Cascade of acetazolamide-induced vasodilatation.
Acetazolamide (AZ) has been found to be effective in inducing vasodilatation. To evaluate the mechanism by which AZ acts, we compared the effects of this agent on vascular PGI2, endothelin (ET-1), and NOx, with those induced by CO2 gas inhalation.


METHODS
Blood flow (BF) was measured in the liver, kidneys, stomach wall, and abdominal muscle of anesthetized white rabbits with a laser flow meter at baseline and again after sequential doses of AZ (4 mg/kg) or CO2 inhalation. Cardiac output and serum concentrations of PGI2, ET-1, and NOx were also measured in these animals.


RESULTS
AZ increased BF in the liver and kidneys, but had no effect on BF in the stomach wall or abdominal muscle. The level of NOx was decreased following the administration of AZ, while PGI2 and ET-1 levels remained unchanged. In contrast, CO2 inhalation increased PCO2, and decreased pH, significantly. CO2 elevated BF in the liver, kidneys, stomach wall, and abdominal muscle, as well as serum levels of PGI2 and ET-1, while having no effect on NOx levels. The alterations in BF, PGI2, ET-1, and NOx in response to AZ, suggest that the mechanism of AZ-induced vasodilatation may involve a cascade that is triggered by CO2 retention similar to that caused by the inhalation of CO2.
Taki
K
K
Department of Emergency Medicine, Saga Medical College, Saga City, Japan.
Kato
H
H
Endo
S
S
Inada
K
K
Totsuka
K
K
D015121:6-Ketoprostaglandin F1 alpha / Q000097:blood; D000086:Acetazolamide / Q000494:pharmacology*; D000818:Animals; D001784:Blood Gas Analysis; D001794:Blood Pressure / Q000187:drug effects; D002245:Carbon Dioxide / Q000097:blood / Q000494:pharmacology; D002257:Carbonic Anhydrase Inhibitors / Q000494:pharmacology*; D002302:Cardiac Output / Q000187:drug effects; D019332:Endothelin-1 / Q000097:blood; D011464:Epoprostenol / Q000097:blood; D006863:Hydrogen-Ion Concentration / Q000187:drug effects; D007668:Kidney / Q000098:blood supply / Q000187:drug effects; D017078:Laser-Doppler Flowmetry; D008099:Liver / Q000098:blood supply / Q000187:drug effects; D018482:Muscle, Skeletal / Q000098:blood supply / Q000187:drug effects; D009569:Nitric Oxide / Q000097:blood; D010100:Oxygen / Q000097:blood; D011817:Rabbits; D012039:Regional Blood Flow / Q000187:drug effects*; D013270:Stomach / Q000098:blood supply / Q000187:drug effects; D014664:Vasodilation / Q000187:drug effects*
D002257:Carbonic Anhydrase Inhibitors; D019332:Endothelin-1; D002245:Carbon Dioxide; D009569:Nitric Oxide; D015121:6-Ketoprostaglandin F1 alpha; D011464:Epoprostenol; D000086:Acetazolamide; D010100:Oxygen