Inhibition of neuronal nitric oxide synthase by 7-nitroindazole: effects upon local cerebral blood flow and glucose use in the rat

Journal of Cerebral Blood Flow and Metabolism : Official Journal of the International Society of Cerebral Blood Flow and Metabolism
P A KellyG W Arbuthnott

Abstract

The novel nitric oxide synthase inhibitor 7-nitroindazole (7-NI) is relatively specific for the neuronal isoform of the enzyme and in this study we have used this compound to investigate the physiological role of perivascular nitric oxide-containing nerves in the cerebrovascular bed. Following injection of 7-NI (25 or 50 mg/kg, i.p.), cerebral blood flow and glucose utilization were measured in the conscious rat using the fully quantitative [14C]iodoantipyrine and 2-[14C]deoxyglucose techniques, respectively. Neither dose of the drug produced any change in arterial blood pressure, confirming a lack of effect upon the endothelial isoform of the enzyme, although there was a pronounced decrease in heart rate (-28% by 10 min postinjection). Throughout the brain 25 mg/kg 7-NI i.p. resulted in decreases in blood flow of between -20% in the hippocampus and -58% in the substantia nigra. Increasing the dose to 50 mg/kg resulted in a further generalized decrease, to almost -60% in parts of the thalamus and hippocampus, but in every animal this higher dose of 7-NI also produced randomly distributed areas of relative hyperaemia, which were most commonly found in those areas where the most intense hypoperfusion was otherwise in evidence. De...Continue Reading

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