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Title: New methods in the treatment of endothelial dysfunction in animal model of pulmonary hypertension – trial of efficacy


Aims of this work: (1) description of relationships between main endothelial mediators: prostacyclin(PGl)/thromboxane, nitric oxide (NO), endothelin-1 (ET-1) and histopathological, morphometrical and functional changes of pulmonary circulation and heart in rats 1, 2, and 4 weeks after MCT-injection (MCT, 60 mg/kg s.c.); (2) analysis of efficacy of treatment with MNA (1-methyl-nicotinatmide) on selected endothelial dysfunction indices and selected functional and morphometrical changes in heart 2 and 4 weeks after MCT injection. To investigate functional changes of pulmonary circulation in isolated perfused rat lung estimation of endothelial function obtained by analysis of the magnitude of NO-dependent attenuation of hypoxic pulmonary vasoconstriction (HPV) was used. To analyze functional changes of heart magnetic resonance imagination (MRI) method was used. Histopathological and ultrastructural changes in lung tissue after MCT was also studied. Changes of HPV, support with plasma levels of PGl2, ADMA and ET-1 allowed to classified the level of endothelial dysfunction in first two weeks after MCT injection. Ultrastructural but not histopathological changes of lung tissue were also observed at this time. Four weeks after MCT administration functional changes in pulmonary circulation and biochemical parameters were aggravated and measured with MRI hemodynamical ; changes of heart, were observed. Treatment with MNA added to ETA receptor antagonist reversed endothelial dysfunction measured in isolated perfused rat lung in second week and diminished right ventricular hypertrophy in fourth week after MCT administration. This treatment partly inhibited MCT induced pulmonary hypertension in rats.

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Level of degree:

2 - studia doktoranckie

Degree discipline:

choroby układu krążenia ; farmakologia

Degree grantor:

Wydział Farmaceutyczny


Chłopicki, Stefan

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tylko w bibliotece

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Last modified:

Mar 9, 2023

In our library since:

Nov 21, 2012

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Edition name Date
ZB-113477 Mar 9, 2023


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