Association between platelet inhibition in the blood and cerebrovascular function in healthy young and older adults

Abstract

Platelet activation may contribute to age-related cerebrovascular dysfunction by interacting with the endothelial cells that regulate the response to vasodilatory stimuli. The purpose of this study was to evaluate the relationship between a platelet inhibitor, prostacyclin, and cerebrovascular function in healthy young and older adults before and after cyclooxygenase inhibition. We hypothesized that higher levels of prostacyclin would be positively associated with cerebrovascular function. Healthy young (n=36; 25 ± 4 yrs; 19 women, 17 men) and older (n=12; 62 ± 2 yrs; 8 women, 4 men) adults who were not taking daily aspirin participated in the study. Prostacyclin was determined by levels of 6-keto-PGF1α in the blood. On a separate study visit, cerebrovascular function was assessed by cerebrovascular reactivity (CVR) to hypercapnia in the middle cerebral artery before (CON) and 90 minutes after cyclooxygenase inhibition with indomethacin (INDO) at 1.2 mg/kg. Participants were instrumented with a transcranial Doppler ultrasound which continuously recorded middle cerebral artery velocity, a nasal cannula to measure end-tidal CO2, a finger blood pressure cuff to measure beat-by-beat blood pressure, and a mask with a one-way valve to prevent rebreathing. CVR was calculated as the slope of the relationship between middle cerebral artery velocity and the change in end-tidal CO2 during stepwise elevations in CO2. The associations between prostacyclin and CVR were analyzed using Pearson's Product-Moment correlations. In young adults, there were no associations between prostacyclin and CVR during CON (r = 0.11, p = 0.54) or INDO (r = 0.15, p = 0.39). In older adults, there was a trend for an association between prostacyclin and CVR during CON (r = 0.52, p = 0.08), but no association during INDO (r = -0.41, p = 0.18). We also evaluated the relationship between prostacyclin and the change in CVR between conditions. We found no association in young adults (r = 0.15, p = 0.37); however, in older adults, those with higher baseline prostacyclin levels demonstrated a greater change in CVR (r = 0.69, p = 0.01). In conclusion, there was a trend for a positive association between platelet inhibition and cerebrovascular function in older adults. Furthermore, older adults may rely more on cyclooxygenase products to mediate CVR. Future studies could evaluate how platelet activation may contribute to age-related changes in cerebrovascular function.