The spleen is required for 5-HT1A receptor agonist-mediated increases in mean circulatory filling pressure during hemorrhagic shock in the rat.

The spleen is required for 5-HT1A receptor agonist-mediated increases in mean circulatory filling pressure during hemorrhagic shock in the rat.
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大鼠失血性休克期间,5-HT1A 受体激动剂介导的平均循环充盈压增加需要脾脏。

DOI:
10.1152/ajpregu.91055.2008
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发表时间:
2009
期刊:
American journal of physiology. Regulatory, integrative and comparative physiology
影响因子:
--
通讯作者:
Scrogin,KarieE
Scrogin,KarieE
中科院分区:
--
文献类型:
--
作者:
Tiniakov,Ruslan;Scrogin,KarieE

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5-HT1A 受体激动剂 8-OH-DPAT 可增加全身静脉张力(平均循环充盈压;MCFP),并减轻未复苏失血性休克大鼠模型中的代谢性酸中毒。为了确定酸碱平衡的改善是否与交感神经激活和静脉收缩相关,对给予 5-HT1A 受体激动剂 8-OH-DPAT、动脉血管收缩剂精氨酸加压素 (AVP) 或生理盐水后的出血大鼠进行了 MCFP、交感神经活性 (SA) 和血气分析。为了进一步确定酸碱平衡的保护是否依赖于脾收缩和血液动员,在接受真脾切除术或假脾切除术的大鼠中,在出血和随后施用 8-OH-DPAT 期间测定了中心静脉压 (CVP)、MCFP 和血气。受试者出血至动脉压 50 mmHg,持续 25 分钟,随后接受 8-OH-DPAT(30 nmol/kg iv)治疗,滴定 AVP 以匹配 8-OH-DPAT(∼2 ng/min iv)的升压作用,或输注生理盐水。 8-OH-DPAT 增加 MAP、CVP、MCFP 和 SA,并减少乳酸积累。 AVP 不影响 CVP 或 SA,但将 MCFP 略微升高至 8-OH-DPAT 和盐水处理大鼠之间的中间水平。输注 AVP 还可对代谢性酸中毒产生一定的保护作用。脾切除术可防止 CVP、MCFP 的升高,并防止 8-OH-DPAT 产生的代谢性酸中毒,但对药物的即时升压反应没有影响。总之,数据表明 8-OH-DPAT 产生的心血管反应模式与交感神经介导的静脉收缩一致,这在一定程度上是该药物对酸碱平衡产生有益作用的原因。此外,8-OH-DPAT 的有益作用需要脾脏刺激的血液动员。
The 5-HT1Areceptor agonist, 8- OH-DPAT, increases whole body venous tone (mean circulatory filling pressure; MCFP), and attenuates metabolic acidosis in a rat model of unresuscitated hemorrhagic shock. To determine whether improved acid-base balance was associated with sympathetic activation and venous constriction, MCFP, sympathetic activity (SA), and blood gases were compared in hemorrhaged rats following administration of 5-HT1Areceptor agonist 8-OH-DPAT, the arterial vasoconstrictor arginine vasopressin (AVP), or saline. To further determine whether protection of acid-base balance was dependent on splenic contraction and blood mobilization, central venous pressure (CVP), MCFP, and blood gases were determined during hemorrhage and subsequent 8-OH-DPAT-administration in rats subjected to real or sham splenectomy. Subjects were hemorrhaged to an arterial pressure of 50 mmHg for 25 min and subsequently were treated with 8-OH-DPAT (30 nmol/kg iv), AVP titrated to match the pressor effect of 8-OH-DPAT (∼2 ng/min iv), or infusion of normal saline. 8-OH-DPAT increased MAP, CVP, MCFP, and SA, and decreased lactate accumulation. AVP did not affect CVP or SA, but raised MCFP slightly to a level intermediate between 8-OH-DPAT- and saline-treated rats. Infusion of AVP also produced a modest protection against metabolic acidosis. Splenectomy prevented the rise in CVP, MCFP, and protection against metabolic acidosis produced by 8-OH-DPAT but had no effect on the immediate pressor response to the drug. Together, the data indicate that 8-OH-DPAT produces a pattern of cardiovascular responses consistent with a sympathetic-mediated venoconstriction that is, in part, responsible for the drug's beneficial effect on acid-base balance. Moreover, blood mobilization stimulated by the spleen is required for the beneficial effects of 8-OH-DPAT.