The Effects of Age and Cyclooxygenase Inhibition on the Cerebrovascular Response to a Metabolic Stimulus

Abstract

BackgroundProstaglandins, such as cyclooxygenase (COX), may play an important role in regulating the cerebral blood flow response to a stimulus. We have previously shown that the vasodilatory response to a chemical stimulus decreases with age, and this difference is abolished by COX inhibition. However, the effects of COX inhibition on the cerebrovascular response to an increase in metabolic demand during a cognitive challenge is unknown. This information is important due to the frequent use of COX inhibitors for pain management. Thus, the purpose of this study was to determine the effect of COX inhibition on the cerebrovascular response to a metabolic stimulus in young and older adults.MethodsSeventy‐six participants, including 42 young adults (YA; 26 ± 5 y) and 34 older adults (OA; 64 ± 6 y) completed the Stroop Color Word Test, which is a test of executive function. A subset of 42 participants (n = 22 YA, n = 20 OA) also completed the N‐back Test, which is a test of working memory. Beat‐to‐beat middle cerebral artery velocity (MCAv) and mean arterial pressure (MAP) were measured at baseline and in response to each cognitive test. Cerebrovascular conductance index (CVCi) was calculated as MCAv/MAP. The response to each cognitive test was calculated as the peak percent change (%Δ) from baseline. Oral administration of the COX inhibitor Indomethacin (Indo) was given at 1.2mg/kg. Cognitive tests were then repeated after a 120‐minute wash‐in period.ResultsAt baseline, YA had higher MCAv, CVCi, and lower MAP (p<0.01 for all) compared to OA. There were no significant differences between groups in the %Δ from baseline during the Stroop or N‐back test (p>0.05). During Indo, YA had higher MCAv (p<0.01), CVCi (p<0.01), and lower MAP (p<0.05) compared to OA. Indo decreased baseline MCAv and CVCi in both groups (p<0.01 for all) but had no effect on MAP (p>0.05). During Indo, the %Δ in MCAv during Stroop and N‐back was lower in YA (p<0.01) compared to baseline in YA. During Indo, the %Δ in MCAv was lower during Stroop in OA (p<0.01), with a trend for significance in OA during N‐back (p=0.06) compared to baseline. In YA during Indo, the %Δ in MAP was lower during Stroop (p<0.01) with a trend for significance during Nback (p=0.08) compared to baseline. In OA, the %Δ in MAP during N‐back was lower during Indo compared to baseline (p<0.05). Indo had no effect on the %Δ in CVCi (p>0.05). Importantly, there were group differences in the %Δ in MAP during Indo, such that the change was greater in OA compared with YA during Stroop (14.1 ± 1.3% vs. 10.6 ± 1.0%; p<0.05).ConclusionAfter administration of Indo, OA increased MAP to a greater extent during the Stroop test when compared to YA. These results suggest that OA required a larger increase in blood pressure to complete a test of executive function during COX inhibition. Because some COX inhibitors attenuate cerebral blood flow, OA may need to augment blood pressure to complete this metabolically‐challenging task.Support or Funding InformationThis research was funded by NIH grant HL118154.This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.