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 about age-related stiffening of the arteries and the impacts of high pulse pressure on the cerebral vasculature in females. 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 posterior cerebral arteries (141.3 ± 3.9 μm diameter) were exposed ex vivo to acute 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 had minimal effects on cerebral artery endothelium-dependent dilation in old male and female mice. During exposure to high pulse pressure, young females had higher cerebral artery compliance compared with young males and old females. Old mice 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.<b>NEW & NOTEWORTHY</b> Age-related increases in arterial stiffness and pulse pressure are associated with cerebrovascular dysfunction; yet sex differences in these factors remain unclear. We found that cerebral artery passive stiffness was greater with age, independent of sex. With exposure to acute pulse pressure, young, compliant female cerebral arteries had a more pronounced decline in endothelial function. Thus, females may be more susceptible to cerebrovascular dysfunction due to age-related increases in pulse pressure.