) may provoke the hypertension development, and Mpo may contribute to insulin resistance and inflammation in the ISIAH rats.ConclusionsThe study strongly highlighted the complex nature of the pathogenesis of stress-sensitive hypertension. The data obtained may be useful for identifying the common molecular determinants in different animal models of arterial hypertension, which may be potentially used as therapeutic targets for pharmacological intervention.Electronic supplementary materialThe online version of this article (doi:10.1186/s12864-016-3354-2) contains supplementary material, which is available to authorized users.

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Section: Discussionsupporting

confidence: 74%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Molecular determinants of the adrenal gland functioning related to stress-sensitive hypertension in ISIAH rats

et al. 2016

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“…Furthermore, the reduction in glomerular number is also associated with hypertension representing a vicious cycle where both the loss of glomeruli induces hypertension and hypertension promotes glomerular loss [11,24,25]. On the other hand, under stressful conditions, the hypothalamicpituitary-adrenal axis is further activated; recently, it has been demonstrated that a dominance of this axis over the renin-angiotensin-aldosterone system induce hypertension [26,27]. This reinforces the importance of reducing stress during any phase of life.…”

Section: Discussionmentioning

confidence: 86%

Immediate and Late Effects of Stress on Kidneys of Prepubertal and Adult Rats

Marchon

Ribeiro

Costa

et al. 2018

Kidney Blood Press Res

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Background/Aims: Stress had been related to physiological and morphological alterations in different organs, however kidney morphology and function after stress conditions are not well-known. To evaluate the effects of chronic stress on renal morphology in prepubertal and adult rats, and to investigate if the effects of induced stress remain stable or worsen following removal of the stress stimuli. Methods: Forty prepubertal rats (4 weeks old) and thirty six adult rats (10 weeks old) were used. Each age group was divided a into control group and a stressed group. Stressed animals were restrained in rigid tubes 2 hours per day for 6 weeks. Animals were euthanized 24 hours after the last stress stimulus for immediate evaluation (50% of the groups), and 6 weeks after the last stress stimulus for late evaluation (50% of the groups). Kidney weight and volume, cortical-medullar ratio, glomerular volumetric density, volume-weighted glomerular volume, and number of glomeruli per kidney were evaluated using the Image J software. Results: Prepubertal stressed animals showed reduced kidney weight and volume, and increased cortical-medullar ratio in comparison to its control group when evaluated immediately. Furthermore, stressed prepubertal and adult animals evaluated immediately had reduced glomerular volumetric density. Most importantly, all stressed groups exhibited reduced number of glomeruli per kidney. Other analyzed parameters did not difeer significantly the groups. Conclusion: Chronic stress induced before and after puberty led to irreversible glomerular loss, however, renal impairment was interrupted by removal of the stress stimuli.

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Stress, Genes, and Hypertension. Contribution of the ISIAH Rat Strain Study

Redina

Markel

2018

Curr Hypertens Rep

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Recent findings helped to characterize the main neuroendocrine mechanisms and the specificity of the genetic background contributing to the stress-sensitive hypertension development in the ISIAH rats. The ISIAH rat strain, which is an original model of the stress-sensitive arterial hypertension, can be considered as "living" proof that the genetic predisposition to increased stress-reactivity can lead to the development of persistent stress-dependent arterial hypertension. The ISIAH rat strain is characterized by the genetically determined enhanced response of the neuroendocrine and renal regulatory systems to stress and is a suitable model that allows one to explore the genetic and physiological mechanisms involved in stress-sensitive hypertension development. There are common genetic loci (QTLs) associated with both basal and stress-induced blood pressure (BP) levels as well as QTLs associated with BP and other traits, which may be related to hypertension development in ISIAH rats. Multiple genes differentially expressed in the target organs/tissues of hypertensive ISIAH and normotensive control rats are associated with many biological processes and metabolic pathways involved in stress response and arterial hypertension. The genotype of ISIAH rats is characterized by numerous specific and common SNPs as compared with other models of hypertensive rats. The results of the studies are valuable for the search for genetic markers specific for stress-induced arterial hypertension, as well as for the selection of new molecular targets that may be potentially useful for prevention and/or therapy of hypertensive disease.

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Stress and hypertensive disease: adrenals as a link. Experimental study on hypertensive ISIAH rat strain

Abstract: ISIAH rats may serve as a living proof that stress may produce sustained hypertension, and genetically determined enhanced stress responsiveness of corticosterone and, especially, aldosterone may play a crucial role in the mechanism of hypertension development.

Cited by 14 publications

References 49 publications

Molecular determinants of the adrenal gland functioning related to stress-sensitive hypertension in ISIAH rats

Molecular determinants of the adrenal gland functioning related to stress-sensitive hypertension in ISIAH rats

Immediate and Late Effects of Stress on Kidneys of Prepubertal and Adult Rats

Stress, Genes, and Hypertension. Contribution of the ISIAH Rat Strain Study

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