English (United Kingdom)

https://curated-unify.zendy.io/wp-json/zendy-region/v1/featured_content/oa?rat=en

https://curated-unify.zendy.io/wp-json/zendy-region/v1/highlighted_journal/

Global: Zendy Plus annual

Presents the access of premium content as premium feature

Premium Content

Presents the keyphrase highlighting as premium feature

Keyphrase Highlighting

Presents the summarisation as premium feature

Summarisation

Insights

Presents the pdf analysis as premium feature

PDF Analysis

Presents the zaia usage as premium feature

ZAIA

Global: Zendy Tools annual

Global: Zendy Free Plan

Global: Zendy Tools monthly

Global: Zendy Plus monthly

Increased levels of inflammatory cytokines contribute to the pathophysiology of pulmonary hypertension. Prostacyclin (PGI2 ) analogues, which relax pulmonary vessels mainly through cAMP elevation, have a major therapeutic role. In this study, we show that prolonged incubation with bradykinin (BK), interleukin-1β (IL-1β), and transforming growth factor-β1 (TGF-β1 ) markedly impairs cAMP accumulation in human pulmonary artery smooth muscle cells in response to short-term incubation with prostaglandin E2 (PGE2 ) and the PGI2 analogues iloprost and carbaprostacyclin. A similar reduction in cAMP accumulation in response to a direct adenylyl cyclase activator, forskolin, suggested that the effect was attributable to downregulation of adenylyl cyclase. Reverse transcriptase–polymerase chain reaction studies showed downregulation of adenylyl cyclase isoforms 1, 2, and 4. The effect of IL-1β, BK, and TGF-β1 on cAMP levels was abrogated by the selective COX-2 inhibitor NS398. Furthermore, it was mimicked by prolonged incubation with the COX-2 product PGE2 and PGI2 analogues or the COX substrate arachidonic acid, suggesting that it was mediated by endogenous prostanoids produced by COX-2. Consistent with this, IL-1β, BK, and TGF-β1 all induced COX-2 and PGE2 release. These results show that BK, IL-1β, and TGF-β1 downregulate adenylyl cyclase in human pulmonary artery smooth muscle cells via COX-2 induction and prostanoid release. This suggests a novel mechanism whereby mediators and cytokines produced in pulmonary hypertension may impair the therapeutic effects of prostacyclin analogues such as iloprost and carbaprostacyclin.

circulation research

Interleukin-1β, Transforming Growth Factor-β<sub>1</sub>, and Bradykinin Attenuate Cyclic AMP Production by Human Pulmonary Artery Smooth Muscle Cells in Response to Prostacyclin Analogues and Prostaglandin E<sub>2</sub>by Cyclooxygenase-2 Induction and Downregulation of Adenylyl Cyclase Isoforms 1, 2, and 4

Interleukin-1β, Transforming Growth Factor-β1, and Bradykinin Attenuate Cyclic AMP Production by Human Pulmonary Artery Smooth Muscle Cells in Response to Prostacyclin Analogues and Prostaglandin E2by Cyclooxygenase-2 Induction and Downregulation of Adenylyl Cyclase Isoforms 1, 2, and 4

Interleukin-1β, Transforming Growth Factor-β₁, and Bradykinin Attenuate Cyclic AMP Production by Human Pulmonary Artery Smooth Muscle Cells in Response to Prostacyclin Analogues and Prostaglandin E₂by Cyclooxygenase-2 Induction and Downregulation of Adenylyl Cyclase Isoforms 1, 2, and 4