Arterial stiffness is associated with overall and cardiovascular-specific mortality, and this association is exacerbated in women over 55 yr of age. Recent literature supports that stimulation of the angiotensin II type 2 receptor (AT2R) can protect from arterial stiffening, and that AT2R has a greater role in female cardiovascular physiology relative to males. The current study aimed to investigate the role of the AT2R in sex differences in aging-associated arterial stiffness. In female mice, the aging-related increase in arterial stiffness is temporally associated with a loss of aortic AT2R mRNA expression, but this is not observed in males. Chronic AT2R inhibition in vivo increases arterial stiffening in young female and male mice, as well as middle-aged female mice. The inhibition of AT2R is associated with an increase in aortic integrinα5 mRNA expression in young males and an increase in collagen1α1 mRNA expression in middle-aged females. Overall, these findings identify a sex-specific mechanism of aging-associated arterial stiffening in mice involving AT2R attenuation and collagen upregulation in females.NEW & NOTEWORTHY This is the first investigation to show that the angiotensin II type 2 receptor (AT2R) attenuates aging-associated arterial stiffness in middle-aged female mice. The AT2R also attenuates arterial stiffness in young female and male mice, but there are sex-specific molecular mechanisms that contribute to the role of AT2R in vessel stiffening.
Keywords: aging; angiotensin II type 2 receptor; arterial stiffness; sex differences.