Effect of sustained norepinephrine infusion on local cerebral blood flow in the rat

In order to elucidate the possible role of noradrenergic hyperactivity in producing disturbances of cerebral circulation during hemorrhagic shock, the effect of prolonged norepinephrine infusion on local cerebral blood flow was studied in anesthetized and artificially ventilated rats. Intravenous infusion of 20 micrograms/(kg.min) norepinephrine for 2 hr produced circulatory shock characterized by progressive hypotension and acidosis. As a result, local cerebral blood flow, which was determined by autoradiography employing 14C-labeled iodoantipyrine in 79 different anatomical structures, decreased substantially in many areas. The most pronounced reductions were found in the regions supplied by the internal carotid artery, whereas the blood flow of the vertebral territory remained close to control. The blood supply of the cerebral cortex exhibited extreme heterogeneity with flow values below 0.10 ml/(min.gm). When either the intensity or the length of the infusion was reduced, no signs of circulatory breakdown could be observed. Variation of the infusion parameters demonstrated the dose-dependent nature of the cerebral blood flow response. Preinfusion blockade of alpha-receptors with 5 mg/kg phenoxybenzamine prevented the development of circulatory shock and reversed the decrease in cerebral blood flow induced by norepinephrine. The experimental results support the hypothesis that high concentration of norepinephrine in the vicinity of cerebral vessels produced by sympathetic hyperactivity might be an important factor in the etiology of blood flow deficiencies.