Ono Y, Kojima M, Okada K, Kangawa K
Department of Biochemistry, National Cardiovascular Center Research Institute, Suita, Osaka, Japan.
Shock. 1998 Oct;10(4):243-7. doi: 10.1097/00024382-199810000-00003.
Adrenomedullin (AM) is a potent vasorelaxing peptide isolated from human pheochromocytoma. It is proposed that AM dilates the blood vessels by autocrine or paracrine mechanisms. Our investigation concerned whether the vasodilating function of AM accounts for the hypotension occurring in endotoxin shock. The effect of endotoxin shock on AM gene expression in the cardiovascular system was probed using a canine model. The cDNA encoding the AM precursor in dogs was isolated from cDNA libraries of the adrenal gland and was sequenced. The canine AM precursor is constituted of 188 amino acids and its AM consists of 52 amino acids, similar to human and porcine AM. The dogs were injected intravenously with 2 mg/kg of lipopolysaccharide (LPS) after being anesthetized and intubated. After 4 h, we collected whole blood, the large and small blood vessels, and the heart from our canine model of endotoxin shock, and extracted RNA from those tissues for Northern blot analysis. In the endotoxin shock model, the mRNA levels of the AM had increased in almost all of the blood vessels. These results suggest that AM may dilate the blood vessels systemically, even if AM acts as a local modulator of vascular tone. In addition, the plasma concentrations of the AM were high enough to allow for AM to act as a vasodilating hormone. Consequently, AM may be one of the factors facilitating severe hypotension complicated with endotoxin shock.
肾上腺髓质素（AM）是一种从人嗜铬细胞瘤中分离出的强效血管舒张肽。有人提出，AM通过自分泌或旁分泌机制使血管扩张。我们的研究关注AM的血管舒张功能是否是内毒素休克中低血压发生的原因。使用犬模型探究内毒素休克对心血管系统中AM基因表达的影响。从肾上腺的cDNA文库中分离出编码犬AM前体的cDNA并进行测序。犬AM前体由188个氨基酸组成，其AM由52个氨基酸组成，与人和猪的AM相似。在对犬进行麻醉和插管后，静脉注射2mg/kg的脂多糖（LPS）。经过4小时，我们从内毒素休克犬模型中采集全血、大血管和小血管以及心脏，并从这些组织中提取RNA用于Northern印迹分析。在内毒素休克模型中几乎所有血管中AM的mRNA水平都升高了。这些结果表明，即使AM作为血管张力的局部调节剂，它也可能使全身血管扩张。此外，AM的血浆浓度高到足以使AM作为一种血管舒张激素发挥作用。因此，AM可能是促成内毒素休克并发严重低血压的因素之一。
