Age-related autoregulatory dysfunction and cerebromicrovascular injury in mice with angiotensin II-induced hypertension

摘要: Hypertension in the elderly substantially contributes to cerebromicrovascular damage and promotes development of vascular cognitive impairment. Despite importance myogenic mechanism protection, it is not well understood how aging affects functional adaptation cerebral arteries high blood pressure. was induced young (3 months) aged (24 C57/BL6 mice by chronic infusion angiotensin II (AngII). In hypertensive mice, range flow autoregulation extended higher pressure values, pressure-induced tone middle artery (MCA) increased. markedly disrupted, MCAs did show adaptive increases tone. hypertension involved upregulation 20-HETE (20-hydroxy-5,8,11,14-eicosatetraenoic acid)/transient receptor potential cation channel, subfamily C (TRPC6) pathway this impaired mice. Downstream consequences cerebrovascular autoregulatory dysfunction AngII-induced included exacerbated disruption blood–brain barrier neuroinflammation (microglia activation proinflammatory cytokines chemokines), which were associated with hippocampal dependent function. Collectively, impairs protection brain hypertension, potentially exacerbating injury neuroinflammation.