Original Research: Role of phosphodiesterases in modulation of BK channels in hypertensive pulmonary arterial smooth muscle
BK Ca channels regulate pulmonary arterial pressure, and protein kinase C (PKC) inhibits BK Ca channels, but little is known about PKC-mediated modulation of BK Ca channel activity in pulmonary arterial smooth muscle. Studies were carried out to determine mechanisms of PKC modulation of BK Ca channe...
| Main Authors: | , , |
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| Format: | Article |
| Language: | English |
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SAGE Publishing
2008-06-01
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| Series: | Therapeutic Advances in Respiratory Disease |
| Online Access: | https://doi.org/10.1177/1753465808091327 |
| _version_ | 1818204679264272384 |
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| author | Shu Zhu Richard E. White Scott A. Barman |
| author_facet | Shu Zhu Richard E. White Scott A. Barman |
| author_sort | Shu Zhu |
| collection | DOAJ |
| description | BK Ca channels regulate pulmonary arterial pressure, and protein kinase C (PKC) inhibits BK Ca channels, but little is known about PKC-mediated modulation of BK Ca channel activity in pulmonary arterial smooth muscle. Studies were carried out to determine mechanisms of PKC modulation of BK Ca channel activity in pulmonary arterial smooth muscle cells (PASMC) of the fawn-hooded rat (FHR), an animal model of pulmonary hypertension. Forskolin opened BK Ca channels in FHR PASMC, which was blocked by PKC activation, and reversed by the phosphodiesterase (PDE) inhibitors IBMX, milrinone, and zaprinast. PDE inhibition also blocked the vasoconstrictor response to PKC activation in FHR pulmonary arteries. These results indicate that PKC inhibits cAMP-induced activation of BK Ca channels and causes pulmonary vasoconstriction in hypertensive pulmonary arterial smooth muscle via PDE, which further suggests PDE inhibitors for treatment of pulmonary hypertension. |
| first_indexed | 2024-12-12T03:45:04Z |
| format | Article |
| id | doaj.art-61148d97fae443f8b75cbbb8312d2a3e |
| institution | Directory Open Access Journal |
| issn | 1753-4658 |
| language | English |
| last_indexed | 2024-12-12T03:45:04Z |
| publishDate | 2008-06-01 |
| publisher | SAGE Publishing |
| record_format | Article |
| series | Therapeutic Advances in Respiratory Disease |
| spelling | doaj.art-61148d97fae443f8b75cbbb8312d2a3e2022-12-22T00:39:34ZengSAGE PublishingTherapeutic Advances in Respiratory Disease1753-46582008-06-01210.1177/1753465808091327Original Research: Role of phosphodiesterases in modulation of BK channels in hypertensive pulmonary arterial smooth muscle Shu ZhuRichard E. WhiteScott A. BarmanBK Ca channels regulate pulmonary arterial pressure, and protein kinase C (PKC) inhibits BK Ca channels, but little is known about PKC-mediated modulation of BK Ca channel activity in pulmonary arterial smooth muscle. Studies were carried out to determine mechanisms of PKC modulation of BK Ca channel activity in pulmonary arterial smooth muscle cells (PASMC) of the fawn-hooded rat (FHR), an animal model of pulmonary hypertension. Forskolin opened BK Ca channels in FHR PASMC, which was blocked by PKC activation, and reversed by the phosphodiesterase (PDE) inhibitors IBMX, milrinone, and zaprinast. PDE inhibition also blocked the vasoconstrictor response to PKC activation in FHR pulmonary arteries. These results indicate that PKC inhibits cAMP-induced activation of BK Ca channels and causes pulmonary vasoconstriction in hypertensive pulmonary arterial smooth muscle via PDE, which further suggests PDE inhibitors for treatment of pulmonary hypertension.https://doi.org/10.1177/1753465808091327 |
| spellingShingle | Shu Zhu Richard E. White Scott A. Barman Original Research: Role of phosphodiesterases in modulation of BK channels in hypertensive pulmonary arterial smooth muscle Therapeutic Advances in Respiratory Disease |
| title | Original Research: Role of phosphodiesterases in modulation of BK channels in hypertensive pulmonary arterial smooth muscle |
| title_full | Original Research: Role of phosphodiesterases in modulation of BK channels in hypertensive pulmonary arterial smooth muscle |
| title_fullStr | Original Research: Role of phosphodiesterases in modulation of BK channels in hypertensive pulmonary arterial smooth muscle |
| title_full_unstemmed | Original Research: Role of phosphodiesterases in modulation of BK channels in hypertensive pulmonary arterial smooth muscle |
| title_short | Original Research: Role of phosphodiesterases in modulation of BK channels in hypertensive pulmonary arterial smooth muscle |
| title_sort | original research role of phosphodiesterases in modulation of bk channels in hypertensive pulmonary arterial smooth muscle |
| url | https://doi.org/10.1177/1753465808091327 |
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