Predator Scent-Induced Sensitization of Hypertension and Anxiety-like Behaviors
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ORIGINAL RESEARCH
Predator Scent‑Induced Sensitization of Hypertension and Anxiety‑like Behaviors Baojian Xue1 · Jiarui Xue1 · Yang Yu4 · Shun‑Guang Wei4,5 · Terry G. Beltz1 · Robert B. Felder4,5 · Alan Kim Johnson1,2,3,5 Received: 13 July 2020 / Accepted: 11 November 2020 © Springer Science+Business Media, LLC, part of Springer Nature 2020
Abstract Post-traumatic stress disorder (PTSD), an anxiety-related syndrome, is associated with increased risk for cardiovascular diseases. The present study investigated whether predator scent (PS) stress, a model of PTSD, induces sensitization of hypertension and anxiety-like behaviors and underlying mechanisms related to renin–angiotensin systems (RAS) and inflammation. Coyote urine, as a PS stressor, was used to model PTSD. After PS exposures, separate cohorts of rats were studied for hypertensive response sensitization (HTRS), anxiety-like behaviors, and changes in plasma levels and mRNA expression of several components of the RAS and proinflammatory cytokines (PICs) in the lamina terminalis (LT), paraventricular nucleus (PVN), and amygdala (AMY). Rats exposed to PS as compared to control animals exhibited (1) a significantly greater hypertensive response (i.e., HTRS) when challenged with a slow-pressor dose of angiotensin (ANG) II, (2) significant decrease in locomotor activity and increase in time spent in the closed arms of a plus maze as well as general immobility (i.e., behavioral signs of increased anxiety), (3) upregulated plasma levels of ANG II and interleukin-6, and (4) increased expression of message for components of the RAS and PICs in key brain nuclei. All the PS-induced adverse effects were blocked by pretreatment with either an angiotensin-converting enzyme antagonist or a tumor necrosis factor-α inhibitor. The results suggest that PS, used as an experimental model of PTSD, sensitizes ANG II-induced hypertension and produces behavioral signs of anxiety, probably through upregulation of RAS components and inflammatory markers in plasma and brain areas associated with anxiety and blood pressure control. Keywords Predator scent stress · Behavior · Blood pressure · Renin–angiotensin system · Inflammation
Introduction Post-traumatic stress disorder (PTSD) is an anxiety-related syndrome triggered by stressful events (Nemeroff et al. 2006). There is significant comorbidity between PTSD and * Baojian Xue baojian‑[email protected] 1
Department of Psychological and Brain Sciences, University of Iowa, PBSB, 340 Iowa Ave, Iowa City, IA 52242, USA
2
Health and Human Physiology, University of Iowa, Iowa City, IA 52242, USA
3
Neuroscience and Pharmacology, University of Iowa, Iowa City, IA 52242, USA
4
Internal Medicine, University of Iowa, Iowa City, IA 52242, USA
5
The Franҫois M. Abboud Cardiovascular Research Center University of Iowa, Iowa City, IA 52242, USA
cardiovascular diseases. Most notably, there is a twofold increase in the prevalence of hypertension in PTSD patients in contrast to those without the psychological disorder (Cohen et al. 20
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