Hyper-reactivity of HPA axis in Fischer 344 rats is associated with impaired cardiovascular and behavioral adaptation to repeated restraint stress

Abstract

Fischer 344 (F344) rats are characterized by the hyper-reactive hypothalamic-pituitary-adrenal axis to stressful stimuli, while Lewis (LEW) rats are considered to be hypo-reactive. We studied stress-induced cardiovascular, neuroendocrine, and behavioral responses of adult male F344 and LEW rats subjected to the single (120 min) or the repeated restraint stress (daily 120 min for 1 week). Mean arterial pressure (MAP) and heart rate (HR) were measured in the restrained rats (n = 7–8 for each group) via a catheter inserted into the femoral artery. Baroreceptor sensitivity was evaluated using NO donor sodium nitroprusside and α₁-adrenoceptor agonist phenylephrine. The plasma levels of adrenocorticotropic hormone (ACTH), corticosterone, aldosterone, and adrenaline were determined before and during the restraint. Exploratory behavior was tested in open field test. F344 rats exerted the augmented stress-induced increase in plasma ACTH, corticosterone, and adrenaline as well as the impaired endocrine adaptation to the repeated stress compared to LEW rats. F344 rats exhibited higher MAP than LEW rats during single and repeated restraint. Moreover, repeatedly restrained F344 showed elevated HR and diminished baroreflex sensitivity. F344 and LEW rats exhibited similar total locomotor activity and the time spent in the center of open field arena, both parameters being decreased by the repeated restraint. The detailed analysis revealed altered pattern of locomotor behavior in F344 rats subjected to repeated restraint. In conclusion, F344 rats showed the impaired endocrine adaptation that resulted in allostatic overload, which might contribute to the impaired cardiovascular and behavioral adaptation to chronic stress observed in this strain.

Lay summary

• F344 rats, characterized by HPA axis hyper-reactivity, exhibited higher blood pressure during restraint than LEW rats. Moreover, repeatedly restrained F344 rats showed elevated heart rate and impaired baroreflex sensitivity. It can be concluded that a poor adaptation to the repeated stress in F344 rats is not only limited to the neuroendocrine response but also has important cardiovascular consequences.

Keywords:

• ACTH
• corticosterone
• adrenaline
• blood pressure
• baroreflex
• open field

Disclosure statement

No potential conflict of interest was reported by the authors.

Additional information

Funding

This work was supported by The Czech Science Foundation (GACR); under Grant 16-10349Y; and institutional support RVO:67985823.

Notes on contributors

Martin Vodička

Martin Vodicˇka designed the study, performed restraint stress and helped with open field test.

Anna Vavřínová

Anna Vavrˇínová designed the study, performed blood sampling and measurement of hormone levels and wrote the manuscript.

Anna Mikulecká

Martin Vodicˇka designed the study, performed restraint stress and helped with open field test.

Anna Mikulecká performed and analyzed open field test.

Josef Zicha

Martin Vodicˇka designed the study, performed restraint stress and helped with open field test.

Josef Zicha analyzed baroreflex measurement, helped with data interpretation and critical revision of manuscript.

Michal Behuliak

Martin Vodicˇka designed the study, performed restraint stress and helped with open field test.

Michal Behuliak performed blood pressure and baroreflex measurement, prepared figures, performed statistical analyses and wrote the manuscript.