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Combined pharmacotherapy of different types of pulmonary hypertension
Krása, Kryštof ; Hampl, Václav (advisor) ; Neckář, Jan (referee) ; Al-Hiti, Hikmet (referee)
Pulmonary hypertension is a group of diseases characterized by increased mean pulmonary artery pressure. Especially in group 2, which is associated with heart disease and is the most prevalent of all types, and in group 3, associated with lung disease, no sufficiently effective treatment has yet been developed beyond the treatment of the underlying disease, which is problematic in many cases. Dehydroepiandrosterone sulfate (DHEA S) and statins have different mechanisms of action on pulmonary hypertension in some respects, so the question of the effectiveness of combining them on pulmonary hypertension versus either agent alone has been offered. To test this hypothesis, we induced pulmonary hypertension in adult male rats by three weeks of exposure to hypoxia (10% O2) and treated them with simvastatin (60 mg/L) and DHEA S (100 mg/L) in drinking water, either alone or in combination. Both simvastatin and DHEA S reduced mean pulmonary artery pressure (from a mean ± s.d. value of 34.4 ± 4.4 to 27.6 ± 5.9 and 26.7 ± 4.8 mmHg, respectively), but their combination was not more effective (26.7 ± 7.9 mmHg). Differences in the degree of oxidative stress (as indicated by malondialdehydedehydplasma concentration), the degree of superoxide production (electron paramagnetic resonance) or blood nitric oxide...
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