Flow-dependent regulation of rat mesenteric lymphatic vessel contractile response requires activation of endothelial TRPV4 channels
© 2023 John Wiley & Sons Ltd..
OBJECTIVES: The objective of our study is to evaluate the involvement of the transient receptor potential vanilloid 4 (TRPV4) in the alteration of lymphatic pumping in response to flow and determine the signaling pathways involved.
METHODS: We used immunofluorescence imaging and western blotting to assess TRPV4 expression in rat mesenteric lymphatic vessels. We examined inhibition of TRPV4 with HC067047, nitric oxide synthase (NOS) with L-NNA and cyclooxygenases (COXs) with indomethacin on the contractile response of pressurized lymphatic vessels to flow changes induced by a stepwise increase in pressure gradients, and the functionality of endothelial TRPV4 channels by measuring the intracellular Ca2+ response of primary lymphatic endothelial cell cultures to the selective agonist GSK1016790A.
RESULTS: TRPV4 protein was expressed in both the endothelial and the smooth muscle layer of rat mesenteric lymphatics with high endothelial expression around the valve sites. When maintained under constant transmural pressure, most lymphatic vessels displayed a decrease in contraction frequency under conditions of flow and this effect was ablated through inhibition of NOS, COX or TRPV4.
CONCLUSIONS: Our findings demonstrate a critical role for TRPV4 in the decrease in contraction frequency induced in lymphatic vessels by increases in flow rate via the production and action of nitric oxide and dilatory prostanoids.
| Medienart: |
E-Artikel |
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| Erscheinungsjahr: |
2024 |
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| Erschienen: |
2024 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:31 |
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| Enthalten in: |
Microcirculation (New York, N.Y. : 1994) - 31(2024), 2 vom: 15. Feb., Seite e12839 |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
DuToit, Jacques [VerfasserIn] |
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| Links: |
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| Themen: |
31C4KY9ESH |
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| Anmerkungen: |
Date Completed 16.02.2024 Date Revised 16.02.2024 published: Print-Electronic Citation Status MEDLINE |
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| doi: |
10.1111/micc.12839 |
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| funding: |
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| Förderinstitution / Projekttitel: |
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| PPN (Katalog-ID): |
NLM365357731 |
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| 100 | 1 | |a DuToit, Jacques |e verfasserin |4 aut | |
| 245 | 1 | 0 | |a Flow-dependent regulation of rat mesenteric lymphatic vessel contractile response requires activation of endothelial TRPV4 channels |
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| 500 | |a Date Revised 16.02.2024 | ||
| 500 | |a published: Print-Electronic | ||
| 500 | |a Citation Status MEDLINE | ||
| 520 | |a © 2023 John Wiley & Sons Ltd. | ||
| 520 | |a OBJECTIVES: The objective of our study is to evaluate the involvement of the transient receptor potential vanilloid 4 (TRPV4) in the alteration of lymphatic pumping in response to flow and determine the signaling pathways involved | ||
| 520 | |a METHODS: We used immunofluorescence imaging and western blotting to assess TRPV4 expression in rat mesenteric lymphatic vessels. We examined inhibition of TRPV4 with HC067047, nitric oxide synthase (NOS) with L-NNA and cyclooxygenases (COXs) with indomethacin on the contractile response of pressurized lymphatic vessels to flow changes induced by a stepwise increase in pressure gradients, and the functionality of endothelial TRPV4 channels by measuring the intracellular Ca2+ response of primary lymphatic endothelial cell cultures to the selective agonist GSK1016790A | ||
| 520 | |a RESULTS: TRPV4 protein was expressed in both the endothelial and the smooth muscle layer of rat mesenteric lymphatics with high endothelial expression around the valve sites. When maintained under constant transmural pressure, most lymphatic vessels displayed a decrease in contraction frequency under conditions of flow and this effect was ablated through inhibition of NOS, COX or TRPV4 | ||
| 520 | |a CONCLUSIONS: Our findings demonstrate a critical role for TRPV4 in the decrease in contraction frequency induced in lymphatic vessels by increases in flow rate via the production and action of nitric oxide and dilatory prostanoids | ||
| 650 | 4 | |a Journal Article | |
| 650 | 4 | |a TRPV4 | |
| 650 | 4 | |a lymph flow | |
| 650 | 4 | |a lymphatic pumping | |
| 650 | 4 | |a nitric oxide | |
| 650 | 4 | |a prostanoids | |
| 650 | 4 | |a thromboxane A2 | |
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| 650 | 7 | |a Transient Receptor Potential Channels |2 NLM | |
| 650 | 7 | |a Nitric Oxide |2 NLM | |
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| 700 | 1 | |a Brothers, Peter |e verfasserin |4 aut | |
| 700 | 1 | |a Stephens, Matthew |e verfasserin |4 aut | |
| 700 | 1 | |a Keane, Keith |e verfasserin |4 aut | |
| 700 | 1 | |a de Jesus, Flavia Neto |e verfasserin |4 aut | |
| 700 | 1 | |a Roizes, Simon |e verfasserin |4 aut | |
| 700 | 1 | |a von der Weid, Pierre-Yves |e verfasserin |4 aut | |
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