Uncoupling of Ca²⁺ sparks from BK channels in cerebral arteries underlies hypoperfusion in hypertension-induced vascular dementia.

ABSTRACT: The deficit in cerebral blood flow (CBF) seen in patients with hypertension-induced vascular dementia is increasingly viewed as a therapeutic target for disease-modifying therapy. Progress is limited, however, due to uncertainty surrounding the mechanisms through which elevated blood pressure reduces CBF. To investigate this, we used the BPH/2 mouse, a polygenic model of hypertension. At 8 mo of age, hypertensive mice exhibited reduced CBF and cognitive impairment, mimicking the human presentation of vascular dementia. Small cerebral resistance arteries that run across the surface of the brain (pial arteries) showed enhanced pressure-induced constriction due to diminished activity of large-conductance Ca²⁺-activated K⁺ (BK) channels-key vasodilatory ion channels of ce

SUBMITTER: Taylor JL 

PROVIDER: S-EPMC10433456 | biostudies-literature | 2023 Aug

REPOSITORIES: biostudies-literature