MECHANISMS OF COMMUNICATION BETWEEN CENTRAL NERVOUS SYSTEM AND KIDNEY IN EXPERIMENTAL DIABETES MELLITUS

Abstract

Diabetes mellitus (DM) is a syndrome with multiple etiology characterized by the presence of inappropriate hyperglycemia caused by lack of insulin and/or its failure to properly exercise its effects. The impact of the disease as a public health problem stems not only from their clinical problems directly related to hyperglycemia, but mainly by the functional changes that occur in different organs and systems, resulting from chronic metabolic disorder. These complications, it is noteworthy that diabetic nephropathy is the most common etiology of chronic kidney disease in Western countries being associated with the highest mortality rate. In the model streptozotocin-induced diabetic rats has been shown that renal sympathetic nerve activity is paradoxically enhanced in relation to other areas of the body. It is also known that this model of DM has increased oxidative stress and activation of the renin-angiotensin system (RAS) and that these factors may be involved in autonomic dysfunction in DM. Therefore, this project aims to assess the level of sympathetic postganglionic basal activity (tonic and reflex) of renal and lumbar nerves and their correlation with the activity of the phrenic nerve, since the respiratory activity strongly influences vasomotor sympathetic activity. In this way, we intend to investigate whether there is is a topographic or preferred setting of sympathetic vasomotor activity and respiratory drive in DM. At the same time, will be evaluated the glutamatergic and angiotensinergic actions in rostral ventrolateral medulla, considered one of the most important regions of the brain involved in the control of sympathetic vasomotor activity. In addition, we will evaluate the renal and central oxidative stress and RAS by molecular biology approaches. In another series of experiments we will investigate the role of renal denervation in the sympathetic balance, cardiovascular, oxidative stress and metabolic parameters in control and diabetic rats. Thus, we aimed to improve understanding of the various mechanisms involved in the sympathetic vasomotor autonomic control in DM.