The effect of I.V. L-N^G Methylarginine Hydrochloride (L-NMMA: 546C88) on Basal and Acetazolamide (Diamox®) induced Changes of Blood Velocity in Cerebral Arteries and Regional Cerebral Blood flow in Man

Abstract

The aim of this study was to estimate the effect of Nitric Oxide synthase (NOS)-inhibition (L-NMMA) on the diameter of the middle cerebral artery (MCA) and on regional cerebral blood flow (rCBF). Furthermore, to assess the effect of L-NMMA on acetazolamide induced increases in MCA blood velocity (Vmean) and rCBF. In an open crossover design 12 healthy subjects attended the laboratory twice. The first day 6 mg/kg L-LNMMA i.v. over 15 min preceded 1 g acetazolamide i.v. over 5 min. Eight days later only acetazolamide was given. V(mean) in MCA was determined with transcranial Doppler (TCD) and rCBF with Xe-133 inhalation SPECT at baseline, after L-NMMA and 25 and 55 min after acetazolamide infusion. After L-NMMA the decrease in rCBF(MCA) was 6.8% (+/- 7.4) (P < 0.019, n = 12), whereas V(mean) was not affected (P = 0.83, n = 8). The change in MCA diameter was estimated to - 1.3% (P = 0.44, n = 8). L-NMMA did not affect acetazolamide increases in Vmean (P = 0.67, n = 8) nor rCBF (P = 0.29, n = 12). The percentage increase of V(mean) was 1.5 times that of rCBF (n = 8). Our data suggest that the basal tone of human cerebral arterioles but not of conduit arteries is NO-dependent. The action of acetazolamide in man is not NO-dependent.