[The Nitric Oxide System in a Chronic Deficiency of Mesostriatal Dopamine: the Action of Nitroglycerin]

Unilateral chronic deficiency in dopamine was induced by injection of the neurotoxin 6-hydroxydopamine into the mesostriatum of male Wistar rats (n = 15). The content of the nitric oxide metabolite--NO2- was three time less than in controls in the neostriatum on the operated side only, whereas, in the heart, aorta and plasma it was reduced by 1.9, 1.7 and 3.2 times, respectively. Four hours after subcutaneous injection of nitroglycerin (10 mg/kg, n = 4), a significant 6 fold increase in NO2- content in the neostriatum in the operated hemisphere and 2 fold increase on the in the intact side was observed. In heart, aorta and plasma NO2- content increased 2, 9, 3 times, respectively. The same dose of nitroglycerin given to intact rats (n = 4) had less effect on NO2- content: a 2 fold increase in heart, aorta and plasma only. Activity of NO-synthase (NOS) in animals with dopamine deficiency was reduced 2.7 fold in the neostriatum of the operated hemisphere and by 1.8 time on the intact side, in heart and aorta--by 1.8 and 3 time, respectively. Injection of nitroglycerin increased activity of NOS in the neostriatum of the operated hemisphere 2 fold and on the intact side 3 time; in heart (11 time) and aorta (1.3 time) after 4 hours. Similarly subcutaneous nitroglycerin injection restored the reduced endothelium-dependent vasodilator responses characteristic of the rats with mesostriatal dopamine deficiency. Thus the amplitude of acetylcholine-induced smooth muscles relaxation of the aorta increased by more than 70%. In these animals the injection of nitroglycerin also exerted a normalizing effect on the characteristic apomorphine-induced behaviour asymmetry (rotatory movements). On week after the injection of nitroglycerin the rotatory behaviour was reduced by 20.7% of control rotations. We show that nitroglycerin, a NO-donor, is a useful drug. It correct the abnormalities in the metabolic pathways on NO synthesis in a variety of tissues, endothelium-derived vascular responses and also the behaviour abnormalities induced by unilateral mesostriatal lesions. Our experimental animals are thought to be a model of human hemi-Parkinsonism. Thus nitroglycerin might be of use in Parkinson's disease.