Phosphodiesterase-5 Inhibition Alleviates Pulmonary Hypertension and Basal Lamina Thickening in Rats Challenged by Chronic Hypoxia.

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License: CC BY 4.0
Serval ID
serval:BIB_9ABC9DD9AB1D
Type
Article: article from journal or magazin.
Collection
Publications
Institution
Title
Phosphodiesterase-5 Inhibition Alleviates Pulmonary Hypertension and Basal Lamina Thickening in Rats Challenged by Chronic Hypoxia.
Journal
Frontiers in physiology
Author(s)
Nydegger C., Martinelli C., Di Marco F., Bulfamante G., von Segesser L., Tozzi P., Samaja M., Milano G.
ISSN
1664-042X (Print)
ISSN-L
1664-042X
Publication state
Published
Issued date
2018
Peer-reviewed
Oui
Volume
9
Pages
289
Language
english
Notes
Publication types: Journal Article
Publication Status: epublish
Abstract
javax.xml.bind.JAXBElement@6f8948ff Hypoxia represents both an outcome of cardiopulmonary diseases and a trigger for severe pulmonary complications as pulmonary hypertension. Because nitric oxide (NO) is a critical mediator in the development of pulmonary hypertension, the modulators of its downstream function may become target of pharmacological interventions aimed at alleviating the impact of this condition. Here, we investigate the effects of an early administration of phosphodiesterase-5 inhibitor in rats where pulmonary artery hypertension was induced by chronic exposure to hypoxia. javax.xml.bind.JAXBElement@162dc677 Rats were divided into three groups: normoxic control, hypoxic with no treatments (2 weeks breathing an atmosphere containing 10% oxygen), and hypoxic treated with sildenafil (1.4 mg/Kg per day in 0.3 mL i.p.). After sacrifice, hearts and lungs were removed and harvested for analyses. javax.xml.bind.JAXBElement@1961a294 Sildenafil reduced hypoxia-induced right ventricle hypertrophy without effects in lung hypertrophy, and blunted the increase in right ventricle pressure without effects on left ventricle pressure. Furthermore, the NO-producing systems (i.e., the phosphorylation of the endothelial isoforms of NO synthase that was measured in both myocardial and lung tissues), and the blood NO stores (i.e., the plasma level of nitrates and nitrites) were up-regulated by sildenafil. We did not find significant effects of sildenafil on weight and hemoglobin concentration. Morphological analysis in lung biopsies revealed that 2-week hypoxia increased the frequency of small pulmonary vessels leaving large vessels unaffected. Finally, ultrastructural analysis showed that sildenafil down-regulated the hypoxia-induced increase in the thickness of the pulmonary basal lamina. javax.xml.bind.JAXBElement@7ae1b3f8 In this model of pulmonary hypertension, sildenafil contrasts the negative effects of hypoxia on pulmonary vascular and right ventricle remodeling. This action does not only encompass the canonical vasomodulatory effect, but involves several biochemical pathways. Although the human pathological model is certainly more complex than that described here (for example, the inflammatory issue), the potential role of phosphodiesterase-5 for long-term treatment, and perhaps prevention, of pulmonary hypertension is worthy of investigation.

Keywords
endothelial NO synthase, nitric oxide, nitrites and nitrates, phosphodiesterase 5, pulmonary hypertension, pulmonary vascular remodeling, right heart failure, sildenafil
Pubmed
Web of science
Open Access
Yes
Create date
14/04/2018 8:50
Last modification date
20/08/2019 15:01
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