Acetazolamide-induced cerebral and ocular vasodilation in humans is independent of nitric oxide.
Acetazolamide, a carbonic anhydrase inhibitor, is used orally in the treatment of primary and secondary open-angle glaucoma and induces ocular and cerebral vasodilation. Several in vitro studies have shown that carbonic anhydrase pharmacology and the L-arginine-nitric oxide (NO) pathway are closely related. We investigated the role of NO in acetazolamide-induced vasodilation on cerebral and ocular vessels in 12 healthy subjects in the presence or absence of NG-monomethyl-L-arginine (L-NMMA), a NO synthase inhibitor, and in the presence or absence of L-arginine, the precursor of NO. Acetazolamide was administered after pretreatment with either L-NMMA or placebo and either L-arginine or placebo. Pulsatile choroidal blood flow was assessed with laser interferometric measurement of fundus pulsation. In addition, mean blood flow velocity (MFV) in the middle cerebral artery (MCA) and ophthalmic artery (OA) was measured with Doppler sonography. Acetazolamide increased ocular fundus pulsation amplitude (FPA; +27%, P < 0.001) and MFV in the MCA (+38%, P < 0.001) and in the OA (+19%, P = 0.003). Administration of L-NMMA alone reduced FPA (-21%, P < 0.001) and MFV in the MCA (-11%, P = 0. 030) but did not change MFV in the OA. All hemodynamic effects of L-NMMA were reversed by L-arginine. However, neither L-NMMA nor L-arginine altered acetazolamide-induced changes in cerebral or ocular hemodynamic parameters. The present data indicate that acetazolamide-induced hemodynamic changes are not mediated by NO. Which mediators other than NO are involved in the hemodynamic effects as induced by carbonic anhydrase inhibitors remains to be elucidated.
Kiss
B
B
Departments of Clinical Pharmacology, University of Vienna, A-1090 Vienna, Austria.
Dallinger
S
S
Findl
O
O
Rainer
G
G
Eichler
H G
HG
Schmetterer
L
L
D000086:Acetazolamide / Q000494:pharmacology*; D000328:Adult; D001120:Arginine / Q000494:pharmacology; D001808:Blood Vessels / Q000502:physiology; D002257:Carbonic Anhydrase Inhibitors / Q000494:pharmacology*; D002560:Cerebrovascular Circulation / Q000187:drug effects* / Q000502:physiology*; D018592:Cross-Over Studies; D004311:Double-Blind Method; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005123:Eye / Q000098:blood supply*; D006801:Humans; D009569:Nitric Oxide / Q000502:physiology*; D014664:Vasodilation / Q000502:physiology*; D019323:omega-N-Methylarginine / Q000494:pharmacology
D002257:Carbonic Anhydrase Inhibitors; D004791:Enzyme Inhibitors; D019323:omega-N-Methylarginine; D009569:Nitric Oxide; D001120:Arginine; D000086:Acetazolamide