Transient receptor potential vainilloid 1 antagonist, capsazepine, improves survival in a rat hemorrhagic shock model
Transient receptor potential vainilloid 1 antagonist, capsazepine, improves survival in a rat hemorrhagic shock model
复制标题
DOI：
10.1097/01.sla.0000255577.80800.e1
复制
发表时间：
2007-06-01
影响因子：
9
通讯作者：
Tani, Tohru
中科院分区：
文献类型：
--
作者：
Akabori, Hiroya;Yamamoto, Hiroshi;Tani, Tohru
目的：探讨瞬时受体电位香草素1 （TRPV1）在大鼠失血性休克（HS）模型中的作用，应用TRPV1拮抗剂辣椒平（CPZ）。背景资料：TRPV1分布于感觉神经内，参与心血管功能的调节。TRPV1可能参与心血管对HS的反应。方法：雄性大鼠麻醉后，以平均动脉压（MAP） 30 mm Hg诱导HS 90 min。休克诱导后30分钟给予CPZ (5.0 mu mol/kg)，评估24小时存活率。在整个实验过程中记录MAP、心率和血流量（SBV）。测定HS前后动脉血气分析及血浆儿茶酚胺水平。采用双免疫组化法对脑前腹外侧髓质（RVLM）进行Fos和酪氨酸羟化酶（TH）的检测。结果：CPZ显著提高24小时生存率，同时伴有MAP和SBV升高，血浆儿茶酚胺水平降低，重度代谢性酸中毒减轻。此外，CPZ降低了大鼠脑RVLM中Fos和TH双标记神经元的百分比。结论：TRPV1可能通过募集RVLM中的儿茶酚胺能神经元参与调节心血管对HS的反应，至少部分参与。CPZ似乎可以诱导代谢代偿，这可能对HS有潜在的作用。
Objective: To evaluate the role of transient receptor potential vanilloid 1 (TRPV1) in a rat hemorrhagic shock (HS) model using the TRPV1 antagonist, capsazepine (CPZ).Summary Background Data: TRPV1, distributed within the sensory nerve, plays a role in the regulation of cardiovascular functions. TRPV1 may be involved in the cardiovascular responses to HS.Methods: Male rats were anesthetized and HS was induced with the mean arterial pressure (MAP) at 30 mm Hg for 90 minutes. CPZ (5.0 mu mol/kg) was administered at 30 minutes after the shock induction, and the 24-hour survival rates were assessed. The MAP, heart rate, and shed blood volume (SBV) were recorded throughout the experiment. Arterial blood gas analysis and the plasma catecholamines levels were measured before and after HS. Double-immunohistochemistry for Fos and tyrosine hydroxylase (TH) was performed in the rostral ventrolateral medulla (RVLM) of the brain.Results: CPZ significantly improved the 24-hour survival rates, which was accompanied by the increase in the MAP and the SBV, a decrease of the plasma catecholamines levels, and attenuation of the severe metabolic acidosis. Furthermore, CPZ reduced the percentage of double-labeled neurons for Fos and TH in the RVLM of the rat brain.Conclusions: TRPV1 may be involved in the regulation of the cardiovascular responses to HS, at least in part, by recruiting catecholaminergic neurons in the RVLM. CPZ appears to induce metabolic compensations, which may be potentially useful in HS.