Ozen, G;
Benyahia, C;
Mani, S;
Boukais, K;
Silverstein, AM;
Bayles, R;
Nelsen, AC;
... Norel, X; + view all
(2020)
Bronchodilation induced by PGE2 is impaired in Group-III pulmonary hypertension.
British Journal of Pharmacology
, 177
(1)
pp. 161-174.
10.1111/bph.14854.
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Abstract
BACKGROUND AND PURPOSE: In patients with pulmonary hypertension (PH) associated with lung disease and/or hypoxia (Group III), a reduction of pulmonary vascular tone and tissue hypoxia are considered therapeutically beneficial. Prostaglandin (PG) E2 and PGI2 induce potent relaxation of human bronchi from non-PH (control) patients via EP4 and IP receptors, respectively. However, the effects of PGE2 /PGI2 and their mimetics on human bronchi from PH-patients are unknown. Our aim was to compare the relaxant effects of several PGI2 -mimetics approved for treating PH-Group I with several PGE2 -mimetics in bronchial preparations derived from PH-Group III and control patients. EXPERIMENTAL APPROACH: Using an organ bath system, the tone of bronchial muscle was investigated in tissue from either control or PH-Group III patients. Expression of prostanoid receptors were analyzed by Western blot and real-time PCR and endogenous PGE2 , PGI2 and cAMP levels were determined by ELISA. KEY RESULTS: Maximal relaxations induced by different EP4 agonists (PGE2 , L-902688, ONO-AE1-329) were significantly decreased in human bronchi from PH-patients versus controls. In contrast, the maximal relaxations produced by PGI2 -mimetics (iloprost, treprostinil, beraprost) were similar for both groups of patients. Both EP4 and IP receptor protein and mRNA expressions were significantly lower in human bronchi from PH-patients. cAMP levels significantly correlated with PGI2 but not with PGE2 levels. CONCLUSION AND IMPLICATIONS: This study shows that PGI2 -mimetics have preserved maximal bronchodilation in PH-Group III patients. The decreased bronchodilation induced by EP4 agonists suggests that restoration of EP4 expression in airways of PH-patients with respiratory diseases could bring additional therapeutic benefit.
| Type: | Article |
|---|---|
| Title: | Bronchodilation induced by PGE2 is impaired in Group-III pulmonary hypertension |
| Location: | England |
| Open access status: | An open access version is available from UCL Discovery |
| DOI: | 10.1111/bph.14854 |
| Publisher version: | https://doi.org/10.1111/bph.14854 |
| Language: | English |
| Additional information: | This version is the author accepted manuscript. For information on re-use, please refer to the publisher’s terms and conditions. |
| Keywords: | human bronchi relaxation, human pulmonary hypertension, prostacyclin, prostaglandin E2, prostanoid receptors, respiratory diseases |
| UCL classification: | UCL UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Population Health Sciences > Institute of Cardiovascular Science UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Population Health Sciences > Institute of Cardiovascular Science > Pre-clinical and Fundamental Science |
| URI: | https://discovery-pp.ucl.ac.uk/id/eprint/10083203 |
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