Effect of indomethacin on cerebrovascular reactivity in patients with type 2 diabetes mellitus

Aim: Impaired cerebral vasoreactivity to endothelium-dependent stimuli were described in type 2 diabetes mellitus (T2DM), but the mechanisms underlying that impairment are still unclear. The aim of this study was to investigate the role of cyclooxygenases' metabolites in response to acute hypercapnic stimulus in cerebral vessels, in patients with T2DM. Methods: Vascular responses in the breath-holding test (BHT) were assessed in the absence/presence of a non-selective, reversible-inhibitor of cyclooxygenases, indomethacin (INDO), by functional transcranial Doppler sonography of the middle cerebral artery (N of patients = 50; 33 men and 17 women). The functional hemodynamic parameter mean flow velocity (MFV) was assessed at rest, before and 90 min after 100 mg of INDO, and during the BHT. Breath holding index (BHI) [(MFV at the end of BHT minus MFV at rest)/MFV at rest) x 100/s of breath-holding] was calculated after BHT performed before and 90 min after INDO. Results: MFV at rest significantly decreased after INDO administration compared with a control condition before INDO (at rest before INDO from 49.36 +/- 15.09 to 36.72 +/- 8.45 after INDO, p < 0.001) However, overall cerebral vessel vasoreactivity to hypercapnia, evaluated with BHI, was significantly improved after INDO administration compared with the BHI before INDO administration (from 0.68 +/- 0.4 to 1.27 +/- 0.42, p < 0.001). Conclusions: The improvement in cerebral vasoreactivity in response to BHT after INDO administration suggests that the production of a vasoconstrictor metabolite of cyclooxygenase in diabetic patients was reduced by indomethacin consumption. (C) 2013 Elsevier Ireland Ltd. All rights reserved.