NITRIC-OXIDE SYNTHASE INHIBITION IN HUMANS REDUCES CEREBRAL BLOOD-FLOW BUT NOT THE HYPEREMIC RESPONSE TO HYPERCAPNIA

Background and Purpose-Animal studies suggest that nitric oxide (NO) i s important in basal cerebral blood now (CBF) regulation and that it m ay mediate the vasodilatory response to carbon dioxide. We investigate d its role in the human circulation using the NO synthase inhibitor NG -monomethyl-L-arginine (L-NMMA).Methods-L-NMMA was administered as an intravenous bolus at three doses (1, 3, and 10 mg/kg). CBF was assesse d by color velocity ultrasonic imaging of internal and common carotid artery volume now (ICA now and CCA now) and transcranial Doppler ultra sound measurement of middle cerebral artery now velocity (MCA nu). The presser effect of L-NMMA was controlled for by comparison with noradr enaline titrated to effect an equivalent blood pressure elevation. Res ults-L-NMMA produced a dose-dependent reduction in basal mean +/- SD C CA flow from 415.2 +/- 51.9 to 294 +/- 56.2 mL/min (at 10 mg/kg) and I CA now from 268.8 +/- 59.4 to 226.2 +/- 72.6 mL/min (P<.005 and P<.05, respectively, comparing areas under the dose-response curve). This wa s reversed by L-arginine. Mean +/- SD systemic blood pressure rose fro m 85.2 +/- 6.4 to 100.8 +/- 9.6 mm Hg (P<.01). There was no significan t reduction in MCA nu. There was no significant change in the CBF resp onse to either 6% or 8% carbon dioxide after L-NMMA. Noradrenaline pro duced a lesser fall in basal CCA flow (12.0%) but had a similar effect on the hypercapnic response. Conclusions-Basal NO release is importan t in controlling human CBF, but intravenously administered L-NMMA does not inhibit the hypercapnic hyperemic response in humans. The discrep ancy between CBF and MCA nu after L-NMMA administration is consistent with MCA vasoconstriction. Neuronal NO synthase inhibition may be prot ective in stroke. However, our results suggest that nonselective NO sy nthase inhibitors such as L-NMMA should be used with caution because t hey reduce CBF.