Alterations of Neurohumoral Response to Acute Stress in Spontaneously Hypertensive Rats Subjected to Long-Term Isolation

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Hypertension is a serious disease characterized by a sustained or recurrent increase in blood pressure, which can lead to various complications. Here, we studied the effect of genetically determined arterial hypertension in rats on their adaptation to long-term isolation and subsequent response to acute restraint stress. Male SHR rats with spontaneous hypertension were maintained in individual cages for 14 weeks. The serum levels of corticosterone, glucose, and pro- and anti-inflammatory cytokines and salivary α-amylase activity were studied, and the expression of genes associated with the regulation of steroidogenesis in the adrenal glands was evaluated. There were no significant changes in the parameters of the hypothalamic-pituitary-adrenocortical and sympatho-adrenal systems after isolation. Nevertheless, the preliminary isolation significantly affected the response to moderate restraint stress, including the expression of the regulatory genes Fkbp5 and Star in the adrenal glands and the content of proinflammatory cytokines IL-1β and IL-6 in the blood, although the changes in these indices were relatively subtle. This may reflect the predisposition of animals in isolation to develop quite specific stress-related changes.

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Sobre autores

L. Tretyakova

Institute of Higher Nervous Activity and Neurophysiology of the RAS

Email: m_stepanichev@ihna.ru
Rússia, Moscow

A. Kvichansky

Institute of Higher Nervous Activity and Neurophysiology of the RAS

Email: m_stepanichev@ihna.ru
Rússia, Moscow

Yu. Moiseeva

Institute of Higher Nervous Activity and Neurophysiology of the RAS

Email: m_stepanichev@ihna.ru
Rússia, Moscow

V. Ovchinnikova

Institute of Higher Nervous Activity and Neurophysiology of the RAS

Email: m_stepanichev@ihna.ru
Rússia, Moscow

D. Mamedova

Institute of Higher Nervous Activity and Neurophysiology of the RAS

Email: m_stepanichev@ihna.ru
Rússia, Moscow

O. Nedogreeva

Institute of Higher Nervous Activity and Neurophysiology of the RAS

Email: m_stepanichev@ihna.ru
Rússia, Moscow

N. Lazareva

Institute of Higher Nervous Activity and Neurophysiology of the RAS

Email: m_stepanichev@ihna.ru
Rússia, Moscow

M. Onufriev

Institute of Higher Nervous Activity and Neurophysiology of the RAS

Email: m_stepanichev@ihna.ru
Rússia, Moscow

N. Gulyaeva

Institute of Higher Nervous Activity and Neurophysiology of the RAS

Email: m_stepanichev@ihna.ru
Rússia, Moscow

M. Stepanichev

Institute of Higher Nervous Activity and Neurophysiology of the RAS

Autor responsável pela correspondência
Email: m_stepanichev@ihna.ru
Rússia, Moscow

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2. Fig. 1. Effect of social isolation on biochemical indices of stress-responsiveness in blood and saliva: (a) and (b) - changes in blood glucose and CORT in SHR rats during 60 min of acute moderate immobilisation stress, (c) - α-amylase activity in saliva from SHR rats before and after 60 min of acute moderate immobilisation stress. Data are presented as boxes (Me [Q1-Q3]) with whiskers (range min - max). * - p < 0.05, ** - p < 0.01, *** - p < 0.001 and **** - p < 0.0001 by Dunnett's criterion for multiple comparisons.

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3. Fig. 2. Effect of acute moderate immobilisation stress on the content of pro-inflammatory and anti-inflammatory cytokines and C-reactive protein in the blood of rats of SOC and WPI groups. "Control" - rats not exposed to acute stressor. Data are presented as boxes (Me [Q1-Q3]) with whiskers (min-max spread). * - p < 0.012 and ** - p < 0.01 by Mann-Whitney test for independent variables.

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4. Fig. 3. Effect of acute moderate immobilisation stress on relative adrenal mass (a) and mRNA transcript content of genes encoding the adrenocorticotropin receptor Mc2r (b) and glucocorticoid receptor Nr3c1 (c), associated with synthesis and metabolism of corticosteroids Hsd11b1 (d), Cyp11a1 (e), Cyp11b1 (f), transcription factor Fkbp5 (g) and steroid hormone synthesis regulatory protein Star (h) in adrenal glands of rats of SOC and IZO groups. ‘Control’ - rats not exposed to acute stressor. Data are presented as boxes (Me [Q1-Q3]) with whiskers (min-max difference). * - p < 0.012 and ** - p < 0.01 by Mann-Whitney test for independent variables.

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