Sex Differences in the Cerebrovascular Response to a Metabolic Stimulus

Abstract

BackgroundBlood pressure control and regulation of cerebral blood flow are influenced by biological sex. We have previously demonstrated sex differences in cerebrovascular reactivity to hypercapnia in young adults. However, sex differences in the cerebrovascular response to a metabolic stimulus are unknown. As prostaglandins play a role in regulating cerebrovascular reactivity, evaluating cerebrovascular responses to a metabolic stimulus with cyclooxygenase (COX) inhibition may reveal important differences between males and females. Therefore, the purpose of this study was to investigate sex differences in the cerebrovascular response to a metabolic stimulus with and without COX inhibition in young adults.MethodsForty‐three young adults, 21 males (age = 28 ± 5 y) and 22 females (age = 25 ± 5 y), completed two levels of difficulty of the Stroop Color Word Test and the average response was calculated. Beat‐to‐beat mean arterial pressure (MAP) and middle cerebral artery velocity (MCAv) were measured at baseline and in response to each level of the Stroop test before and after administration of the COX inhibitor indomethacin. The peak MAP, MCAv, pulse pressure (PP), and cerebral pulsatility index (PI) responses were calculated as the highest 3‐beat average during each Stroop test.ResultsAt rest, MCAv was higher (Females: 65 ± 2, Males: 55 ± 2 cm/s, p < 0.01) and PI was lower (Females: 0.70 ± 0.02, Males: 0.78 ± 0.02, p < 0.05) in females compared to males, with no differences in MAP or PP. There were no differences in the percent change or peak MCAv, MAP, PP, or PI between males and females in response to the metabolic stimulus. COX inhibition reduced MCAv (Females: −28 ± 2%, Males: −28 ± 3%, p < 0.01 compared to baseline) and increased PI (Females: 17 ± 2%, Males: 20 ± 4%, p < 0.01 compared to baseline), with no change in MAP or PP. During COX inhibition, MCAv at rest was higher (Females: 46 ± 2, Males: 38 ± 1 cm/s, p < 0.01) and PI was lower (Females: 0.81 ± 0.03, Males: 0.93 ± 0.03, p < 0.05) in females compared to males, with no differences in MAP or PP. During COX inhibition, the percent change in MCAv, MAP, and PI in response to the metabolic stimulus did not differ between groups (p > 0.05); however, the percent change in PP during the metabolic stimulus was greater in males compared to females (Males: 16 ± 2%, Females: 9 ± 1%, p < 0.01).ConclusionYoung females had greater MCAv and lower PI at rest and this difference persisted following COX inhibition. Prior to COX inhibition, there were no differences between males and females in response to the metabolic stimulus. After COX inhibition, young males demonstrated a greater change in PP in response to the metabolic stimulus. These results suggest that COX inhibition reveals sex differences in the PP response to a metabolic stimulus.Support or Funding InformationFundingThis research was funded by NIH grant HL118154.