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Am J Physiol Regul Integr Comp Physiol 276: R1661-R1667, 1999;
0363-6119/99 $5.00
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Vol. 276, Issue 6, R1661-R1667, June 1999

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

Barbara Kiss1, Susanne Dallinger1, Oliver Findl2, Georg Rainer2, Hans-Georg Eichler1, and Leopold Schmetterer1,3

1 Departments of Clinical Pharmacology and 2 Ophthalmology and 3 Institute of Medical Physics, University of Vienna, A-1090 Vienna, Austria

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.

acetazolamide; cerebral blood flow; ocular blood flow; acidosis


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