Epidemiological studies demonstrate that in addition to the increased prevalence of
hypertension in old patients, the deleterious cerebrovascular effects of hypertension
( including atherosclerosis, stroke, and vascular cognitive impairment) are also exacerbated
in elderly individuals. The cellular mechanisms by which aging and hypertension interact
to promote cerebrovascular pathologies are not well understood. To test the hypothesis
that aging exacerbates high pressure-induced mitochondrial oxidative stress, we exposed
isolated segments of the middle cerebral arteries of young ( 3 months) and aged (
24 months) C57BL/6 mice to 60 or 140 mmHg intraluminal pressure and assessed changes
in mitochondrial reactive oxygen species production using a mitochondria-targeted
redox-sensitive fluorescent indicator dye ( MitoSox) by confocal microscopy. Perinuclear
MitoSox fluorescence was significantly stronger in high pressure-exposed middle cerebral
arteries compared with middle cerebral arteries of the same animals exposed to 60
mmHg, indicating that high pressure increases mitochondrial reactive oxygen species
production in the smooth muscle cells of cerebral arteries. Comparison of young and
aged middle cerebral arteries showed that aging exacerbates high pressure-induced
mitochondrial reactive oxygen species production in cerebral arteries. We propose
that increased mechanosensitive mitochondrial oxidative stress may potentially exacerbate
cerebrovascular injury and vascular inflammation in aging.
