Talanov S. Changes in functional state of the cardiovascular system in rats with chronic deficiency of nigrostriatal dopamine

In the dissertation, the priority experimental data have been obtained of the direct effects of chronic deficiency of cerebral dopamine resulted from a destruction of nigrostriatal dopaminergic system on cardiovascular dysfunctions. In experiments on isolated vascular preparations, an impairment of endothelium dependent relaxation in the aorta smooth muscle was shown together with a decrease in an increment of amplitude of phase contractions on preliminary elongation of the vena cava, and an increase in a rigidity of the vascular wall. In experiments on isolated heart preparations, deterioration of the contractile functioning of the heart has been shown: an endurance of the cardiac muscle to elongation reduced, and diastolic rigidity of the myocardium increased. It has been cleared up that functional changes in the heart were due to worsening of the myocardial mitochondria function, namely, an increase in the sensitivity of the mitochondrial permeability transition pore to its natural inductor calcium. In biochemical studies, it has been shown that oxidative stress developed in the tissues of the cardiovascular system of the rats with chronic deficiency of nigrostriatal dopamine, an intensity of generation of reactive oxygen species increased, and lipid peroxidation activated. In addition, in those animals we observed changes in nitric oxide (NO) synthesis: an activity of constitutive calcium-dependent NO synthases decreased, but an activity of inducible NO synthase, independent on calcium level, increased, together with an increased arginase way of L-arginine degradation.