精氨酸加压素对失血性休克大鼠血管反应性的影响

Effect of arginine vasopressin on vasoreactivity in hemorrhagic shock rats

目的探讨精氨酸加压素(AVP)对失血性休克大鼠血管反应性的影响,并初步探讨其与Rho激酶的关系。方法在体实验,观察大鼠失血性休克后AVP对去甲肾上腺素(NE)升压反应的影响;离体实验,测定失血性休克大鼠肠系膜上动脉(SMA)环对NE的收缩反应和去极化状态下(120mmol·L-1K+)对Ca2+的收缩反应,反映其对缩血管物质和钙的反应性。结果失血性休克(4kPa,2h)后大鼠对NE的升压反应显著下降。AVP0.1和0.4U·kg-1,iv,随后再将AVP溶于3倍失血量的复方氯化钠溶液分别以0.01和0.04U·kg-1·min-1的速度于30min内用输液泵输注,3～4h后可使NE的升压反应恢复至正常组水平。失血性休克后SMA对NE和钙的反应性显著下降,对NE和Ca2+的收缩反应量效曲线明显右移,最大反应(Emax)降低;加入NE和Ca2+前分别用0.5和5nmol·L-1AVP孵育10min可使NE和Ca2+的收缩反应量效曲线明显左移,Emax显著增高。Rho激酶拮抗剂HA1077预处理可部分取消AVP所致的Ca2+Emax变化,使Emax回降。结论AVP能升高失血性休克大鼠血管对NE的敏感性及反应效能和血管平滑肌对钙的反应效能。

AIM To investigate the effects of arginine vasopressin （AVP） on vascular response following hemorrhagic shock in rats and its relations with Rho-kinase. METHODS Effect of AVP （0.1 and 0.4 U·kg^-1） on pressor effect of norepinephrine （NE） in hemorrhagic shock（4 kPa for 2 h） rats was observed in vivo. In vitro, the contractile response of superior mesenteric artery （SMA） from hemorrhagic shock rats to NE and its contractile response to Ca^2＋ under depolarizing conditions （120 mmol·L^-1 K^＋） were observed. RESULTS The NE-induced pressor response following hemorrhagic shock was significantly decreased. At 3-4 h after AVP administration （an initial bolus of AVP 0.1 or 0.4 U·kg^-1, iv, followed by a continuous infusion of AVP at a rate of 0.1 or 0.4 U·kg^-1·min^-1 with three volumes of compound sodium chloride solution for 30 rain by infusion pump）, the pressor effect of NE was nearly close to the control group in vivo. The contractile response of SMA to NE and Ca^2＋ following hemorrhagic shock was significantly decreased as compared with the control group, its cumulative dose-response curve was significantly shifted to the right, the Emax were significantly decreased. AVP pretreatment （AVP 0.5, 5 nmol·L^-1 was added 10 min before NE and CaCl2 addtion）, significantly increased the contractile response of SMA to NE and Ca^2＋ and made the cumulative dose-response curve of NE and Ca^2＋ shift to the left, the Emax were significantly increased. HA-1077, the Rho-kinase antagonist, partly antagonized AVP-induced leftward shift of the dose-response curve of Ca^2＋, the Emax were decreased. CONCLUSION AVP can increase the vascular sensitivity and efficacy to NE and efficacy to calcium of SMA in hemorrhagic shock rats.