EFFECT OF OXACOM ON THE RIGHT VENTRICULAR PRESSURE IN RATS WITH MONOСROTALIN-INDUCED PULMONARY ARTERIAL HYPERTENSION

Background. Pulmonary arterial hypertension (PAH) is a relatively rare disease, but its therapy is expensive and effectiveness is moderate. One of important mechanisms of PAH pathogenesis is reduced formation of nitric oxide in pulmonary vascular endotheliocytes. Objective. To study the effect of oxacom (dinitrosyle iron complex with ligand glutathione), which already demonstrated long-term decline in blood pressure (BP) in systemic circulation, on pressure in pulmonary circulation. Design and method. To induce PAH, the standard monocrotalin rat model was used. Three weeks after monocrotalin introduction (60 mg/kg), a catheterization of the right ventricle was performed in anesthetized rats (100 mg/kg ketamine) through jugular vein and pressure was measured. Simultaneously, BP in femoral artery and ECG were recorded. Results. Systolic pressure in the right ventricle (SPRV) in rats after monocrotalin introduction doubled compared with the control group, from 35 to 70 mmHg, but myocardial contractility index fell by 28 %, also duration of QRS complex and the height of T-wave increased. Intravenous oxacom (40 mg/kg) quickly reduced SPRV by average of 12 ± 3 mmHg, and this level was maintained for an hour. This effect was absent in control rats. Similar BP changes in systemic circulation were observed in both groups. Inhalation of nitric oxide led to BP decrease only in animals with high level of SPRV. Inhalation of oxacom was ineffective. Conclusion. Oxacom is a promising substance for sustained pressure decline in the pulmonary circulation in PAH, but further investigations are needed for the development of a more suitable prolonged-action form of the drug.

pulmonary arterial hypertension, nitric oxide, monocrotalin, dinitrosyle iron complexes, blood pressure

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