Possible role for K+ in endothelium-derived hyperpolarizing factor-linked dilatation in rat middle cerebral artery.
BACKGROUND AND PURPOSE: Endothelium-derived hyperpolarizing factor (EDHF) and K+ are vasodilators in the cerebral circulation. Recently, K+ has been suggested to contribute to EDHF-mediated responses in peripheral vessels. The EDHF response to the protease-activated receptor 2 ligand SLIGRL was cha...
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| Format: | Journal article |
| Language: | English |
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2005
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| _version_ | 1797053168977182720 |
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| author | McNeish, A Dora, K Garland, C |
| author_facet | McNeish, A Dora, K Garland, C |
| author_sort | McNeish, A |
| collection | OXFORD |
| description | BACKGROUND AND PURPOSE: Endothelium-derived hyperpolarizing factor (EDHF) and K+ are vasodilators in the cerebral circulation. Recently, K+ has been suggested to contribute to EDHF-mediated responses in peripheral vessels. The EDHF response to the protease-activated receptor 2 ligand SLIGRL was characterized in cerebral arteries and used to assess whether K+ contributes as an EDHF. METHODS: Rat middle cerebral arteries were mounted in either a wire or pressure myograph. Concentration-response curves to SLIGRL and K+ were constructed in the presence and absence of a variety of blocking agents. In some experiments, changes in tension and smooth muscle cell membrane potential were recorded simultaneously. RESULTS: SLIGRL (0.02 to 20 micromol/L) stimulated concentration and endothelium-dependent relaxation. In the presence of NG-nitro-L-arginine methyl ester, relaxation to SLIGRL was associated with hyperpolarization and sensitivity to a specific inhibitor of IKCa, 1-[(2-chlorophenyl)diphenylmethyl]-1H-pyrazole (1 micromol/L), reflecting activation of EDHF. Combined inhibition of KIR with Ba2+ (30 micromol/L) and Na+/K+-ATPase with ouabain (1 micromol/L) markedly attenuated the relaxation to EDHF. Raising extracellular [K+] to 15 mmol/L also stimulated smooth muscle relaxation and hyperpolarization, which was also attenuated by combined application of Ba2+ and ouabain. CONCLUSIONS: SLIGRL evokes EDHF-mediated relaxation in the rat middle cerebral artery, underpinned by hyperpolarization of the smooth muscle. The profile of blockade of EDHF-mediated hyperpolarization and relaxation supports a pivotal role for IKCa channels. Furthermore, similar inhibition of responses to EDHF and exogenous K+ with Ba2+ and ouabain suggests that K+ may contribute as an EDHF in the middle cerebral artery. |
| first_indexed | 2024-03-06T18:40:14Z |
| format | Journal article |
| id | oxford-uuid:0ca09667-a9ba-4508-baa0-f07a4c9234db |
| institution | University of Oxford |
| language | English |
| last_indexed | 2024-03-06T18:40:14Z |
| publishDate | 2005 |
| record_format | dspace |
| spelling | oxford-uuid:0ca09667-a9ba-4508-baa0-f07a4c9234db2022-03-26T09:36:00ZPossible role for K+ in endothelium-derived hyperpolarizing factor-linked dilatation in rat middle cerebral artery.Journal articlehttp://purl.org/coar/resource_type/c_dcae04bcuuid:0ca09667-a9ba-4508-baa0-f07a4c9234dbEnglishSymplectic Elements at Oxford2005McNeish, ADora, KGarland, C BACKGROUND AND PURPOSE: Endothelium-derived hyperpolarizing factor (EDHF) and K+ are vasodilators in the cerebral circulation. Recently, K+ has been suggested to contribute to EDHF-mediated responses in peripheral vessels. The EDHF response to the protease-activated receptor 2 ligand SLIGRL was characterized in cerebral arteries and used to assess whether K+ contributes as an EDHF. METHODS: Rat middle cerebral arteries were mounted in either a wire or pressure myograph. Concentration-response curves to SLIGRL and K+ were constructed in the presence and absence of a variety of blocking agents. In some experiments, changes in tension and smooth muscle cell membrane potential were recorded simultaneously. RESULTS: SLIGRL (0.02 to 20 micromol/L) stimulated concentration and endothelium-dependent relaxation. In the presence of NG-nitro-L-arginine methyl ester, relaxation to SLIGRL was associated with hyperpolarization and sensitivity to a specific inhibitor of IKCa, 1-[(2-chlorophenyl)diphenylmethyl]-1H-pyrazole (1 micromol/L), reflecting activation of EDHF. Combined inhibition of KIR with Ba2+ (30 micromol/L) and Na+/K+-ATPase with ouabain (1 micromol/L) markedly attenuated the relaxation to EDHF. Raising extracellular [K+] to 15 mmol/L also stimulated smooth muscle relaxation and hyperpolarization, which was also attenuated by combined application of Ba2+ and ouabain. CONCLUSIONS: SLIGRL evokes EDHF-mediated relaxation in the rat middle cerebral artery, underpinned by hyperpolarization of the smooth muscle. The profile of blockade of EDHF-mediated hyperpolarization and relaxation supports a pivotal role for IKCa channels. Furthermore, similar inhibition of responses to EDHF and exogenous K+ with Ba2+ and ouabain suggests that K+ may contribute as an EDHF in the middle cerebral artery. |
| spellingShingle | McNeish, A Dora, K Garland, C Possible role for K+ in endothelium-derived hyperpolarizing factor-linked dilatation in rat middle cerebral artery. |
| title | Possible role for K+ in endothelium-derived hyperpolarizing factor-linked dilatation in rat middle cerebral artery. |
| title_full | Possible role for K+ in endothelium-derived hyperpolarizing factor-linked dilatation in rat middle cerebral artery. |
| title_fullStr | Possible role for K+ in endothelium-derived hyperpolarizing factor-linked dilatation in rat middle cerebral artery. |
| title_full_unstemmed | Possible role for K+ in endothelium-derived hyperpolarizing factor-linked dilatation in rat middle cerebral artery. |
| title_short | Possible role for K+ in endothelium-derived hyperpolarizing factor-linked dilatation in rat middle cerebral artery. |
| title_sort | possible role for k in endothelium derived hyperpolarizing factor linked dilatation in rat middle cerebral artery |
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