title: Acetazolamide induces indomethacin and ischaemia-sensitive pial arteriolar vasodilation in the piglet.
abstract: OBJECTIVE
  Acetazolamide (AZD) produces cerebral vasodilation. The underlying mechanism is unclear, but it is assumed to be largely due to CO2 retention and acidosis. We tested if cerebrovascular effects of AZD were similar to hypercapnia in the newborn pig.
  
  
  METHODS
  We used the closed cranial window/intravital microscopy technique to determine pial arteriolar diameters simultaneously with laser-Doppler flowmetry (LDF) to monitor cortical blood perfusion. Anaesthetized (Na-thiopenthal +alpha-chloralose), ventilated, 1-day-old instrumented piglets (n=38) were divided into five experimental groups: time control (n=11), indomethacin, ibuprofen, Nomega-nitro-L-arginine methyl ester (L-NAME) treatments (1, 30, 15 mg/kg, i.v., n=6, 6, 4, respectively), and global ischaemia/reperfusion (I/R, 10 min induced by elevated intracranial pressure, n=11). Responses to 5-10% inhaled CO2 were recorded before and after the treatments, and then in a similar manner to AZD (10-20 mg/kg, i.v.).
  
  
  RESULTS
  Hypercapnia and AZD produced pial arteriolar vasodilation and increases in cortical perfusion. Consistent with previous data, hypercapnia-induced changes were abolished by indomethacin, unaltered by ibuprofen and L-NAME and were significantly attenuated after I/R. AZD-induced vasodilation was also sensitive to indomethacin and I/R and was unaltered by ibuprofen or L-NAME.
  
  
  CONCLUSIONS
  The mechanism of AZD-induced vasodilation appears to be similar/identical to hypercapnia, and pial arteriolar diameter changes reflect changes in cortical perfusion.
authors.affiliation: Department of Physiology, University of Szeged, Szeged, Hungary. fdomoki@wfubmc.edu
authors.forename: Ferenc
authors.initials: F
authors.lastname: Domoki
authors.forename: Aliz
authors.initials: A
authors.lastname: Zimmermann
authors.forename: Valéria
authors.initials: V
authors.lastname: Tóth-Szuki
authors.forename: David W
authors.initials: DW
authors.lastname: Busija
authors.forename: Ferenc
authors.initials: F
authors.lastname: Bari
mesh_terms: D000086:Acetazolamide / Q000494:pharmacology*; D000818:Animals; D000831:Animals, Newborn; D001160:Arterioles / Q000187:drug effects; D002257:Carbonic Anhydrase Inhibitors / Q000494:pharmacology*; D002317:Cardiovascular Agents / Q000494:pharmacology*; D005260:Female; D007213:Indomethacin / Q000494:pharmacology*; D007511:Ischemia / Q000503:physiopathology*; D017078:Laser-Doppler Flowmetry; D008297:Male; D010841:Pia Mater / Q000098:blood supply*; D013552:Swine; D014664:Vasodilation / Q000187:drug effects*
chemical_list: D002257:Carbonic Anhydrase Inhibitors; D002317:Cardiovascular Agents; D000086:Acetazolamide; D007213:Indomethacin