Patologìâ (Dec 2019)
The features of the nitric oxide system in the left ventricle myocardium in the rats with experimental intermittent hypoxia of different duration
Abstract
The aim was to determine the features of the NO system status in the left ventricular myocardium in the rats with intermittent hypoxic hypobaric hypoxia during 15 and 60 days. Material and methods. The study was conducted on the 30 Wistar male rats, which were divided into 3 experimental groups: the 1st – control, the 2nd – rats exposed to intermittent hypoxia during 15 days and the 3rd group – the rats exposed to intermittent hypoxia during 60 days. Blood pressure was measured in all the rats. The objects and methods of the study were blood plasma (nitrotyrosine detection with immunoassay) and the myocardium of the left ventricle (concentration of nitrites by Griess nitrite test and content of immunoreactive material to the nitric oxide synthase isoforms by immunofluorescence method). mRNA expression of NOS isoforms was determined by PCR-RT method in the myocardium. Results. In the rats with 15-day hypoxia there was an increase in systolic pressure compared to control, and in 60-day hypoxia, there was also an increase in diastolic pressure although this changes were within the normotensive range. mRNA to all the myocardial NOS isoforms was characterized by an increase in both hypoxia groups. At the same time, the indices of the immunoreactive material content to the NOS isoforms were dependent on the hypoxia term. The concentration of the nitrotyrosine increased in both hypoxic groups, but in the long term it occurred along with a decrease in the level of nitrite, which indicates the possibility of nitro-oxidative stress. Conclusions. The 15-day intermittent hypoxia changes the myocardial NO system: an increase in the expression of all 3 isoforms, an increase in the nitrite and the nitrotyrosine content. iNOS becomes the predominant form of the enzyme in the myocardium with the increasing its mRNA. In 60-day hypoxia, the profile of the NOS enzyme is characterized by increased expression of the constitutive isoforms and decreased inducible NOS expression that was accompanied with significant increase in mRNA of all three forms. The level of terminal metabolites of NO was characterized by a decrease in the nitrite while the content of the nitrotyrosine increased.
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