失血性休克大鼠血管平滑肌钙敏感性变化及其在休克双相血管反应性变化中的作用

Changes in sensitivity of vascular smooth muscle to calcium and its role in the biphasic change in vascular reactivity following hemorrhagic shock in rats

目的观察失血性休克后血管平滑肌钙敏感性是否存在双相变化,以及钙敏感性的双相变化与血管反应性双相变化的关系。方法取失血性休克大鼠肠系膜上动脉(SMA),采用离体血管环张力测定技术,观察在失血性休克后不同时间点(休克即刻、休克30min、休克1h、休克2h)大鼠SMA血管环对梯度浓度去甲肾上腺素(NE)的收缩反应性,以及在去极化状态下(120mmol/LK+)血管环对梯度浓度钙的收缩反应性变化(钙敏感性),分析血管反应性变化与钙敏感性变化的关系;同时观察钙敏感性增强剂血管紧张素(Ang)和钙敏感性抑制剂胰岛素对血管反应性的影响。结果休克早期(即休克即刻和休克30min时)SMA对NE和钙的反应性明显升高,量效曲线明显左移,最大收缩力(Emax)明显升高(P均<0.05);随着休克时间的延长,血管环对NE和钙的反应性均逐渐下降,到休克2h均已明显降低,其量效曲线明显右移,E-max明显降低(P<0.05或P<0.01);休克后不同时间点血管反应性变化与钙敏感性变化呈显著正相关(r=0.9624,P<0.05)。具有钙敏感性增强作用的Ang(1×10-9mol/L)可明显升高休克2h血管环对NE和钙的反应性(P<0.05或P<0.01),而有钙敏感性抑制作用的胰岛素则可降低休克早期(休克即刻)血管环对NE和钙的反应性(P<0.05或P<0.01)。结论失血性休克血管平滑肌细胞存在钙敏感性的双相变化,血管平滑肌细胞钙敏感性双相变化在失血性休克血管反应性的双相变化中起重要作用。

Objective To observe the change in sensitivity of vascular smooth muscle to calcium and its role in biphasic vascular reactivity following hemorrhagic shock （HS） in rats. Methods The superior mesenteric artery （SMA） obtained from rats with HS was used to assay the vascular reactivity and sensitivity to calcium by observing the contraction initiated by norepinephrine （NE） and Ca^2＋ under depolarizing conditions （120 mmol/L K^＋） with isolated organ perfusion system. At different time points after shock, the relationship between vascular reactivity and sensitivity to calcium was analyzed. Meanwhile the effects of the angiotensin Ⅱ （Ang Ⅱ ） and insulin, the calcium sensitivity regulating agents, on vascular reactivity were also observed. Results As compared with the control group, the cumulative dose - response curves of SMA to NE and Ca^2＋ at early shock stages, i.e. immediately and 30 minutes after shock, shifted to the left, the maximal contractions （Emax） of NE and Ca^2＋ were increased significantly （P〈0. 05 or P〈0. 01）. But the cumulative dose - response curves of SMA to NE and Ca^2＋ at late shock stage shifted to the right, and Emax of NE and Ca^2＋ were significantly decreased （P 〈 0.05 or P 〈 0.01）. Ang I increased the contractile response of SMA to NE and Ca^2＋ when shock persisted for 2 hours, rendering the cumulative dose - response curves of NE and Ca^2＋ shifted to the left （P〈0.05 or P〈0.01）. But insulin decreased the contractile response of SMA to NE and Ca^2＋ at early stage of shock, rendering the cumulative dose - response curves of NE and Ca^2＋ shifted to the right （P〈0. 05 or P〈0. 01）. Conclusion Sensitivity of vascular smooth muscle to calcium following hemorrhagia displays a biphasic change. It playes important roles in biphasic vascular reactivity.