Myocardial hypersensitivity to ischemic injury is not reversed by clonidine or propranolol in a predator-based rat model of posttraumatic stress disorder

•Individuals with posttraumatic stress disorder (PTSD) are at increased risk for cardiovascular disease. We previously reported that a predator-based model of PTSD increases myocardial sensitivity to ischemic injury. Heightened sympathetic signaling has a well-established role in the formation of anxiety associated with PTSD and may also contribute to worsening of myocardial injury in the ischemic heart. Thus, we examined whether suppression of sympathetic tone protects the ischemic heart in rats subjected to this model of PTSD. Rats were treated with saline or clonidine throughout the 31-day stress paradigm. Behavior on the elevated plus maze (EPM) was assessed on Day 32, and hearts were subjected to an ischemic insult on day 33. Stressed rats exhibited increased anxiety on the EPM and significantly larger myocardial infarcts following ischemia. Clonidine reversed the anxiety-like behavior but had no impact on infarct size. In a subsequent experiment, rats were treated with propranolol in their drinking water throughout the stress paradigm. Propranolol had no effect on either anxiety or myocardial sensitivity to ischemic injury. These findings suggest that the myocardial hypersensitivity to ischemic injury observed in this model is not caused by increased sympathetic tone or chronic β-adrenergic receptor signaling. •The psychosocial stress model of PTSD causes myocardial hypersensitivity to ischemic injury.•Clonidine blocks anxiety-like behavior but not myocardial hypersensitivity to ischemia.•Propranolol does not block anxiety or hypersensitivity to ischemia in this animal model of PTSD.