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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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