Protease-activated receptor 2-mediated vasodilatation in humans in vivo: role of nitric oxide and prostanoids.
BACKGROUND: Systemic hypotension as a consequence of vascular dysfunction is a well-recognized and important feature of critical illness. Although serine protease activation has been implicated as a cause of vascular dysfunction in systemic inflammation, the mechanism is unknown. Recently, a class...
| Main Authors: | , , , , |
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| Format: | Journal article |
| Language: | English |
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2003
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| _version_ | 1826266360864309248 |
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| author | Robin, J Kharbanda, R Mclean, P Campbell, R Vallance, P |
| author_facet | Robin, J Kharbanda, R Mclean, P Campbell, R Vallance, P |
| author_sort | Robin, J |
| collection | OXFORD |
| description | BACKGROUND: Systemic hypotension as a consequence of vascular dysfunction is a well-recognized and important feature of critical illness. Although serine protease activation has been implicated as a cause of vascular dysfunction in systemic inflammation, the mechanism is unknown. Recently, a class of receptors with an entirely novel mechanism of action, protease-activated receptors (PARs), has been identified that would explain the link between protease activation and systemic hypotension. Our aim was to test the hypothesis that in vivo activation of protease-activated receptor 2 (PAR-2) in humans would mediate vasodilatation. METHODS AND RESULTS: For these first-in-human studies, an activating peptide for the human PAR-2 receptor was synthesized and administered to healthy volunteers. Using both the dorsal hand vein technique and forearm plethysmography, we studied the effects of PAR-2 activation in human blood vessels and investigated the mechanism of vasodilation. Activation of PAR-2 receptors in vivo dilated human blood vessels in a dose-dependent manner, and the effects were reduced by inhibition of both nitric oxide and prostanoid synthesis CONCLUSIONS: These findings demonstrate that serine protease activity can cause human vasodilation and provide a possible explanation of why serine protease activation in critical illness is associated with vascular dysfunction. |
| first_indexed | 2024-03-06T20:37:44Z |
| format | Journal article |
| id | oxford-uuid:333067b4-b667-4e57-a33e-a72084be5463 |
| institution | University of Oxford |
| language | English |
| last_indexed | 2024-03-06T20:37:44Z |
| publishDate | 2003 |
| record_format | dspace |
| spelling | oxford-uuid:333067b4-b667-4e57-a33e-a72084be54632022-03-26T13:18:49ZProtease-activated receptor 2-mediated vasodilatation in humans in vivo: role of nitric oxide and prostanoids.Journal articlehttp://purl.org/coar/resource_type/c_dcae04bcuuid:333067b4-b667-4e57-a33e-a72084be5463EnglishSymplectic Elements at Oxford2003Robin, JKharbanda, RMclean, PCampbell, RVallance, P BACKGROUND: Systemic hypotension as a consequence of vascular dysfunction is a well-recognized and important feature of critical illness. Although serine protease activation has been implicated as a cause of vascular dysfunction in systemic inflammation, the mechanism is unknown. Recently, a class of receptors with an entirely novel mechanism of action, protease-activated receptors (PARs), has been identified that would explain the link between protease activation and systemic hypotension. Our aim was to test the hypothesis that in vivo activation of protease-activated receptor 2 (PAR-2) in humans would mediate vasodilatation. METHODS AND RESULTS: For these first-in-human studies, an activating peptide for the human PAR-2 receptor was synthesized and administered to healthy volunteers. Using both the dorsal hand vein technique and forearm plethysmography, we studied the effects of PAR-2 activation in human blood vessels and investigated the mechanism of vasodilation. Activation of PAR-2 receptors in vivo dilated human blood vessels in a dose-dependent manner, and the effects were reduced by inhibition of both nitric oxide and prostanoid synthesis CONCLUSIONS: These findings demonstrate that serine protease activity can cause human vasodilation and provide a possible explanation of why serine protease activation in critical illness is associated with vascular dysfunction. |
| spellingShingle | Robin, J Kharbanda, R Mclean, P Campbell, R Vallance, P Protease-activated receptor 2-mediated vasodilatation in humans in vivo: role of nitric oxide and prostanoids. |
| title | Protease-activated receptor 2-mediated vasodilatation in humans in vivo: role of nitric oxide and prostanoids. |
| title_full | Protease-activated receptor 2-mediated vasodilatation in humans in vivo: role of nitric oxide and prostanoids. |
| title_fullStr | Protease-activated receptor 2-mediated vasodilatation in humans in vivo: role of nitric oxide and prostanoids. |
| title_full_unstemmed | Protease-activated receptor 2-mediated vasodilatation in humans in vivo: role of nitric oxide and prostanoids. |
| title_short | Protease-activated receptor 2-mediated vasodilatation in humans in vivo: role of nitric oxide and prostanoids. |
| title_sort | protease activated receptor 2 mediated vasodilatation in humans in vivo role of nitric oxide and prostanoids |
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