Abstract Body: Introduction: Patients with post-traumatic stress disorder (PTSD), a disorder of extreme stress, have higher heart rates and blood pressures as well as an increased prevalence of resistant hypertension. Chronic psychological stress has been associated with increased risk for developing cardiovascular disease and hypertension, however the exact mechanism linking the two is unknown.

Methods: Two mouse models were utilized, PTSD-like mice (control: non-traumatized mice) and mice with generalized anxiety (BPH/2J, control: BPN/3J). Mice underwent noninvasive blood pressure measurement. Thoracic aortae were assessed for changes in compliance by parallel-wire myography and alterations in aortic wall structure via histology. Thoracic aortic aneurysms were induced through periadventitial application of a 0.5M CaCl₂ solution to the descending thoracic aorta. Thoracic aortic diameter was measured 4-weeks post-surgery by digital microscopy. Allopregnanolone, a novel therapeutic, was administered to BPH/2J mice (5mg/kg/day) via osmotic pump for 6-weeks starting 2-weeks prior to thoracic aortic aneurysm surgery. Thoracic aortic diameter was measured 4-weeks post-surgery.

Results: PTSD and BPH/2J mice had significantly increased systolic blood pressures. Total medial collagen was elevated in the descending thoracic aorta of PTSD and BPH/2J mice that correlated with a decrease in thoracic aortic compliance. PTSD and BPH/2J mice had significantly larger thoracic aortic aneurysms 4-weeks post-surgery. Allopregnanolone suppressed thoracic aortic aneurysm acceleration in BPH/2J mice.

Conclusion: Stressed-induced hypertension can trigger extracellular matrix remodeling resulting in compensatory stiffening of the thoracic aorta. In the presence of aortopathy, neurogenic hypertension can accelerate disease progression which may be suppressed by allopregnanolone.