Abstract

The aim was to determine the pathogenetic features of the NO system in the myocardium of the left ventricle in the rats with endocrine-salt hypertension.Material and methods. The experiment was conducted on 20 male rats 220-290 g weight, 6–10 months old which were divided into 2 experimental groups: 1st – the control group (10 intact normotensive male Wistar rats); 2nd – 10 male Wistar rats with endocrine-salt arterial hypertension. Systolic and diastolic BP levels were measured in all the rats using a system of non-invasive arterial pressure measurement BP-2000. The objects of study in the experimental animals were blood plasma in which the nitrotyrosine level was measured, and the fragment of left ventricle, which was divided into two parts, one of which was homogenized using a Silent Crusher S homogenizer (Heidolph, Germany), in which nitrites level was determined. Concentration of immunoreactive material to NOS isoforms was detected with immunofluorescence method. The study of NOS mRNA isoforms expression in the left ventricular myocardium homogenates was carried out using a real-time polymerase chain reactionResults. In the experiment, an increase in all 3 isoforms and their mRNA was obtained. In the study, a decrease in nitrites concentration and a significant increase in nitrotyrosine levels, indicates the development of nitroso-oxidative stress.Conclusions. The development of experimental endocrine-salt hypertension in the Wistar rats leads to a stable increase in mean blood pressure by 65 % compared to control. Endocrine-salt arterial hypertension in Wistar rats is characterized by an increased mRNA content of all three isoforms of nNOS, eNOS and iNOS by 2.7, 2.8 and 5.7 times, respectively, compared to the control; increased expression of immunoreactive material to isoforms in transverse fibers by 14.3 %, 16.2 % and 18.5 %, respectively; in longitudinal fibers IRM to nNOS was higher by 8.3 %, to iNOS - by 8. 5%, but to eNOS it was lower by 7.6 %. At the same time, nitrites level decreased by 11.7 % and nitrotyrosine concentration was significantly higher, exceeding the control value by 88.5 %.

Highlights

  • According to the WHO, every third adult in the world suffers from arterial hypertension (AH)

  • Endocrine-salt arterial hypertension in Wistar rats is characterized by an increased mRNA content of all three isoforms of nNOS, eNOS and iNOS by 2.7, 2.8 and 5.7 times, respectively, compared to the control; increased expression of immunoreactive material to isoforms in transverse fibers by 14.3 %, 16.2 % and 18.5 %, respectively; in longitudinal fibers IRM to nNOS was higher by 8.3 %, to iNOS - by 8. 5%, but to eNOS it was lower by 7.6 %

  • The study of mRNA expression of nitric oxide synthase (NOS) isoforms by PCR-RT showed that hypertension leads to a significant increase in mRNA to all three NOS isoforms with the highest values of iNOS mRNA (Fig.1В)

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Summary

Introduction

According to the WHO, every third adult in the world suffers from arterial hypertension (AH). Secondary hypertension accounts for 5-10 % of all identified causes of persistent hypertension, among them hypercorticism and hyperaldosteronism lead to the development of AH in 70-85 % of patients over 40 years of age [1]. It should be noted that in patients with hypercorticism combination of high cortisol levels with increased secretion of mineralocorticoids is observed. The pathogenesis of persistent hypertension caused by steroid hyperproduction is primarily related to their effects on glucocorticoid (GRs) and mineralocorticoid renal receptors (MRs), that leads to increased sodium reabsorption, water retention and potassium excretion. Cortisol usually interacts with the MRs receptor as an antagonist in the sense that it binds to it but does not activate it. Especially in the case of superoxide formation, it becomes an agonist of MRs, mimicking the action of aldosterone [2]

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