Overproduction of nitric oxide in animals with streptozotocin diabetes mellitus is down-regulated by dihydropiridines

Abstract

Diabetes mellitus (DM) and its complications cause numerous health and social problems throughout the world. Pathogenic action of nitric oxide (NO) is responsible to a large extent for development of complications of the disease. Thus search for compounds modifying NO production in DM patients appears to be important for development of pharmacological remedies for treatment of DM complications. Dihydropiridines (DHP) appear to be prospective compounds from this point of view. The goal of the present work was to study alterations of NO production in streptozotocin model of DM in rats and ability of several DHPs and to normalize NO synthesis. Production of nitric oxide was monitored by means of ESP spectroscopy of Fe–DETC–NO complex. Development of streptozotocin diabetes was followed by increase of NO production in the liver, kidneys, blood and muscles. In adipose tissue changes in NO production were adverse. Cerebrocrast treatment (0.5 mg/kg per os for 3 days) was followed by normalization of NO production in the liver, kidneys and blood. Another DHP etaftoron administered in similar dose was effective in kidneys, blood and muscles. Fenaftoron decreased NO production in the liver of diabetic animals and also kidneys, blood and muscles. Elucidation of the DHP action site in the mechanism of the NO production will be the goal of our future studies. As the studied DHP are Ca 2+ channel blockers constitutive NO synthases seem to be most the likely candidates for targets of these drugs. The work was supported by the Program 2010.10.-4/VPP4 and ERAF Project No. 2010/0202/2DP/2.1.1.2.0/10/APIA/VIAA/013.