V_(1a)/V_2受体在精氨酸血管加压素恢复失血诱导大鼠血管低反应性中的作用

Effect of V_(1a) and V_2 receptor on the increase of vascular reactivity after hemorrhagic shock induced by arginine vasopressin

目的探讨精氨酸血管加压素(AVP)在恢复失血性休克动物血管反应性和钙敏感性中的可能机制和血管加压素V1 a、V2受体对其的作用。方法实验分2部分:在体实验,观察AVP(0.04、0.1、0.4 U/kg)对失血性休克大鼠肠系膜动脉(SMA)血管管径对去甲肾上腺素(NE)收缩反应性的影响;离体实验,取失血性休克大鼠SMA环,利用离体血管环张力测定技术,观察V1 a和V2受体拮抗剂对AVP恢复失血性休克大鼠肠系膜动脉反应性和钙敏感性的影响。结果失血性休克后,大鼠肠系膜动脉对NE的收缩反应性明显降低,AVP各剂量均明显升高了休克大鼠SMA对NE的收缩反应。离体实验,AVP(5×10-10mol/L)可明显恢复休克后的血管低反应性和钙失敏;而AVP V1 a受体拮抗剂预处理可明显抑制AVP诱导的SMA对NE和Ca2+的反应性升高(P<0.01),V2受体拮抗剂也部分抑制了AVP的作用。结论AVP恢复失血性休克动物血管反应性和钙敏感性的机制与其V1 a和V2受体有关,其中V1 a受体可能发挥着更为重要的作用。

Objective To observe the effect of AVP on vascular reactivity and calcium sensitivity following hemorrhagic shock and its relations to V1a and V2 receptor in rats. Methods In vivo,the effects of AVP （0.04, 0.1 and 0.4U/kg） on the vasoconstriction of superior mesenteric artery （SMA） to norepinephrine （NE） were observed in hemorrhagic shock （30 mmHg for 2 hours） rats. In vitro, the effects of V1a and V2 receptor inhibitor on the increase of vascular reactivity and calcium sensitivity of SMA from hemorrhagic shock rats induced by arginine vasopressin were observed. Results In vivo, AVP （ 0.04,0.1 and 0.4U/kg ） significantly increased the vasoconstriction of SMA to NE in hemorrhagic shock rats,and in vitro,AVP （5 × 10^-10mol/L） pretreatment also improved reactivity of SMA to NE and calcium following hemorrhagic shock. The V1a receptor inhibitor significantly antagonized AVP-induced increase of vascular reactivity and calcium sensitivity of SMA following hemorrhagic shock and V2 receptor inhibitor also partly inhibited this effect. Conclusion AVP may restore the decreased vascular reactivity and calcium sensitivity of vascular smooth muscle after hemorrhagic shock through V1a and V2 receptor,and V1a receptor may play more important role than V2 receptor.