Nitric oxide modulates cerebral blood flow stimulation by acetazolamide in the rat cortex: a laser Doppler scanning study.
The involvement of nitric oxide (NO) in cerebral blood flow (CBF) stimulation by acetazolamide was studied in anaesthetised, mechanically ventilated Wistar rats. CBF was monitored by laser Doppler scanning. Acetazolamide induced a long-lasting significant rCBF-increase. Application of NG-Nitro-L-arginine (L-NNA), an inhibitor of all NO synthetases (NOS), prevented CBF stimulation by acetazolamide. Continuous infusion of the exogenous NO donor SIN-1 (3-morpholinosydnonimine) suppressed L-NNA induced increases of mean arterial blood pressure without effect on rCBF in comparison to baseline. Additional acetazolamide injection then again caused a significant increase of rCBF in spite of NOS-inhibition. We thus conclude that NO is involved in acetazolamide-induced CBF stimulation. The mere continuous presence of NO is sufficient to re-establish the acetazolamide-response in spite of NOS-inhibition. These data suggest that NO acts rather as a modulator than as a mediator of the acetazolamide-induced CBF response.
Tuettenberg
J
J
Institute for Neurosurgical Pathophysiology, Johannes Gutenberg-University Mainz, Langenbeckstrasse 1, D-55101, Mainz, Germany.
Heimann
A
A
Kempski
O
O
D000086:Acetazolamide / Q000494:pharmacology*; D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D002257:Carbonic Anhydrase Inhibitors / Q000494:pharmacology*; D002540:Cerebral Cortex / Q000098:blood supply*; D002560:Cerebrovascular Circulation / Q000187:drug effects; D017078:Laser-Doppler Flowmetry; D008297:Male; D008981:Molsidomine / Q000031:analogs & derivatives* / Q000494:pharmacology; D009569:Nitric Oxide / Q000378:metabolism*; D020030:Nitric Oxide Donors / Q000494:pharmacology; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors; D019335:Nitroarginine / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D014665:Vasodilator Agents / Q000494:pharmacology*
D002257:Carbonic Anhydrase Inhibitors; D020030:Nitric Oxide Donors; D014665:Vasodilator Agents; D019335:Nitroarginine; D009569:Nitric Oxide; C002385:linsidomine; D008981:Molsidomine; D019001:Nitric Oxide Synthase; D000086:Acetazolamide