Abstract P389: Post-traumatic Stress-induced Sensitization of Angiotensin II Hypertension is Reversed by Blockade of Angiotensin-converting Enzyme or Tumor Necrosis Factor-alpha

Abstract

Using an Induction-Delay-Expression experimental paradigm, our previous studies demonstrated that post-traumatic stress disorder (PTSD) sensitizes angiotensin (ANG) II-elicited hypertension, which was associated with upregulation of central renin-angiotensin system (RAS) components and proinflammatory cytokines (PICs). The present study investigated whether inhibition of angiotensin-converting enzyme (ACE) or tumor necrosis factor-α (TNF-α) prior to PTSD blocks sensitization of ANG II-elicited hypertensive response. The resident-intruder paradigm was used to model PTSD. Each intruder rat (male Sprague-Dawley) was pretreated with ACE inhibitor (captopril, 0.5 mg/Ml) or with TNF-α inhibitor (pentoxifylline, PTX, 100 mg/kg/day) in the drinking water for two weeks and then exposed to a different resident (male Long-Evans) for 2 hours on three days with each session separated by 1 day. Beginning 3 days after the last exposure, the intruder (PTSD) rats and unstressed control rats received a subcutaneous infusion of ANG II (120 ng/kg/min) for 2 weeks. The PTSD rats had a significantly enhanced hypertensive response to the ANG II infusion and an upregulation of mRNA expression of RAS and PIC components and of a microglial marker in the lamina terminalis (LT) when compared to control rats. Both the sensitized hypertensive response and enhanced gene expression were blocked by pre-treatment with either ACE inhibitor or TNF-α antagonist. These results suggest that upregulation of the brain RAS and PICs produced by a severe stress contribute to PTSD-induced sensitization of the hypertensive response to ANG II.