Predator scent stress induces anxiety and sensitizes the angiotensin II‐elicited hypertensive response

Abstract

Post‐traumatic stress disorder (PTSD) is associated with increased risk of cardiovascular diseases. In the present study, we examined the cardiovascular, biochemical and behavioral consequences of exposing animals to a predatory scent paradigm. After exposures, we measured factors associated with stress responses in a standardized behavioral test. We also determined the hypertensive response to angiotensin (ANG) II and expression levels of the renin‐angiotensin system (RAS) and proinflammatory cytokines (PICs) in the lamina terminalis (LT), paraventricular nucleus (PVN) and amygdala (Amy). Rats (male Sprague‐Dawley) were placed in a plastic‐shoebox cage and exposed to coyote urine in three 20‐minute sessions on alternating days (stressed). A second group served as home‐cage controls. Three days after the last exposure, three separate cohorts of animals following an identical experimental protocol were studied for 1) sensitization of the hypertensive response, 2) performance in the elevated “plus” maze in order to assess anxiety and 3) changes in expression of mRNA for components of the RAS and markers of inflammation in the LT, PVN and Amy. Stressed rats, compared to the controls, had a significantly greater hypertensive response when challenged with a slow‐pressor dose of ANG II (sensitization), exhibited a significant preference to the closed arms as well as general immobility (i.e. enhanced anxiety) and an upregulated expression of several components of the RAS and PICs in the LT, PVN and amygdala. The results suggest that the predatory scent paradigm, a model for PTSD, sensitizes ANG II‐induced hypertension and induces behavioral signs of anxiety in rats, probably through upregulation of RAS and PICs components in key brain areas associated with fear and the central sympathetic control of blood pressure.Support or Funding InformationNIH HL139575