Pannexin 1 (Panx1) deletion affects the mechanisms of endothelium-dependent relaxation in murine basilar artery

Kiryukhina, O.; Tarasova, O.

Авторы: Kiryukhina O., Tarasova O.
Журнал: Acta Physiologica
Том: 219
Номер: Supplement S710
Год издания: 2017
Издательство: Blackwell Publishing Inc.
Местоположение издательства: United Kingdom
Первая страница: 37
Последняя страница: 37
DOI: 10.1111/apha.12841
Аннотация: Introduction: Panx1 was shown to facilitate endothelium-dependent vasorelaxation in peripheral arteries (Gaynullina et al. FEBS Lett 2015; 589 1164-70). Along with that, global Panx1 knockout (KO) protected brain from ischemic injury (Cisneros-Mejorado et al. J Cereb Blood Flow Metab 2015; 35 843-50), which may be associated with Panx1 role in cerebral vasculature. Notably, the role of Panx1 in cerebral arteries is unknown and we addressed it using a model of global Panx1 KO in mice. Materials and Methods: Experiments were performed on 2–3 months old male Panx1 KO and C57BL/6 (WT) mice. The segments of basilar artery were mounted in wire myograph (DMT). Endothelial pathways were dissected using NO-synthase inhibitor L-NNA, cyclooxygenase inhibitor indomethacin (Indo) and the combination of IKCa/SKCa channels blockers (TRAM34 + UCL1684). ACh-induced relaxation was studied after U46619-induced precontraction. Results: Responses to ACh differed in KO and WT in amplitude (KO>WT) and underlying mechanisms. In WT the response was equally blocked by either L-NNA or the combination of Indo+TRAM34+UCL1684, i.e. NO and EDHF components were additive and each of them was about half of the total response. However, in KO the response to ACh was not affected by either L-NNA or the combination of Indo+TRAM34+UCL1684, but eliminated by the mixture of all four blockers. Conclusion: In basilar arteries of Panx1-KO mice the blockade of NO-pathway is accompanied by strong augmentation of EDHF-pathway and vice versa. Such redistribution of endothelium-derived pathways may be a mechanism of neuroprotection after Panx1 ablation.
Добавил в систему: Тарасова Ольга Сергеевна

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