MITOCHONDRIAL OXIDANT STRESS INCREASES PDE5 ACTIVITY IN PERSISTENT PULMONARY HYPERTENSION OF THE NEWBORN
| Autor: | Kathryn N. Farrow, Lyubov Czech, Sylvia F. Gugino, Paul T. Schumacker, Keng Jin Lee, Satyanarayana Lakshminrusimha, Robin H. Steinhorn, Stephen Wedgwood |
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| Jazyk: | angličtina |
| Rok vydání: | 2010 |
| Předmět: |
Physiology
medicine.disease_cause Persistent Fetal Circulation Syndrome Polyethylene Glycols chemistry.chemical_compound Pregnancy Medicine Cyclic GMP Cells Cultured Hyperoxia Immunoassay biology General Neuroscience Goats Catalase Mitochondria Anesthesia Breathing Female medicine.symptom Pulmonary and Respiratory Medicine medicine.medical_specialty Myocytes Smooth Muscle Pulmonary Artery Nitric Oxide Article Nitric oxide Internal medicine medicine.artery Animals Humans business.industry Infant Newborn medicine.disease Embryo Mammalian Pulmonary hypertension Oxygen Disease Models Animal Oxidative Stress Endocrinology chemistry Animals Newborn Gene Expression Regulation Pulmonary artery biology.protein business Reactive Oxygen Species Oxidative stress |
| Popis: | In the pulmonary vasculature, phosphodiesterase-5 (PDE5) degrades cGMP and inhibits nitric oxide-mediated, cGMP-dependent vasorelaxation. We previously reported that ventilation with 100% O2 increased PDE5 activity in pulmonary arteries (PAs) of pulmonary hypertension lambs (PPHN) more than in control lambs. In the present study, PA smooth muscle cells (PASMCs) from PPHN lambs had increased basal PDE5 activity, decreased cGMP-responsiveness to NO, and increased mitochondrial matrix oxidant stress compared to control PASMC. Hyperoxia (24 h) increased PDE5 activity and mitochondrial matrix oxidant stress above baseline to a similar degree in PPHN and control PASMC. Mitochondrially targeted catalase decreased PDE5 activity at baseline and after hyperoxia in PPHN PASMC. Similarly, catalase treatment of PPHN lambs ventilated with 100% O2 decreased PDE5 activity and increased cGMP in PA. We conclude that baseline PDE5 activity and oxidative stress is increased in PPHN PASMC, and scavenging H2O2 is sufficient to block oxidant-mediated increases in PDE5 activity in PPHN. |
| Databáze: | OpenAIRE |
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