Investigating myoendothelial signalling mechanisms in resistance arteries
<p>The regulation of resistance artery tone is a key determinant of blood pressure and tissue perfusion. It is well-established that endothelial cells (ECs) cause vasodilation by producing nitric oxide (NO) and endothelium-dependent hyperpolarization (EDH) in response to circulating vasoactive...
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| Format: | Thesis |
| Language: | English |
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2019
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| _version_ | 1797093820327788544 |
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| author | Lemmey, H |
| author2 | Dora, K |
| author_facet | Dora, K Lemmey, H |
| author_sort | Lemmey, H |
| collection | OXFORD |
| description | <p>The regulation of resistance artery tone is a key determinant of blood pressure and tissue perfusion. It is well-established that endothelial cells (ECs) cause vasodilation by producing nitric oxide (NO) and endothelium-dependent hyperpolarization (EDH) in response to circulating vasoactive factors and flow. However, recent evidence has elucidated an intrinsic signalling mechanism, termed myoendothelial feedback, whereby ECs are activated during contraction independently of direct stimulation. The investigations presented in this thesis aimed to characterise myoendothelial feedback in isolated resistance arteries under isobaric and isometric conditions using pressure and wire myography, respectively. Most significantly, the profile of myoendothelial feedback differed between the two experimental approaches. In arteries studied isometrically, inhibition of NO and EDH production increased sensitivity to contractile agonists. On the other hand, blockade of endothelium-dependent vasodilation in pressurised arteries had no effect on submaximal contraction during sympathetic perivascular nerve stimulation and only augmented the maximum contractile response to agonists. Furthermore, arteries in the pressure myograph were less sensitive to NO, which may reflect pressure-induced smooth muscle Ca2+ sensitization and an abrogated influence of EC-dependent signalling. Additionally, a role for transient receptor potential cation channel subfamily V member 4 (TRPV4) in myoendothelial feedback was probed. However, while promising, this line of investigation was complicated by the observation that TRPV4 inhibition attenuated depolarization- dependent and -independent contraction, as well as endothelium-dependent vasodilation. The findings reported here have significant implications for the study of isolated resistance artery physiology and identify novel avenues of future research.</p> |
| first_indexed | 2024-03-07T04:05:41Z |
| format | Thesis |
| id | oxford-uuid:c6105414-da49-415d-8808-11a367ae9b78 |
| institution | University of Oxford |
| language | English |
| last_indexed | 2024-03-07T04:05:41Z |
| publishDate | 2019 |
| record_format | dspace |
| spelling | oxford-uuid:c6105414-da49-415d-8808-11a367ae9b782022-03-27T06:35:32ZInvestigating myoendothelial signalling mechanisms in resistance arteriesThesishttp://purl.org/coar/resource_type/c_db06uuid:c6105414-da49-415d-8808-11a367ae9b78Vascular physiologyVascular pharmacologyEnglishORA Deposit2019Lemmey, HDora, KGarland, C<p>The regulation of resistance artery tone is a key determinant of blood pressure and tissue perfusion. It is well-established that endothelial cells (ECs) cause vasodilation by producing nitric oxide (NO) and endothelium-dependent hyperpolarization (EDH) in response to circulating vasoactive factors and flow. However, recent evidence has elucidated an intrinsic signalling mechanism, termed myoendothelial feedback, whereby ECs are activated during contraction independently of direct stimulation. The investigations presented in this thesis aimed to characterise myoendothelial feedback in isolated resistance arteries under isobaric and isometric conditions using pressure and wire myography, respectively. Most significantly, the profile of myoendothelial feedback differed between the two experimental approaches. In arteries studied isometrically, inhibition of NO and EDH production increased sensitivity to contractile agonists. On the other hand, blockade of endothelium-dependent vasodilation in pressurised arteries had no effect on submaximal contraction during sympathetic perivascular nerve stimulation and only augmented the maximum contractile response to agonists. Furthermore, arteries in the pressure myograph were less sensitive to NO, which may reflect pressure-induced smooth muscle Ca2+ sensitization and an abrogated influence of EC-dependent signalling. Additionally, a role for transient receptor potential cation channel subfamily V member 4 (TRPV4) in myoendothelial feedback was probed. However, while promising, this line of investigation was complicated by the observation that TRPV4 inhibition attenuated depolarization- dependent and -independent contraction, as well as endothelium-dependent vasodilation. The findings reported here have significant implications for the study of isolated resistance artery physiology and identify novel avenues of future research.</p> |
| spellingShingle | Vascular physiology Vascular pharmacology Lemmey, H Investigating myoendothelial signalling mechanisms in resistance arteries |
| title | Investigating myoendothelial signalling mechanisms in resistance arteries |
| title_full | Investigating myoendothelial signalling mechanisms in resistance arteries |
| title_fullStr | Investigating myoendothelial signalling mechanisms in resistance arteries |
| title_full_unstemmed | Investigating myoendothelial signalling mechanisms in resistance arteries |
| title_short | Investigating myoendothelial signalling mechanisms in resistance arteries |
| title_sort | investigating myoendothelial signalling mechanisms in resistance arteries |
| topic | Vascular physiology Vascular pharmacology |
| work_keys_str_mv | AT lemmeyh investigatingmyoendothelialsignallingmechanismsinresistancearteries |