[精氨酸加压素对大鼠失血性休克后血管反应性、血管平滑肌钙敏感性及其与蛋白激酶C关系的影响]

[Effect of arginine vasopressin on vascular reactivity and calcium sensitivity of vascular smooth muscle and its relationship to protein kinase C following hemorrhagic shock in rats].

作者信息

Yang Guang-ming, Li Tao, Xu Jing, Ming Jia, Liu Liang-ming

机构信息

State Key Laboratory of Trauma, Burns and Combined Injury, Department 2, Research Institute of Surgery, Daping Hospital, The Third Military Medical University, Chongqing 400042, China.

出版信息

Zhongguo Wei Zhong Bing Ji Jiu Yi Xue. 2008 Mar;20(3):139-43.

PMID:18328123

Abstract

OBJECTIVE

To investigate the effect of arginine vasopressin (AVP) on vascular reactivity and calcium sensitivity following hemorrhagic shock and their relationship to protein kinase C (PKC) isoforms.

METHODS

With endothelium denuded superior mesenteric artery (SMA) rings procured from rats in hemorrhagic shock, the effects of AVP (5x10(-11), 5x10(-10) and 5x10(-9) mol/L) on contractile responses to norepinephrine (NE) and calcium sensitivity of SMA from hemorrhagic shock in rats and their relationship to alpha and Delta isoforms of PKC with isolated organ perfusion system were observed.

RESULTS

AVP (5x10(-11), 5x10(-10) and 5x10(-9) mol/L) markedly restored the vascular reactivity and calcium sensitivity following hemorrhagic shock, converting the cumulative concentration-response curve of NE and Ca2+ shift to the left, and its maximum concentration force (Emax) was significantly increased (all P<0.01) in a concentration dependent manner. Significant statistical differences were observed between the AVP groups (all P<0.05). Go6976 (5x10(-6) mol/L) and Rottlerin (10(-5) mol/L),respectively as the specific PKC alpha and PKC Delta isoforms inhibitor, antagonized AVP (5x10(-10) mol/L)-induced increase in vascular reactivity and calcium sensitivity of SMA following hemorrhagic shock and inhibited AVP-induced shift to the left of cumulative concentration-response curve of NE and Ca2+, and the Emax was significantly decreased (P<0.05 or P<0.01).

CONCLUSION

AVP significantly restored the decreased vascular reactivity and calcium sensitivity of vascular smooth muscle following hemorrhagic shock, and its underlying mechanisms may be related to both alpha and Delta isoforms of PKC activation.

摘要

目的

探讨精氨酸加压素（AVP）对失血性休克后血管反应性和钙敏感性的影响及其与蛋白激酶C（PKC）亚型的关系。

方法

采用失血性休克大鼠的去内皮肠系膜上动脉（SMA）环，利用离体器官灌注系统观察AVP（5×10⁻¹¹、5×10⁻¹⁰和5×10⁻⁹ mol/L）对失血性休克大鼠SMA对去甲肾上腺素（NE）的收缩反应和钙敏感性的影响及其与PKCα和PKCδ亚型的关系。

结果

AVP（5×10⁻¹¹、5×10⁻¹⁰和5×10⁻⁹ mol/L）显著恢复失血性休克后的血管反应性和钙敏感性，使NE和Ca²⁺的累积浓度-反应曲线左移，其最大浓度力（Emax）以浓度依赖性方式显著增加（均P<0.01）。AVP各剂量组间差异有统计学意义（均P<0.05）。Go6976（5×10⁻⁶ mol/L）和罗特lerin（10⁻⁵ mol/L）分别作为PKCα和PKCδ亚型特异性抑制剂，拮抗AVP（5×10⁻¹⁰ mol/L）诱导的失血性休克后SMA血管反应性和钙敏感性增加，抑制AVP诱导的NE和Ca²⁺累积浓度-反应曲线左移，Emax显著降低（P<0.05或P<0.01）。