title: Effect of indomethacin on cerebrovascular reactivity in patients with type 2 diabetes mellitus.
abstract: OBJECTIVE
  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 90min after 100mg of INDO, and during the BHT. Breath holding index (BHI) [(MFV at the end of BHT minus MFV at rest)/MFV at rest)×100/s of breath-holding] was calculated after BHT performed before and 90min 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.
authors.affiliation: Department of Neurology, Dubrava University Hospital, Zagreb, Croatia. Electronic address: vvuletic@kbd.hr.
authors.forename: Vladimira
authors.initials: V
authors.lastname: Vuletic
authors.affiliation: Department of Physiology and Immunology, Faculty of Medicine Osijek, University Josip, Juraj Strossmayer, Osijek, Croatia.
authors.forename: Ines
authors.initials: I
authors.lastname: Drenjancevic
authors.affiliation: Department of Endocrinology, Diabetes and Metabolic Disorders, Dubrava University Hospital, Zagreb, Croatia.
authors.forename: Dario
authors.initials: D
authors.lastname: Rahelic
authors.affiliation: Medical Director, Medical Centre "Aviva", Zagreb, Croatia.
authors.forename: Vida
authors.initials: V
authors.lastname: Demarin
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D001921:Brain / Q000187:drug effects*; D002317:Cardiovascular Agents / Q000494:pharmacology*; D002560:Cerebrovascular Circulation / Q000187:drug effects*; D003924:Diabetes Mellitus, Type 2 / Q000188:drug therapy* / Q000503:physiopathology; D005260:Female; D005500:Follow-Up Studies; D006439:Hemodynamics; D006801:Humans; D006935:Hypercapnia; D007213:Indomethacin / Q000494:pharmacology*; D008297:Male; D008875:Middle Aged; D020768:Middle Cerebral Artery / Q000187:drug effects*; D011379:Prognosis; D011446:Prospective Studies; D017585:Ultrasonography, Doppler, Transcranial; D055815:Young Adult
chemical_list: D002317:Cardiovascular Agents; D007213:Indomethacin