Effect of inhibition of nitric oxide synthase on dynamic cerebral autoregulation in humans

Cerebral blood flow is maintained constant over a range of cerebral perfusi on pressures by cerebral autoregulation. Impaired cerebral autoregulation m ay be important in the pathogenesis of cerebral ischaemia. The mechanisms m ediating normal cerebral autoregulation in humans are poorly understood. We used a recently described transcranial Doppler technique, which allows non -invasive measurement of dynamic cerebral autoregulation, to test the hypot hesis that nitric oxide mediates cerebral autoregulation. The rate of rise of middle cerebral artery blood flow velocity, compared with that of arteri al blood pressure, was determined following a stepwise fall in arterial blo od pressure, in order to calculate an autoregulatory index. The effect of t he nitric oxide synthase inhibitor N-G-monomethyl-L-arginine (L-NMMA) on dy namic autoregulation was compared with that of noradrenaline titrated to re sult in a similar rise in blood pressure. Six healthy subjects were studied in each group. The mean (S.D.) change in autoregulatory index following no radrenaline at a similar presser dose was significantly greater than the ch ange following the L-NMMA bolus: 1.1 (1.2) compared with -0.8 (0.8) for the left middle cerebral artery (P = 0.002), and 1.1 (0.8) compared with -0.8 (0.8) for the right middle cerebral artery (P = 0.002). There was no differ ence in the mean (S.D.) blood pressure increase resulting from the two agen ts: L-NMMA, 19.7 (7.4) mmHg; noradrenaline, 15.5 (4.8) mmHg (P = 0.281). Th ese results suggest that nitric oxide mediates at least part of the dynamic phase of cerebral autoregulation in humans. Reduced nitric oxide release m ay play a role in the impaired cerebral autoregulation seen in patients wit h, or at risk of, cerebral ischaemia.