Jougasaki M, Aarhus L L, Heublein D M, Sandberg S M, Burnett J C
Cardiorenal Research Laboratory, Division of Cardiovascular Diseases, Mayo Clinic and Foundation, Rochester, Minnesota 55905, USA.
Am J Physiol. 1997 Feb;272(2 Pt 2):F260-6. doi: 10.1152/ajprenal.1997.272.2.F260.
Adrenomedullin (ADM), originally discovered in human pheochromocytoma, is also of renal cell origin and has natriuretic and diuretic actions. The present study was designed to investigate the role of prostaglandins and renal nerves in the renal hemodynamic and natriuretic actions ofADM. ADM was administered intrarenally (1, 5 and 25 ng x kg(-1) x min(-1)) with and without prostaglandin inhibition (meclofenamate, 5 mg/kg intravenous bolus) in anesthetized normal mongrel dogs (n = 5, each). To elucidate the role of renal nerves, ADM was administered intrarenally to the denervated kidney in five dogs. ADM mediated a natriuretic action via increases in glomerular filtration rate and decreases in distal tubular sodium reabsorption, which was attenuated by renal denervation and completely abolished by prostaglandin inhibition. The renal vasodilatation induced by ADM was attenuated by meclofenamate, as well as by renal denervation, although not significantly. Additionally, renal nerves mediated hemodynamic effects of hypertension that were produced by intrarenal infusion of ADM. This study establishes an important mechanistic role for renal prostaglandins as a mediator of ADM-mediated natriuresis at the level of the glomerulus and terminal nephron.
肾上腺髓质素（ADM）最初是在人类嗜铬细胞瘤中发现的，它也起源于肾细胞，具有利钠和利尿作用。本研究旨在探讨前列腺素和肾神经在ADM的肾血流动力学和利钠作用中的作用。在麻醉的正常杂种犬（每组n = 5）中，分别在有和没有前列腺素抑制（甲氯芬那酸，5 mg/kg静脉推注）的情况下，经肾给予ADM（1、5和25 ng·kg⁻¹·min⁻¹）。为了阐明肾神经的作用，对5只犬的去神经支配肾脏经肾给予ADM。ADM通过增加肾小球滤过率和减少远端肾小管钠重吸收介导利钠作用，这种作用在肾去神经支配后减弱，在前列腺素抑制后完全消失。ADM诱导的肾血管舒张被甲氯芬那酸以及肾去神经支配减弱，尽管不显著。此外，肾神经介导了肾内输注ADM所产生的高血压的血流动力学效应。本研究确立了肾前列腺素作为ADM介导的肾小球和终末肾单位水平利钠作用的介质的重要机制作用。
