Key result
Pretreatment with an ACE inhibitor (Δ21.3 mm Hg) or TNF-α inhibitor (Δ21.4 mm Hg) blocked the severe stress-induced sensitization of the hypertensive response to Ang II (Δ40.2 mm Hg) in rats.
Why the study?
PTSD is associated with increased cardiovascular disease risk, but whether Ang II-elicited hypertension is sensitized in PTSD models and blocked by ACE or TNF-alpha inhibition was unknown.
Does pretreatment with ACE or TNF-α inhibitors prevent stress-induced sensitization of Angiotensin II hypertension in a rat model of PTSD?
Does pretreatment with ACE or TNF-α inhibitors prevent stress-induced sensitization of Angiotensin II hypertension in a rat model of PTSD?
Absolute Event Rate: 21.3% vs 40.2%
Pretreatment with ACE or TNF-α inhibitors blocks the sensitization of Angiotensin II-induced hypertension caused by severe stress in a rat model of PTSD.
PTSD-linked sensitization of Ang II hypertension in rats warrants clinical caution; leaves open whether ACE or TNF-α inhibition prevents this in humans.
BACKGROUND: Post-traumatic stress disorder (PTSD) is characterized by a disordered stress response and associated with increased cardiovascular disease risk. The present study investigated whether angiotensin (Ang) II-elicited hypertensive response is sensitized in a model of PTSD and whether inhibition of angiotensin-converting enzyme (ACE) or tumor necrosis factor (TNF)-α prior to PTSD blocks this sensitization of Ang II hypertension. METHODS: The resident-intruder paradigm was used to model PTSD. Each intruder rat (male Sprague-Dawley) was given normal drinking water or was pretreated with either an ACE inhibitor (captopril) or a TNF-α inhibitor (pentoxifylline) in the drinking water for 2 weeks. Subsequently, they were exposed to a different resident (male Long-Evans) for 2 hours on 3 days with each session separated by 1 day and then received a subcutaneous infusion of Ang II for 2 weeks. RESULTS: The stressed rats had a significantly enhanced hypertensive response to the Ang II infusion (stressed Δ40.2 ± 3.9 mm Hg vs. unstressed Δ20.5 ± 4.5 mm Hg) and an upregulation of mRNA or protein expression of renin-angiotensin system (RAS) and proinflammatory cytokine (PIC) components and of a microglial marker in the lamina terminalis and hypothalamic paraventricular nucleus when compared with unstressed control rats. Both the sensitized hypertensive response and enhanced gene and protein expression were blocked by pretreatment with either ACE (Δ21.3 ± 3.9 mm Hg) or TNF-α inhibitor (Δ21.4 ± 2.6 mm Hg). CONCLUSIONS: The results indicate that upregulation of the brain RAS and PICs produced by severe stress contributes to traumatic-induced sensitization of hypertensive response to Ang II, and disorders such as PTSD may predispose individuals to development of hypertension.
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Xue et al. (2019) studied Post-traumatic stress disorder and Angiotensin II-induced hypertension. ACE inhibitor (captopril) or TNF-α inhibitor (pentoxifylline) vs. Normal drinking water (stressed and unstressed controls) was evaluated on Hypertensive response to Ang II infusion (change in blood pressure). Pretreatment with an ACE inhibitor (Δ21.3 mm Hg) or TNF-α inhibitor (Δ21.4 mm Hg) blocked the severe stress-induced sensitization of the hypertensive response to Ang II (Δ40.2 mm Hg) in rats.
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