[The nitrous oxide system under conditions of chronic cerebral dopamine deficiency and hypoxia]

Acute experiments were conducted on adult Wistar rats two months after unilateral microinjection of the 6-hydroxydopamine into the medial forebrain bundle. This led to a greater than 90% decrease of dopamine, fell by 70% of the content of the stable metabolite of nitric oxide-nitrite anion and by up to 80% of nitric oxide synthase activity in the lesioned neostriatum. Nitric oxide synthase activity fell by 30% in the heart, by 60% in the aorta, while nitrite anion decreased in the heart and aorta, in blood plasma and erythrocytes by 45%, 40%, 70%, 30% compared with controls rats, respectively. Lesioned rats also showed changes in the pattern of responses of the smooth muscle of the aorta predominantly to endothelium-dependent (acetylcholine), rather than to endothelium-independent (nitroprusside) vasoreactivity. The amplitude of acetylcholine-induced relaxation of aortic smooth muscle decreased 4-fold, the rate of this response decreased 5-fold and the latent period increased 4-fold. Exposure of lesioned rats, controls rats to moderate hypoxia for 30 min resulted in a rise of nitrite anion content in all tissues; it increased 2-fold in erythrocytes of lesioned rats vs controls rats, in the lesioned and unlesioned neostriatum hypoxia restored the values to controls, while in the heart, aorta and plasma the levels were also increased but did not reach control values. Hypoxia also led to a rise of nitric oxide synthase activity in both lesioned rats and controls rats. However, compared to normoxia, the levels increased over 2 times in the lesioned neostriatum and in the heart, whereas in controls the increase was less that 2-fold. Hypoxia resulted in partial normalization of the functional deficit in endothelium-dependent dilatory responses of aortic smooth muscle. We conclude that the disturbances in nitric oxide system induced by mesostriatal dopaminergic lesions in animals may have relevance to Parkinson's disease. The improvement with ambient hypoxia in quantitative and functional aspects of the disturbances in nitric oxide system may also have relevance in the management of the disease.