Soluble epoxide hydrolase inhibition improves cognitive function and parenchymal artery dilation in a hypertensive model of chronic cerebral hypoperfusion.
Microcirculation
; 28(1): e12653, 2021 01.
Article
in En
| MEDLINE
| ID: mdl-32767848
ABSTRACT
OBJECTIVE:
Parenchymal arterioles (PAs) regulate perfusion of the cerebral microcirculation, and impaired PA endothelium-dependent dilation occurs in dementia models mimicking chronic cerebral hypoperfusion (CCH). Epoxyeicosatrienoic acids (EETs) are vasodilators; their actions are potentiated by soluble epoxide hydrolase (sEH) inhibition. We hypothesized that chronic sEH inhibition with trifluoromethoxyphenyl-3 (1-propionylpiperidin-4-yl) urea (TPPU) would prevent cognitive dysfunction and improve PA dilation in a hypertensive CCH model.METHODS:
Bilateral carotid artery stenosis (BCAS) was used to induce CCH in twenty-week-old male stroke-prone spontaneously hypertensive rats (SHSRP) that were treated with vehicle or TPPU for 8 weeks. Cognitive function was assessed by novel object recognition. PA dilation and structure were assessed by pressure myography, and mRNA expression in brain tissue was assessed by qRT-PCR.RESULTS:
TPPU did not enhance resting cerebral perfusion, but prevented CCH-induced memory deficits. TPPU improved PA endothelium-dependent dilation but reduced the sensitivity of PAs to a nitric oxide donor. TPPU treatment had no effect on PA structure or biomechanical properties. TPPU treatment increased brain mRNA expression of brain derived neurotrophic factor, doublecortin, tumor necrosis factor-alpha, sEH, and superoxide dismutase 3,CONCLUSIONS:
These data suggest that sEH inhibitors may be viable treatments for cognitive impairments associated with hypertension and CCH.
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Brain Ischemia
/
Cerebrovascular Circulation
/
Cognition
/
Epoxide Hydrolases
/
Hypertension
Type of study:
Prognostic_studies
Limits:
Animals
Language:
En
Journal:
Microcirculation
Journal subject:
ANGIOLOGIA
Year:
2021
Document type:
Article
Affiliation country:
Estados Unidos