The Impact of Age and Sex on Cerebral and Large Artery Stiffness and the Response to Pulse Pressure

Vascular aging is characterized by a tandem increase in pulse pressure and large elastic artery stiffness. Greater stiffness of the large arteries leads to elevated pulse pressure transmitted into the cerebral circulation, causing dysfunction. However, little is known in females about age-related stiffening of the arteries and the impacts of high pulse pressure on the cerebral vasculature. To examine the effects of sex and age on the cerebral artery response to pulse pressure, we studied cerebral arteries collected from young and old female and male C57BL/6 mice. Isolated cerebral arteries were exposed ex vivo to static pressure, low pulse pressure, and high pulse pressure. Exposure to high pulse pressure impaired endothelium-dependent dilation in cerebral arteries from young female and male mice, with impairments also occurring in young female cerebral arteries after exposure to low pulse pressure. In contrast, exposure to low or high pulse pressure did not impact cerebral artery endothelium-dependent dilation for old male or female mice. During exposure to high pulse pressure, young females had higher cerebral artery compliance compared with young males and old females. Old mice also had higher cerebral artery passive stiffness and aortic pulse wave velocity compared with young mice. We also found age and sex differences in arterial wall thickness, collagen and elastin content, and matrix metalloproteinase 9 expression. Taken together, young female mice have more compliant cerebral arteries, which are more susceptible to endothelial dysfunction caused by pulse pressure.