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分级失血性休克期间一氧化氮合酶内源性抑制剂的蓄积

Accumulation of an endogenous inhibitor of nitric oxide synthase during graded hemorrhagic shock.

作者信息

Aneman A, Backman V, Snygg J, von Bothmer C, Fändriks L, Pettersson A

机构信息

Department of Physiology, University of Göteborg, Gothenburg, Sweden.

出版信息

Circ Shock. 1994 Nov;44(3):111-4.

PMID:7541318
Abstract

Asymmetric dimethylarginine (ADMA) represents an endogenous inhibitor of nitric oxide (NO) production. The production of ADMA has been shown to increase during cellular stress, e.g., hypoxia. Furthermore, ADMA has recently been reported to accumulate in plasma during terminal renal failure as a consequence of diminished urinary excretion. Since tissue hypoxia and oliguria are both characteristics of severe hemorrhagic shock, this study was performed in order to establish whether plasma concentrations of ADMA increase during hemorrhagic shock. Six pigs were subjected to graded hemorrhage (20% and 40% of the calculated blood volume), resulting in significant (P < 0.05) reductions in blood pressure and cardiac output (from 98 +/- 4 to 36 +/- 5 mm Hg and from 3.0 +/- 0.2 to 1.4 +/- 0.2 L/min, respectively). Plasma ADMA concentrations as determined by high-performance liquid chromatography (HPLC) increased from a pre-hemorrhage value of 3.4 +/- 0.3 microM to 3.9 +/- 0.4 microM (ns) and 5.2 +/- 0.4 microM (P < 0.05), respectively. The present study demonstrates that plasma ADMA concentrations increase significantly during hemorrhagic shock. Thus, inhibition of the arginine-nitric oxide pathway as a result of ADMA accumulation, may represent an additional physiological mechanism to maintain systemic blood pressure in response to acute hypovolemia.

摘要

不对称二甲基精氨酸(ADMA)是一氧化氮(NO)生成的内源性抑制剂。研究表明,在细胞应激(如缺氧)期间,ADMA的生成会增加。此外,最近有报道称,终末期肾衰竭时,由于尿排泄减少,ADMA会在血浆中蓄积。鉴于组织缺氧和少尿都是严重失血性休克的特征,本研究旨在确定失血性休克期间血浆ADMA浓度是否会升高。对6头猪进行分级放血(放血量为计算血容量的20%和40%),导致血压和心输出量显著降低(P<0.05)(分别从98±4降至36±5mmHg,从3.0±0.2降至1.4±0.2L/min)。通过高效液相色谱法(HPLC)测定的血浆ADMA浓度分别从放血前的3.4±0.3μM升至3.9±0.4μM(无统计学意义)和5.2±0.4μM(P<0.05)。本研究表明,失血性休克期间血浆ADMA浓度显著升高。因此,ADMA蓄积导致的精氨酸-一氧化氮途径抑制可能是急性血容量不足时维持全身血压的另一种生理机制。

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