Guarini S, Bazzani C, Tagliavini S, Bertolini A, Ferrari W
Institute of Pharmacology, University of Modena, Italy.
Neurosci Lett. 1992 Aug 31;143(1-2):181-4. doi: 10.1016/0304-3940(92)90261-5.
A volume-controlled hemorrhagic shock was produced in anesthetized rats by intermittent bleeding from an iliac vein over a period of 20-30 min, until the carotid mean arterial pressure (MAP) stabilized around 20-24 mmHg. In this condition, which caused the death of all saline-treated animals within 25-30 min, the intravenous (i.v.) bolus injection of the adrenocorticotropin fragment 1-24 (ACTH(1-24)) at a dose of 160 micrograms/kg promptly restored MAP, as well as pulse pressure, heart rate and respiratory function, and greatly prolonged the survival time. Capsaicin (125 mg/kg cumulatively, s.c., 1 week before) completely prevented the anti-shock effect of ACTH(1-24), which, on the other hand, was shared by i.v. [Nle11]-substance P (SP) (200-300 micrograms/kg). Finally the SP-antagonist [D-Arg1,D-Pro2,D-Trp7,9,Leu11]-SP prevented the effect of ACTH(1-24). These results suggest that SP-containing nerve fibers are required for the effect of ACTH in hemorrhagic shock.
通过从髂静脉间歇性放血20 - 30分钟，在麻醉大鼠中制造容量控制性失血性休克，直至颈动脉平均动脉压（MAP）稳定在20 - 24 mmHg左右。在这种情况下，所有接受生理盐水治疗的动物在25 - 30分钟内死亡，静脉推注剂量为160微克/千克的促肾上腺皮质激素片段1 - 24（ACTH(1 - 24)）能迅速恢复MAP、脉压、心率和呼吸功能，并大大延长存活时间。辣椒素（累积剂量125毫克/千克，皮下注射，1周前）完全阻断了ACTH(1 - 24)的抗休克作用，而静脉注射[Nle11]-P物质（SP）（200 - 300微克/千克）则具有相同作用。最后，SP拮抗剂[D - Arg1,D - Pro2,D - Trp7,9,Leu11]-SP阻断了ACTH(1 - 24)的作用。这些结果表明，含SP的神经纤维是ACTH在失血性休克中发挥作用所必需的。
