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Transient receptor potential vanilloid‐4 channels are involved in diminished myogenic tone in brain parenchymal arterioles in response to chronic hypoperfusion in mice
Author(s) -
Chan SiuLung,
Nelson Mark T.,
Cipolla Marilyn J.
Publication year - 2019
Publication title -
acta physiologica
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.591
H-Index - 116
eISSN - 1748-1716
pISSN - 1748-1708
DOI - 10.1111/apha.13181
Subject(s) - trpv , trpv4 , transient receptor potential channel , vasodilation , chemistry , medicine , endocrinology , perfusion , agonist , capsaicin , receptor , trpv1 , anesthesia
Aim Adaptive responses of brain parenchymal arterioles ( PA s), a target for cerebral small vessel disease, to chronic cerebral hypoperfusion are largely unknown. Previous evidence suggested that transient receptor potential vanilloid 4 channels may be involved in the regulation of cerebrovascular tone. Therefore, we investigated the role of TRPV 4 in adaptations of PA s in a mouse model of chronic hypoperfusion. Methods TRPV 4 knockout ( −/− ) and wild‐type ( WT ) mice were subjected to unilateral common carotid artery occlusion ( UCCA o) for 28 days. Function and structure of PA s ipsilateral to UCCA o were studied isolated and pressurized in an arteriograph. Results Basal tone of PA s was similar between WT and TRPV 4 −/− mice (22 ± 3 vs 23 ± 5%). After UCCA o, active inner diameters of PA s from WT mice were larger than control (41 ± 2 vs 26 ± 5 μm, P < 0.05) that was due to decreased tone (8 ± 2 vs 23 ± 5%, P < 0.05), increased passive inner diameters (46 ± 3 vs 34 ± 2 μm, P < 0.05), and decreased wall‐to‐lumen ratio (0.104 ± 0.01 vs 0.137 ± 0.01, P < 0.05). However, UCCA o did not affect vasodilation to a small‐ and intermediate‐conductance calcium‐activated potassium channel agonist NS 309, the nitric oxide ( NO ) donor sodium nitroprusside, or constriction to a NO synthase inhibitor L‐ NNA . Wall thickness and distensibility in PA s from WT mice were unaffected. In TRPV 4 −/− mice, UCCA o had no effect on active inner diameters or tone and only increased passive inner diameters (53 ± 2 vs 43 ± 3 μm, P < 0.05). Conclusion Adaptive response of PA s to chronic cerebral hypoperfusion includes myogenic tone reduction and outward remodelling. TRPV 4 channels were involved in tone reduction but not outward remodelling in response to UCCA o.