Nitric Oxide-cGMP Pathway Modulation in an Experimental Model of Hypoxic Pulmonary Hypertension.

Details

Serval ID
serval:BIB_0F1AC8791D65
Type
Article: article from journal or magazin.
Collection
Publications
Institution
Title
Nitric Oxide-cGMP Pathway Modulation in an Experimental Model of Hypoxic Pulmonary Hypertension.
Journal
Journal of cardiovascular pharmacology and therapeutics
Author(s)
Reinero M., Beghetti M., Tozzi P., Segesser LKV, Samaja M., Milano G.
ISSN
1940-4034 (Electronic)
ISSN-L
1074-2484
Publication state
In Press
Peer-reviewed
Oui
Language
english
Notes
Publication types: Journal Article
Publication Status: aheadofprint
Abstract
Manipulation of nitric oxide (NO) may enable control of progression and treatment of pulmonary hypertension (PH). Several approaches may modulate the NO-cGMP pathway in vivo. Here, we investigate the effectiveness of 3 modulatory sites: (i) the amount of l-arginine; (ii) the size of plasma NO stores that stimulate soluble guanylate cyclase; (iii) the conversion of cGMP into inactive 5'-GMP, with respect to hypoxia, to test the effectiveness of the treatments with respect to hypoxia-induced PH. Male rats (n = 80; 10/group) maintained in normoxic (21% O <sub>2</sub> ) or hypoxic chambers (10% O <sub>2</sub> ) for 14 days were subdivided in 4 sub-groups: placebo, l-arginine (20 mg/ml), the NO donor molsidomine (15 mg/kg in drinking water), and phoshodiesterase-5 inhibitor sildenafil (1.4 mg/kg in 0.3 ml saline, i.p.). Hypoxia depressed homeostasis and increased erythropoiesis, heart and right ventricle hypertrophy, myocardial fibrosis and apoptosis inducing pulmonary remodeling. Stimulating anyone of the 3 mechanisms that enhance the NO-cGMP pathway helped rescuing the functional and morphological changes in the cardiopulmonary system leading to improvement, sometimes normalization, of the pressures. None of the treatments affected the observed parameters in normoxia. Thus, the 3 modulatory sites are essentially similar in enhancing the NO-cGMP pathway, thereby attenuating the hypoxia-related effects that lead to pulmonary hypertension.
Keywords
NO-cGMP pathway, NO-donors, PDE5 inhibitors, hypoxia, l-arginine, pulmonary hypertension
Pubmed
Web of science
Open Access
Yes
Create date
21/05/2021 17:10
Last modification date
29/05/2021 6:32
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