King's College London British Heart Foundation Centre, Cardiovascular Division and Centre of Integrative Biomedicine, King's College London, Franklin-Wilkins Building, London SE1 9NH, UK.
Cardiovasc Res. 2010 Sep 1;87(4):760-8. doi: 10.1093/cvr/cvq118. Epub 2010 May 3.
The aim of the study is to investigate transient receptor potential ankyrin 1 (TRPA1)-induced responses in the vasculature and on blood pressure and heart rate (HR), in response to TRPA1 agonists using wild-type (WT) and TRPA1 knockout (KO) mice.
TRPA1 agonists allyl isothiocyanate and cinnamaldehyde (CA) significantly increased blood flow in the skin of anaesthetized WT, but not in TRPA1 KO mice. CA also induced TRPA1-dependent relaxation of mesenteric arteries. Intravenously injected CA induced a transient hypotensive response accompanied by decreased HR that was, depending on genotype and dose, followed by a more sustained dose-dependent pressor response (10-320 micromol/kg). CA (80 micromol/kg) induced a depressor response that was significantly less in TRPA1 KO mice, with minimal pressor effects. The pressor response of a higher CA dose (320 micromol/kg) was observed in WT but not in TRPA1 KO mice, indicating involvement of TRPA1. Experiments using TRP vanilloid 1 (TRPV1) KO and calcitonin gene-related peptide (CGRP) KO mice provided little evidence for the involvement of TRPV1 or CGRP, nor did blocking substance P receptors affect responses. However, the cholinergic antagonist atropine sulphate (5 mg/kg) significantly inhibited the depressor response and slowed HR with CA (80 micromol/kg), but had no effect on pressor responses. The pressor response remained unaffected, even in the presence of the ganglion blocker hexamethonium bromide (1 mg/kg). The alpha-adrenergic blocker prazosin hydrochloride (1 mg/kg) significantly inhibited both components, but not slowed HR.
TRPA1 is involved in mediating vasodilation. TRPA1 can also influence changes in blood pressure of possible relevance to autonomic system reflexes and potentially to vasovagal/neurocardiogenic syncope disorders.
本研究旨在探讨瞬时受体电位锚蛋白 1（TRPA1）在血管和血压及心率（HR）中的作用，使用野生型（WT）和 TRPA1 敲除（KO）小鼠研究 TRPA1 激动剂。
TRPA1 激动剂丙烯基异硫氰酸酯和肉桂醛（CA）可显著增加麻醉 WT 小鼠皮肤的血流量，但在 TRPA1 KO 小鼠中则无此作用。CA 还可诱导肠系膜动脉的 TRPA1 依赖性舒张。静脉注射 CA 引起短暂的血压下降，同时 HR 降低，这种反应取决于基因型和剂量，随后是更持续的、剂量依赖性的升压反应（10-320 μmol/kg）。CA（80 μmol/kg）引起的降压反应在 TRPA1 KO 小鼠中明显减弱，升压作用最小。较高 CA 剂量（320 μmol/kg）引起的升压反应仅在 WT 小鼠中观察到，而在 TRPA1 KO 小鼠中则未观察到，表明 TRPA1 参与其中。使用 TRPV1 敲除（TRPV1 KO）和降钙素基因相关肽（CGRP）敲除（CGRP KO）小鼠的实验结果表明，TRPV1 或 CGRP 参与度较低，阻断 P 物质受体也不会影响反应。然而，胆碱能拮抗剂硫酸阿托品（5 mg/kg）可显著抑制 CA（80 μmol/kg）引起的降压反应和 HR 减慢，但对升压反应无影响。即使存在神经节阻滞剂六烃季铵（1 mg/kg），升压反应也不受影响。α-肾上腺素能阻滞剂盐酸普萘洛尔（1 mg/kg）可显著抑制这两个成分，但不能减缓 HR。
TRPA1 参与介导血管扩张。TRPA1 还可以影响血压变化，这可能与自主神经系统反射有关，并可能与血管迷走性/神经心源性晕厥障碍有关。
