Unlike arginine vasopressin, the selective V1a receptor agonist FE 202158 does not cause procoagulant effects by releasing von Willebrand factor.
Unlike arginine vasopressin, the selective V1a receptor agonist FE 202158 does not cause procoagulant effects by releasing von Willebrand factor.
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DOI：
10.1097/ccm.0b013e31824e0fe5
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发表时间：
2012-06
影响因子：
8.8
通讯作者：
Traber DL
中科院分区：
文献类型：
--
作者：
Rehberg S;Enkhbaatar P;Rehberg J;La E;Ferdyan N;Qi S;Wisniewski K;Traber LD;Schteingart CD;Rivière PJ;Laporte R;Traber DL
比较1a型和2型加压素混合受体激动剂精氨酸加压素和选择性1a型加压素受体激动剂FE 202158 [Phe 2，Ile 3，Hgn 4，Orn（iPr）8]加压素在治疗感染性休克所需剂量下对血管性血友病因子释放的影响。前瞻性、随机、对照实验室实验。大学动物研究机构。24只慢性器械羊。经过5天的恢复，绵羊被随机分配接受单次静脉推注选择性血管加压素2型受体激动剂去氨加压素（1 nmol·kg−1）或持续静脉输注精氨酸加压素（3 pmol·kg−1·min−1）、选择性加压素1a型受体激动剂FE 202158（10 pmol·kg −1·min −1）或溶剂（0.9% NaCl）（各n = 6）。在120分钟的研究期间的不同时间点测量相对于血红蛋白浓度（vWF：Ag/Hb比值）的血管性血友病因子抗原活性。去氨加压素组（40 ± 6%，p<0.001）和精氨酸加压素组（25 ± 4%，p <0.001）的最大vWF：Ag/Hb比值（表示为基线水平的百分比）与赋形剂输注动物（3 ± 2%）相比显著增加。FE 202158组的比值与假手术组无统计学差异（9 ± 2%，p = 0.208）。值得注意的是，FE 202158组的最大vWF：Ag/Hb比值低于精氨酸加压素组（p<0.005）。与混合型血管加压素1a型受体/血管加压素2型受体激动剂精氨酸血管加压素不同，选择性血管加压素1a型受体激动剂FE 202158不释放血管性血友病因子。由于von Willebrand因子参与脓毒性休克期间的凝血和炎症途径，未来的研究应阐明精氨酸加压素引起的加压素2型受体介导的von Willebrand因子增加的作用，以及选择性加压素1a型受体激动剂（如FE 202158）的潜在益处。
To compare the effects on von Willebrand factor release of the mixed vasopressin type 1a and type 2 receptor agonist arginine vasopressin and the selective vasopressin type 1a receptor agonist FE 202158, [Phe2,Ile3,Hgn4,Orn(iPr)8]vasopressin, at doses required for the treatment of septic shock. Prospective, randomized, controlled laboratory experiment. University animal research facility. Twenty-four chronically instrumented sheep. After a 5-day recovery from instrumentation, sheep were randomly assigned to receive a single intravenous bolus of the selective vasopressin type 2 receptor agonist desmopressin (1 nmol·kg−1) or continuous intravenous infusions of arginine vasopressin (3 pmol·kg−1·min−1), the selective vasopressin type 1a receptor agonist FE 202158 (10 pmol·kg −1·min −1), or vehicle (0.9% NaCl) (n = 6 each). The von Willebrand factor antigen activity relative to hemoglobin concentration (vWF:Ag/Hb ratio) was measured at different time points during the 120-min study period. Maximal vWF:Ag/Hb ratio expressed as percentage of baseline level was significantly increased compared to vehicle-infused animals (3 ± 2%) in the desmopressin (40 ± 6%, p<.001) and arginine vasopressin groups (25 ± 4%, p<.001). The ratio for the FE 202158 group was not statistically different from the sham group (9 ± 2%, p = .208). Notably, maximal vWF:Ag/Hb ratio was lower in the FE 202158 than the arginine vasopressin group (p<.005). Unlike the mixed vasopressin type 1a receptor/vasopressin type 2 receptor agonist arginine vasopressin, the selective vasopressin type 1a receptor agonist FE 202158 does not release von Willebrand factor. Because von Willebrand factor is involved in coagulatory and inflammatory pathways during septic shock, future studies should clarify the role of the vasopressin type 2 receptor–mediated von Willebrand factor increase by arginine vasopressin and the potential benefit of selective vasopressin type 1a receptor–agonists like FE 202158.