1. We studied the effects of NG‐nitro‐L‐arginine (NOLA), a potent inhibitor of the L‐arginine‐nitric oxide pathway, and L‐arginine, the precursor of nitric oxide, on regional cerebral blood flow, electrocortical activity and ex vivo cerebrovascular reactivity in the cat. Flow was measured via radiolabelled microspheres, and vascular responses were studied by measuring isometric tension of isolated middle cerebral arterial rings. 2. NOLA (30 mg kg‐1 bolus followed by 1 mg kg‐1 min‐1 infusion) caused an approximately 40 mmHg elevation in the mean arterial blood pressure, a regionally heterogenous increase of the regional cerebrovascular resistance and a decrease in the regional cerebral blood flow 15 and 40 min after the start of its administration. In contrast L‐arginine (30 mg kg‐1 bolus followed by 10 mg kg‐1 min‐1 infusion) did not alter blood pressure, cerebrovascular resistance nor regional cerebral blood flow 15 min after the start of its administration. The NOLA‐induced changes in tissue flow were the most pronounced in the cerebellum, pituitary and medulla oblongata, whereas there was no decrease in the flow of the cortex and white matter. 3. NOLA caused characteristic changes in total fronto‐occipital EEG power and in power spectra which were unlikely to have been due to cerebral ischaemia. In addition, the ex vivo reactivity of the middle cerebral arteries showed signs of impaired endothelial nitric oxide synthesis: there were enhanced noradrenaline‐induced contractions and N‐ethoxycarbonyl‐3‐morpholino‐sydnonimine (SIN‐1)‐induced relaxations and markedly attenuated acetylcholine‐ and ATP‐induced relaxations after NOLA treatment. 4. The present data indicate that resting cerebral blood flow and cerebrovascular resistance are regulated by nitric oxide derived from L‐arginine in a regionally heterogenous way and that exogenous L‐arginine availability is not a limiting factor in this nitric oxide generation. Possibly, both the vascular endothelium and the neurons contribute to this basal nitric oxide release.
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