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L-arginine in combination with sildenafil potentiates the attenuation of hypoxic pulmonary hypertension in rats
H. Al-Hiti, M. Chovanec, V. Melenovský, O. Vajnerová, A. Baňasová, J. Kautzner, J. Herget
Jazyk angličtina Země Česko
Typ dokumentu časopisecké články, práce podpořená grantem
Grantová podpora
NT13358
MZ0
CEP - Centrální evidence projektů
Digitální knihovna NLK
Plný text - Článek
Zdroj
Free Medical Journals od 1998
ProQuest Central od 2005-01-01
Medline Complete (EBSCOhost) od 2006-01-01
Nursing & Allied Health Database (ProQuest) od 2005-01-01
Health & Medicine (ProQuest) od 2005-01-01
ROAD: Directory of Open Access Scholarly Resources od 1998
Odkazy
PubMed
23869884
DOI
10.33549/physiolres.932463
Knihovny.cz E-zdroje
- MeSH
- arginin aplikace a dávkování MeSH
- hypoxie komplikace farmakoterapie patofyziologie MeSH
- kombinovaná farmakoterapie MeSH
- krevní tlak účinky léků MeSH
- krysa rodu rattus MeSH
- piperaziny aplikace a dávkování MeSH
- plicní hypertenze farmakoterapie etiologie patofyziologie MeSH
- potkani Wistar MeSH
- puriny aplikace a dávkování MeSH
- sulfony aplikace a dávkování MeSH
- synergismus léků MeSH
- vazodilatancia aplikace a dávkování MeSH
- výměna plynů v plicích účinky léků MeSH
- výsledek terapie MeSH
- zvířata MeSH
- Check Tag
- krysa rodu rattus MeSH
- mužské pohlaví MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
Chronic hypoxia induces an increased production of nitric oxide (NO) in pulmonary prealveolar arterioles. Bioavailability of the NO in the pulmonary vessels correlates with concentration of L-arginine as well as activity of phosphodiesterase-5 enzyme (PDE-5). We tested a hypothesis whether a combination of L-arginine and PDE-5 inhibitor sildenafil has an additive effect in reduction of the hypoxic pulmonary hypertension (HPH) in rats. Animals were exposed to chronic normobaric hypoxia for 3 weeks. In the AH group, rats were administered L-arginine during chronic hypoxic exposure. In the SH group, rats were administered sildenafil during chronic hypoxic exposure. In the SAH group, rats were treated by the combination of L-arginine as well as sildenafil during exposure to chronic hypoxia. Mean PAP, structural remodeling of peripheral pulmonary arterioles (%DL) and RV/LV+S ratio was significantly decreased in the SAH group compared to hypoxic controls even decreased compared to the AH and the SH groups in first two measured parameters. Plasmatic concentration of cGMP and NOx were significantly lower in the SAH group compared to hypoxic controls. We demonstrate that NO synthase substrate L-arginine and phosphodiesterase-5 inhibitor sildenafil administered in combination are more potent in attenuation of the HPH compared to a treatment by substances given alone.
Department of Cardiology Institute for Clinical and Experimental Medicine Prague
Department of Cardiology Na Homolce Hospital Prague
Department of Pathophysiology 2nd Medical School Charles University Prague Czech Republic
Department of Physiology 2nd Medical School Charles University Prague Czech Republic
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- $a Chronic hypoxia induces an increased production of nitric oxide (NO) in pulmonary prealveolar arterioles. Bioavailability of the NO in the pulmonary vessels correlates with concentration of L-arginine as well as activity of phosphodiesterase-5 enzyme (PDE-5). We tested a hypothesis whether a combination of L-arginine and PDE-5 inhibitor sildenafil has an additive effect in reduction of the hypoxic pulmonary hypertension (HPH) in rats. Animals were exposed to chronic normobaric hypoxia for 3 weeks. In the AH group, rats were administered L-arginine during chronic hypoxic exposure. In the SH group, rats were administered sildenafil during chronic hypoxic exposure. In the SAH group, rats were treated by the combination of L-arginine as well as sildenafil during exposure to chronic hypoxia. Mean PAP, structural remodeling of peripheral pulmonary arterioles (%DL) and RV/LV+S ratio was significantly decreased in the SAH group compared to hypoxic controls even decreased compared to the AH and the SH groups in first two measured parameters. Plasmatic concentration of cGMP and NOx were significantly lower in the SAH group compared to hypoxic controls. We demonstrate that NO synthase substrate L-arginine and phosphodiesterase-5 inhibitor sildenafil administered in combination are more potent in attenuation of the HPH compared to a treatment by substances given alone.
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