The effect of the nitric oxide synthase inhibitor L-NMMA on basal CBF and vasoneuronal coupling in man: a PET study

Nitric oxide (NO) regulates basal CBF. In a number of animal models NO has been implicated in the mediation of the regional changes in CBF (rCBF) that accompany neuronal activation (vasoneuronal coupling). However, some resul ts in animal models have failed to confirm this finding, and the validity o f extrapolation to man from animal data is uncertain. To determine the cont ribution of NO to basal global CBF and activation-induced changes in rCBF, the authors have performed quantitative (H2O)-O-15 positron emission tomogr aphy (PET) studies before and after administration of the non-isoform-speci fic NO synthase inhibitor, N-G-monomethyl-L-arginine (L-NMMA), in 10 health y male volunteers. Learning a novel sequence of finger movements was used a s a paradigm to induce regional frontal cortex activation. The effect of NO synthase inhibition on the magnitude and pattern of activation was determi ned. Resting global CBF fell from 33.3 +/- 5.3 mL.100 g(-1).min(-1) at rest before L-NMMA, to 26.5 +/- 7.7 mL.100 g(-1).min(-1) after L-NMMA (P = 0.00 1). This fall was reversed by L-arginine administration. Learning sequentia l finger movements induced increases in rCBF in the left motor, right prefr ontal, and bilateral premotor cortices. After NO synthase inhibition with L -NMMA, there was no change in this pattern of activation and no reduction i n the magnitude of rCBF responses at the foci of maximal stimulation before and after L-NMMA. These findings confirm that NO production contributes to basal CBF regulation in man, but show that systemic NO synthase inhibition with L-NMMA does not impair regional vasoneuronal coupling.