Stress-induced Per1 expression in the brain is altered in hypertensive rats

Abstract

Hypertension (HTN) is an increasingly prevalent cardiovascular disorder that influences patients’ lives and adds a significant burden to the healthcare system. Stress may contribute to the development of HTN through various mechanisms, including repeated blood pressure elevations and the secretion of vasoconstricting hormones. Individuals with HTN, conversely, may have altered responses to stress. The goal of this study was to determine how neurological responses to control, acute stress and repeated stress conditions are affected by pre-existing HTN. We evaluated the activation of brain regions involved in neuroendocrine and cardiovascular control (i.e., the paraventricular [PVN] and dorsomedial [DMH] hypothalamic nuclei) by quantifying neurons expressing period-1 (Per1) and Fos in these regions. We hypothesized that pre-existing HTN would reduce the basal number of activated PVN and DMH neurons under non-stressed control conditions, but would enhance the activational response to acute emotional stress. We further hypothesized that animals with HTN would demonstrate exaggerated responses to repeated stress exposure. Adult male rats of the normotensive Wistar-Kyoto (WKY) and spontaneously hypertensive (SHR) strains were exposed to acute (30min x 1d) or repeated (30min x 14d) restraint stress near the beginning (0900h) of their light cycle. Rats were perfused with paraformaldehyde and coronal brain sections (30μm) collected and immunohistochemically stained for Per1 and Fos. Stained cells were quantified by ImageJ analysis of digitally-captured photomicrographs. Cell counts were taken from 5 or 4 sections throughout the rostrocaudal extent of the PVN or DMH, respectively, and compared by t-test with significance determined at p≤0.05. Acute restraint stress significantly increased the number of Fos-expressing neurons, compared to control levels, in the PVN and DMH of both WKY and SHR animals. In both strains, repeated exposure to restraint led to a habituated Fos response. Per1 expression showed a similar pattern in the SHR PVN, but neither acute nor repeated stress altered Per1 expression in the PVN of WKY rats. Interestingly, Per1 expression in the DMH varied by strain and treatment group. Control levels of Per1 in SHR were significantly reduced compared to WKY. Acute restraint reduced the number of Per1-positive neurons in WKY but not in SHR. Following repeated restraint, the number of Per1-expressing neurons was restored to control levels in WKY but was elevated in SHR to a level significantly greater than control. Our data indicate that pre-existing HTN impacts how stress is processed in the brain. More specifically, while chronic or repeated stress is known to have negative health consequences, our findings suggest that acute stress may be of greater concern to hypertensive individuals. This project was supported in part by NIH Grant 5G12RR008124. This is the full abstract presented at the American Physiology Summit 2023 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.