Hyperoxia‐induced airflow restriction and Renin‐Angiotensin System expression in a bronchopulmonary dysplasia mouse model
Abstract Mechanisms underlying hyperoxia‐induced airflow restriction in the pediatric lung disease Bronchopulmonary dysplasia (BPD) are unclear. We hypothesized a role for Renin‐Angiotensin System (RAS) activity in BPD. RAS is comprised of a pro‐developmental pathway consisting of angiotensin conver...
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| Format: | Article |
| Language: | English |
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Wiley
2024-01-01
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| Series: | Physiological Reports |
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| Online Access: | https://doi.org/10.14814/phy2.15895 |
| _version_ | 1827378885679906816 |
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| author | Jasmine Dowell Zachary Bice Ke Yan Girija G. Konduri |
| author_facet | Jasmine Dowell Zachary Bice Ke Yan Girija G. Konduri |
| author_sort | Jasmine Dowell |
| collection | DOAJ |
| description | Abstract Mechanisms underlying hyperoxia‐induced airflow restriction in the pediatric lung disease Bronchopulmonary dysplasia (BPD) are unclear. We hypothesized a role for Renin‐Angiotensin System (RAS) activity in BPD. RAS is comprised of a pro‐developmental pathway consisting of angiotensin converting enzyme‐2 (ACE2) and angiotensin II receptor type 2 (AT2), and a pro‐fibrotic pathway mediated by angiotensin II receptor type 1 (AT1). We investigated associations between neonatal hyperoxia, airflow restriction, and RAS activity in a BPD mouse model. C57 mouse pups were randomized to normoxic (FiO2 = 0.21) or hyperoxic (FiO2 = 0.75) conditions for 15 days (P1–P15). At P15, P20, and P30, we measured airflow restriction using plethysmography and ACE2, AT1, and AT2 mRNA and protein expression via polymerase chain reaction and Western Blot. Hyperoxia increased airflow restriction P15 and P20, decreased ACE2 and AT2 mRNA, decreased AT2 protein, and increased AT1 protein expression. ACE2 mRNA and protein remained suppressed at P20. By P30, airflow restriction and RAS expression did not differ between groups. Hyperoxia caused high airflow restriction, increased pulmonary expression of the pro‐fibrotic RAS pathway, and decreased expression of the pro‐developmental in our BPD mouse model. These associated findings may point to a causal role for RAS in hyperoxia‐induced airflow restriction. |
| first_indexed | 2024-03-08T13:04:22Z |
| format | Article |
| id | doaj.art-86373901d64e4430b5042dfb6b198bc1 |
| institution | Directory Open Access Journal |
| issn | 2051-817X |
| language | English |
| last_indexed | 2024-03-08T13:04:22Z |
| publishDate | 2024-01-01 |
| publisher | Wiley |
| record_format | Article |
| series | Physiological Reports |
| spelling | doaj.art-86373901d64e4430b5042dfb6b198bc12024-01-19T02:01:44ZengWileyPhysiological Reports2051-817X2024-01-01121n/an/a10.14814/phy2.15895Hyperoxia‐induced airflow restriction and Renin‐Angiotensin System expression in a bronchopulmonary dysplasia mouse modelJasmine Dowell0Zachary Bice1Ke Yan2Girija G. Konduri3Medical College of Wisconsin Milwaukee Wisconsin USAMedical College of Wisconsin Milwaukee Wisconsin USAMedical College of Wisconsin Milwaukee Wisconsin USAMedical College of Wisconsin Milwaukee Wisconsin USAAbstract Mechanisms underlying hyperoxia‐induced airflow restriction in the pediatric lung disease Bronchopulmonary dysplasia (BPD) are unclear. We hypothesized a role for Renin‐Angiotensin System (RAS) activity in BPD. RAS is comprised of a pro‐developmental pathway consisting of angiotensin converting enzyme‐2 (ACE2) and angiotensin II receptor type 2 (AT2), and a pro‐fibrotic pathway mediated by angiotensin II receptor type 1 (AT1). We investigated associations between neonatal hyperoxia, airflow restriction, and RAS activity in a BPD mouse model. C57 mouse pups were randomized to normoxic (FiO2 = 0.21) or hyperoxic (FiO2 = 0.75) conditions for 15 days (P1–P15). At P15, P20, and P30, we measured airflow restriction using plethysmography and ACE2, AT1, and AT2 mRNA and protein expression via polymerase chain reaction and Western Blot. Hyperoxia increased airflow restriction P15 and P20, decreased ACE2 and AT2 mRNA, decreased AT2 protein, and increased AT1 protein expression. ACE2 mRNA and protein remained suppressed at P20. By P30, airflow restriction and RAS expression did not differ between groups. Hyperoxia caused high airflow restriction, increased pulmonary expression of the pro‐fibrotic RAS pathway, and decreased expression of the pro‐developmental in our BPD mouse model. These associated findings may point to a causal role for RAS in hyperoxia‐induced airflow restriction.https://doi.org/10.14814/phy2.15895airflow restrictionbronchopulmonary dysplasiahyperoxiamouse modelpediatric lung diseaseRenin‐Angiotensin System |
| spellingShingle | Jasmine Dowell Zachary Bice Ke Yan Girija G. Konduri Hyperoxia‐induced airflow restriction and Renin‐Angiotensin System expression in a bronchopulmonary dysplasia mouse model Physiological Reports airflow restriction bronchopulmonary dysplasia hyperoxia mouse model pediatric lung disease Renin‐Angiotensin System |
| title | Hyperoxia‐induced airflow restriction and Renin‐Angiotensin System expression in a bronchopulmonary dysplasia mouse model |
| title_full | Hyperoxia‐induced airflow restriction and Renin‐Angiotensin System expression in a bronchopulmonary dysplasia mouse model |
| title_fullStr | Hyperoxia‐induced airflow restriction and Renin‐Angiotensin System expression in a bronchopulmonary dysplasia mouse model |
| title_full_unstemmed | Hyperoxia‐induced airflow restriction and Renin‐Angiotensin System expression in a bronchopulmonary dysplasia mouse model |
| title_short | Hyperoxia‐induced airflow restriction and Renin‐Angiotensin System expression in a bronchopulmonary dysplasia mouse model |
| title_sort | hyperoxia induced airflow restriction and renin angiotensin system expression in a bronchopulmonary dysplasia mouse model |
| topic | airflow restriction bronchopulmonary dysplasia hyperoxia mouse model pediatric lung disease Renin‐Angiotensin System |
| url | https://doi.org/10.14814/phy2.15895 |
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