The levosimendan metabolite OR-1896 elicits vasodilation by activating the K(ATP) and BK(Ca) channels in rat isolated arterioles.
1. We characterized the vasoactive effects of OR-1896, the long-lived metabolite of the inodilator levosimendan, in coronary and skeletal muscle microvessels. 2. The effect of OR-1896 on isolated, pressurized (80 mmHg) rat coronary and gracilis muscle arteriole (approximately 150 microm) diameters w...
| Main Authors: | , , , , |
|---|---|
| Format: | Journal article |
| Language: | English |
| Published: |
2006
|
| _version_ | 1797087146687856640 |
|---|---|
| author | Erdei, N Papp, Z Pollesello, P Edes, I Bagi, Z |
| author_facet | Erdei, N Papp, Z Pollesello, P Edes, I Bagi, Z |
| author_sort | Erdei, N |
| collection | OXFORD |
| description | 1. We characterized the vasoactive effects of OR-1896, the long-lived metabolite of the inodilator levosimendan, in coronary and skeletal muscle microvessels. 2. The effect of OR-1896 on isolated, pressurized (80 mmHg) rat coronary and gracilis muscle arteriole (approximately 150 microm) diameters was investigated by videomicroscopy. 3. OR-1896 elicited concentration-dependent (1 nM-10 microM) dilations in coronary (maximal dilation: 66+/-6%, relative to that in Ca2+-free solutions; pD2: 7.16+/-0.42) and gracilis muscle arterioles (maximal dilation: 73+/-4%; pD2: 6.71+/-0.42), these dilations proving comparable to those induced by levosimendan (1 nM-10 microM) in coronary (maximal dilation: 83+/-6%; pD2: 7.06+/-0.14) and gracilis muscle arterioles (maximal dilation: 73+/-12%; pD2: 7.05+/-0.1). 4. The maximal dilations in response to OR-1896 were significantly (P<0.05) attenuated by the nonselective K+ channel inhibitor tetraethylammonium (1 mM) in coronary (to 34+/-9%) and gracilis muscle arterioles (to 28+/-6%). 5. Glibenclamide (5 or 10 microM), a selective ATP-sensitive K+ channel (KATP) blocker, elicited a greater reduction of OR-1896-induced dilations in skeletal muscle arterioles than in coronary microvessels. 6. Conversely, the selective inhibition of the large conductance Ca2+-activated K+ channels (BK(Ca)) with iberiotoxin (100 nM) significantly reduced the OR-1896-induced maximal dilation in coronary arterioles (to 21+/-6%), but was ineffective in skeletal muscle arterioles (72+/-8%). 7. Accordingly, OR-1896 elicits a substantial vasodilation in coronary and skeletal muscle arterioles, by activating primarily BK(Ca) and K(ATP) channels, respectively, and it is suggested that OR-1896 contributes to the long-term hemodynamic effects of levosimendan. |
| first_indexed | 2024-03-07T02:31:52Z |
| format | Journal article |
| id | oxford-uuid:a7818b54-e558-4d28-8730-f2fa0b5f474c |
| institution | University of Oxford |
| language | English |
| last_indexed | 2024-03-07T02:31:52Z |
| publishDate | 2006 |
| record_format | dspace |
| spelling | oxford-uuid:a7818b54-e558-4d28-8730-f2fa0b5f474c2022-03-27T02:55:06ZThe levosimendan metabolite OR-1896 elicits vasodilation by activating the K(ATP) and BK(Ca) channels in rat isolated arterioles.Journal articlehttp://purl.org/coar/resource_type/c_dcae04bcuuid:a7818b54-e558-4d28-8730-f2fa0b5f474cEnglishSymplectic Elements at Oxford2006Erdei, NPapp, ZPollesello, PEdes, IBagi, Z1. We characterized the vasoactive effects of OR-1896, the long-lived metabolite of the inodilator levosimendan, in coronary and skeletal muscle microvessels. 2. The effect of OR-1896 on isolated, pressurized (80 mmHg) rat coronary and gracilis muscle arteriole (approximately 150 microm) diameters was investigated by videomicroscopy. 3. OR-1896 elicited concentration-dependent (1 nM-10 microM) dilations in coronary (maximal dilation: 66+/-6%, relative to that in Ca2+-free solutions; pD2: 7.16+/-0.42) and gracilis muscle arterioles (maximal dilation: 73+/-4%; pD2: 6.71+/-0.42), these dilations proving comparable to those induced by levosimendan (1 nM-10 microM) in coronary (maximal dilation: 83+/-6%; pD2: 7.06+/-0.14) and gracilis muscle arterioles (maximal dilation: 73+/-12%; pD2: 7.05+/-0.1). 4. The maximal dilations in response to OR-1896 were significantly (P<0.05) attenuated by the nonselective K+ channel inhibitor tetraethylammonium (1 mM) in coronary (to 34+/-9%) and gracilis muscle arterioles (to 28+/-6%). 5. Glibenclamide (5 or 10 microM), a selective ATP-sensitive K+ channel (KATP) blocker, elicited a greater reduction of OR-1896-induced dilations in skeletal muscle arterioles than in coronary microvessels. 6. Conversely, the selective inhibition of the large conductance Ca2+-activated K+ channels (BK(Ca)) with iberiotoxin (100 nM) significantly reduced the OR-1896-induced maximal dilation in coronary arterioles (to 21+/-6%), but was ineffective in skeletal muscle arterioles (72+/-8%). 7. Accordingly, OR-1896 elicits a substantial vasodilation in coronary and skeletal muscle arterioles, by activating primarily BK(Ca) and K(ATP) channels, respectively, and it is suggested that OR-1896 contributes to the long-term hemodynamic effects of levosimendan. |
| spellingShingle | Erdei, N Papp, Z Pollesello, P Edes, I Bagi, Z The levosimendan metabolite OR-1896 elicits vasodilation by activating the K(ATP) and BK(Ca) channels in rat isolated arterioles. |
| title | The levosimendan metabolite OR-1896 elicits vasodilation by activating the K(ATP) and BK(Ca) channels in rat isolated arterioles. |
| title_full | The levosimendan metabolite OR-1896 elicits vasodilation by activating the K(ATP) and BK(Ca) channels in rat isolated arterioles. |
| title_fullStr | The levosimendan metabolite OR-1896 elicits vasodilation by activating the K(ATP) and BK(Ca) channels in rat isolated arterioles. |
| title_full_unstemmed | The levosimendan metabolite OR-1896 elicits vasodilation by activating the K(ATP) and BK(Ca) channels in rat isolated arterioles. |
| title_short | The levosimendan metabolite OR-1896 elicits vasodilation by activating the K(ATP) and BK(Ca) channels in rat isolated arterioles. |
| title_sort | levosimendan metabolite or 1896 elicits vasodilation by activating the k atp and bk ca channels in rat isolated arterioles |
| work_keys_str_mv | AT erdein thelevosimendanmetaboliteor1896elicitsvasodilationbyactivatingthekatpandbkcachannelsinratisolatedarterioles AT pappz thelevosimendanmetaboliteor1896elicitsvasodilationbyactivatingthekatpandbkcachannelsinratisolatedarterioles AT pollesellop thelevosimendanmetaboliteor1896elicitsvasodilationbyactivatingthekatpandbkcachannelsinratisolatedarterioles AT edesi thelevosimendanmetaboliteor1896elicitsvasodilationbyactivatingthekatpandbkcachannelsinratisolatedarterioles AT bagiz thelevosimendanmetaboliteor1896elicitsvasodilationbyactivatingthekatpandbkcachannelsinratisolatedarterioles AT erdein levosimendanmetaboliteor1896elicitsvasodilationbyactivatingthekatpandbkcachannelsinratisolatedarterioles AT pappz levosimendanmetaboliteor1896elicitsvasodilationbyactivatingthekatpandbkcachannelsinratisolatedarterioles AT pollesellop levosimendanmetaboliteor1896elicitsvasodilationbyactivatingthekatpandbkcachannelsinratisolatedarterioles AT edesi levosimendanmetaboliteor1896elicitsvasodilationbyactivatingthekatpandbkcachannelsinratisolatedarterioles AT bagiz levosimendanmetaboliteor1896elicitsvasodilationbyactivatingthekatpandbkcachannelsinratisolatedarterioles |