THE INFLUENCE OF CALCITRIOL ON THE PRODUCTION OF HYDROGEN SULFIDE IN THE CARDIOVASCULAR SYSTEM OF RATS
DOI:
https://doi.org/10.11603/mcch.2410-681X.2023.i3.14002Keywords:
hydrogen sulfide, metabolism, vitamin D, calcitriol, aorta, myocardium, ratsAbstract
Introduction. Vitamin D status disturbances are independent factor of high cardiovascular risk, arterial hypertension, coronary sclerosis, myocardial infarction. The active form of vitamin D (calcitriol) has been shown to be directly involved in the regulation of proliferation, cell adhesion, and membrane transport in the cardiovascular system. Some studies have demonstrated the booster effect of vitamin D on the level of the multifunctional gas mediator hydrogen sulfide (H2S) in tissues. However, the involvement of calcitriol in the regulation of various H2S metabolism pathways in the heart and blood vessels has not been definitively clarified and requires further investigation.
The aim of study – to determine the effect of calcitriol on different H2S metabolism pathways in the myocardium and aorta of rats.
Research Methods. The experiments were performed on 105 white male laboratory rats in accordance with the principles of bioethics. Calcitriol (1.25 (OH)2D3) was administered intragastrically in doses of 0.1 μg/kg and
1.0 μg/kg of rat body weight for 4 weeks. Control rats received equivolume amounts of the solvent. In the aorta and myocardium homogenates were determined H2S level and the activity of H2S metabolism enzymes. The expression of the cystathionine-γ-lyase (CSE) gene was determined using the method of quantitative real-time PCR (qRT-PCR). Statistical analysis of the results was performed using MS Excel and IBM Statistics SPSS 26 for Windows. The significance of the differences was assessed by the Mann-Whitney U test at a significance level of p<0.05.
Results and Discussion. Calcitriol induced multi-vector changes in H2S metabolism in the cardiovascular system depending on the dose and duration of use. 1.25 (OH)2D3 in a dose of 0.1μg/kg caused an increase in the level of H2S in the aorta and myocardium of rats and elevated the activity of enzymes of synthesis and utilization of H2S during the 4 weeks of the experiment. 1,25 (OH)2D3 at a dose of 1 μg/kg caused an increase in the level of H2S in the aorta and myocardium during the first 14 days, but subsequently had a depressing effect on the enzymes of H2S metabolism and caused a decrease in the level of H2S in rat myocardium and aorta. 1,25 (OH)2D3 had an effect on CSE gene expression in the aorta and myocardium of rats with a stimulating effect at a dose of 0.1 μg/kg and an inhibitory effect at a dose of 1 μg/kg.
Conclusions. Calcitriol acts as a regulator of different H2S metabolism pathways in the cardiovascular system of rats: in high doses, 1,25 (OH)2D3 significantly inhibits the activity of H2S-synthesizing enzymes and enzymes of H2S utilization in the aorta and myocardium, while at physiological concentrations, it stimulates H2S production. The phenomenon of influence of 1.25 (OH)2D3 on the H2S system is important for determining the strategy of preventing cardiovascular diseases according to varying vitamin D3 status.
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