Acetazolamide induces indomethacin and ischaemia-sensitive pial arteriolar vasodilation in the piglet.
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.
Domoki
Ferenc
F
Department of Physiology, University of Szeged, Szeged, Hungary. fdomoki@wfubmc.edu
Zimmermann
Aliz
A
Tóth-Szuki
Valéria
V
Busija
David W
DW
Bari
Ferenc
F
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*
D002257:Carbonic Anhydrase Inhibitors; D002317:Cardiovascular Agents; D000086:Acetazolamide; D007213:Indomethacin