Carbon dioxide mediated vasomotion of extra-cranial cerebral arteries in humans: A role for prostaglandins?

Abstract

Extra-cranial cerebral blood vessels are implicated in the regulation of cerebral blood flow during changes in arterial CO₂; however, the mechanisms governing CO₂ mediated vasomotion of these vessels in humans remain unclear. We determined if cyclooxygenase inhibition with Indomethacin (INDO) reduces the vasomotor response of the internal carotid artery (ICA) to changes in end-tidal CO₂ (P_ETCO₂). Using a randomized single-blinded placebo controlled study, participants (n = 10) were tested on two occasions, before and 90-minutes following oral INDO (1.2mg/kg) or placebo. Concurrent measurements of beat-by-beat velocity, diameter, and blood flow of the ICA were made at rest and during steady-state stages (4-min) of iso-oxic hypercapnia (+3, +6, +9mmHg P_ETCO₂) and hypocapnia (−3, −6, −9mmHg P_ETCO₂). To examine if INDO affects ICA vasomotion independent of cyclooxygenase inhibition, two participant subsets (each n = 5) were tested before and following oral Ketorolac (post 45-min, 0.25mg/kg) or Naproxen (post 90-min, 4.2mg/kg). During pre-drug testing in the INDO trial, the ICA dilated during hypercapnia at +6mmHg (4.72 ± 0.45mm vs. 4.95 ± 0.51mm; P<0.001) and +9mmHg (4.72 ± 0.45mm vs. 5.12 ± 0.47mm; P<0.001), and constricted during hypocapnia at −6mmHg (4.95 ± 0.33mm vs. 4.88 ± 0.27mm; P<0.05) and −9mmHg (4.95 ± 0.33mm vs. 4.82 ± 0.27mm; P<0.001). Following INDO, vasomotor responsiveness of the ICA to hypercapnia was reduced by 67 ± 28% (0.045 ± 0.015 vs. 0.015 ± 0.012mm ⋅ mmHg P_ETCO₂⁻¹). There was no effect of the drug in the Ketorolac and Naproxen trials. We conclude that: 1) INDO markedly reduces the vasomotor response of the ICA to changes in P_ETCO₂; and 2) INDO may be reducing CO₂ mediated vasomotion via a mechanism(s) independent of cyclooxygenase inhibition.

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