| Type 1 diabetes induced hyperresponsiveness to 5-HT in rat pulmonary arteries via oxidative stress and induction of cyclooxygenase-2. | |
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MedLine Citation:
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PMID: 21521772 Owner: NLM Status: Publisher |
Abstract/OtherAbstract:
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Recent epidemiological data suggest that diabetes is a risk factor for pulmonary arterial hypertension. The aim of the present study was to analyze the link between type 1 diabetes and pulmonary arterial dysfunction in rats. Male Sprague-Dawley rats were randomly divided into a control (saline) and a diabetic group (70 mg/kg streptozotocin). After 6 weeks, diabetic animals showed a downregulation of the lung bone morphogenetic protein receptor type 2 (BMPR2), upregulation of 5-HT(2A) receptors and cyclooxygenase-2 proteins as measured by Western blot analysis and increased contractile responses to 5-HT in isolated intrapulmonary arteries. The hyperresponsiveness to 5-HT was endothelium-independent and unaffected by inhibition of NO synthase but prevented by indomethacin, the selective cyclooxygenase-2 inhibitor NS398, superoxide dismutase and the NADPH oxidase inhibitor apocynin or chronic treatment with insulin. However, diabetic rats at 6 weeks did not develop elevated right ventricular pressure or pulmonary artery muscularization while a longer exposure (4 months) to diabetes induced a modest but significant increase in right ventricular systolic pressure. In conclusion, type 1 diabetes mellitus in rats induces a number of changes in lung protein expression and pulmonary vascular reactivity characteristic of clinical and experimental pulmonary arterial hypertension but insufficient to elevate pulmonary pressure. Our results further strengthen the link between diabetes and pulmonary arterial hypertension. |
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Authors:
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Jose Gustavo Lopez-Lopez; Javier Moral-Sanz; Giovanna Frazziano; Maria Jesus Gomez-Villalobos; Laura Moreno; Carmen Menendez; Jorge Flores-Hernandez; Jose Angel Lorente; Angel Cogolludo; Francisco Perez-Vizcaino |
Publication Detail:
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Type: JOURNAL ARTICLE Date: 2011-4-26 |
Journal Detail:
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Title: The Journal of pharmacology and experimental therapeutics Volume: - ISSN: 1521-0103 ISO Abbreviation: - Publication Date: 2011 Apr |
Date Detail:
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Created Date: 2011-4-27 Completed Date: - Revised Date: - |
Medline Journal Info:
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Nlm Unique ID: 0376362 Medline TA: J Pharmacol Exp Ther Country: - |
Other Details:
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Languages: ENG Pagination: - Citation Subset: - |
Affiliation:
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1 Benemerita Universidad Autonoma de Puebla; |
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From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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