Acetazolamide-induced cerebral and ocular vasodilation in humans is independent of nitric oxide

Acetazolamide, a carbonic anhydrase inhibitor, is used orally in the treatm ent of primary and secondary open-angle glaucoma and induces ocular and cer ebral vasodilation. Several in vitro studies have shown that carbonic anhyd rase pharmacology and the L-arginine-nitric oxide (NO) pathway are closely related. We investigated the role of NO in acetazolamide-induced vasodilati on 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. Acetazolami de was administered after pretreatment with either L-NMMA or placebo and ei ther L-arginine or placebo. Pulsatile choroidal blood flow was assessed wit h laser interferometric measurement of fundus pulsation. In addition, mean blood flow velocity (MFV) in the middle cerebral artery (MCA) and ophthalmi c artery (OA) was measured with Doppler sonography. Acetazolamide increased ocular fundus pulsation amplitude (FPA; +27%, P < 0.001) and MFV in the MC A (+38%, P < 0.001) and in the OA (+ 19%, P = 0.003). Administration of L-N MMA 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 acet azolamide-induced changes in cerebral or ocular hemodynamic parameters. The present data indicate that acetazolamide-induced hemodynamic changes are n ot mediated by NO. Which mediators other than NO are involved in the hemody namic effects as induced by carbonic anhydrase inhibitors remains to be elu cidated.