Jougasaki M, Wei C M, Aarhus L L, Heublein D M, Sandberg S M, Burnett J C
Cardiorenal Research Laboratory, Mayo Clinic and Foundation, Rochester, Minnesota 55905, USA.
Am J Physiol. 1995 Apr;268(4 Pt 2):F657-63. doi: 10.1152/ajprenal.1995.268.4.F657.
Adrenomedullin (ADM) is a newly described 52-amino acid peptide originally isolated from extracts of human pheochromocytoma and, more recently, detected in human plasma. Based on the report that ADM mRNA and immunoreactivity are present in the kidney, the current study was designed to determine the renal distribution of ADM by immunohistochemistry and the renal biological actions of ADM. In the immunohistochemical studies, the present investigation demonstrated the localization of ADM in glomeruli, cortical distal tubules, and medullary collecting duct cells of the normal canine kidney. In the in vivo studies, ADM was administered (0.25 ng.kg-1.min-1 in group I and 1, 5, and 25 ng.kg-1.min-1 in group II) intrarenally in normal mongrel dogs with the contralateral kidney receiving only saline vehicle. Intrarenal infusion of ADM resulted in a marked diuretic and natriuretic response, whereas the contralateral kidney showed no renal effects. These significant natriuresis and diuresis in the ADM kidney were associated with increases in glomerular filtration rate and fractional sodium excretion and with a decrease in distal tubular sodium reabsorption. Intrarenal infusion of ADM also caused an increase in mean arterial blood pressure and a decrease in heart rate. Plasma concentrations of atrial natriuretic peptide, renin activity, aldosterone, and guanosine 3',5'-cyclic monophosphate were not changed during the infusion of ADM. The current study demonstrates that ADM is present in renal glomerular and tubular cells and is a potent natriuretic peptide that may play an important role in the regulation of sodium excretion.
肾上腺髓质素（ADM）是一种新发现的由52个氨基酸组成的肽，最初从人嗜铬细胞瘤提取物中分离出来，最近在人血浆中也被检测到。基于ADM信使核糖核酸（mRNA）和免疫反应性存在于肾脏的报道，本研究旨在通过免疫组织化学确定ADM在肾脏中的分布以及ADM的肾脏生物学作用。在免疫组织化学研究中，本调查显示ADM在正常犬肾的肾小球、皮质远端小管和髓质集合管细胞中定位。在体内研究中，将ADM（第一组为0.25纳克·千克-1·分钟-1，第二组为1、5和25纳克·千克-1·分钟-1）经肾内给予正常杂种犬，对侧肾脏仅给予生理盐水载体。肾内输注ADM导致明显的利尿和利钠反应，而对侧肾脏未显示肾脏效应。ADM处理的肾脏中这些显著的利钠和利尿与肾小球滤过率和钠排泄分数增加以及远端小管钠重吸收减少有关。肾内输注ADM还导致平均动脉血压升高和心率降低。在输注ADM期间，心房利钠肽、肾素活性、醛固酮和鸟苷3',5'-环磷酸的血浆浓度未发生变化。本研究表明，ADM存在于肾肾小球和肾小管细胞中，是一种有效的利钠肽，可能在钠排泄调节中起重要作用。
