Jougasaki M, Heublein D M, Sandberg S M, Burnett J C
Cardiorenal Research Laboratory, Division of Cardiovascular Diseases, Mayo Clinic and Foundation, Rochester, Minnesota 55905, USA.
J Card Fail. 2001 Mar;7(1):75-83. doi: 10.1054/jcaf.2001.23233.
The recently discovered vasodilating and positive inotropic peptide, adrenomedullin (ADM), has strong natriuretic actions. ADM-induced natriuresis is caused by an increase in glomerular filtration rate and a decrease in distal tubular sodium reabsorption. Although ADM is activated in human and experimental heart failure, the role of ADM in the kidney in heart failure remains undefined.
The present study was performed to determine the renal hemodynamic and urinary excretory actions of exogenously administered ADM in a canine model of acute heart failure produced by rapid ventricular pacing. Experimental acute heart failure was characterized by a decrease in cardiac output and an increase in pulmonary capillary wedge pressure with an increase in plasma ADM concentration. Intrarenal infusion of ADM (1 and 25 ng/kg/min) induced an increase in urinary sodium excretion in the normal control dogs (change in urinary sodium excretion [Delta UNaV], +94.5 microEq/min during 1 ng/kg/min ADM infusion and +128.1 microEq/min during 25 ng/kg/min ADM infusion). In the acute heart failure dogs, intrarenal ADM infusion resulted in an attenuated increase in urinary sodium excretion (Delta UNaV, +44.8 microEq/min during 1 ng/kg/min ADM infusion and +51.8 microEq/min during 25 ng/kg/min ADM infusion). Both glomerular and tubular actions of ADM were attenuated in the acute heart failure group compared with responses in the normal control group.
The present study shows that the renal natriuretic responses to ADM are markedly attenuated in experimental acute heart failure. This study provides insight into humoral mechanisms that may promote sodium retention in heart failure via a renal hyporesponsiveness to natriuretic actions of ADM.
最近发现的血管舒张和正性肌力肽——肾上腺髓质素（ADM）具有强大的利钠作用。ADM诱导的利钠作用是由肾小球滤过率增加和远端肾小管钠重吸收减少引起的。尽管ADM在人类和实验性心力衰竭中被激活，但其在心力衰竭时肾脏中的作用仍不明确。
本研究旨在确定在快速心室起搏产生的犬急性心力衰竭模型中外源性给予ADM的肾脏血流动力学和尿排泄作用。实验性急性心力衰竭的特征是心输出量减少、肺毛细血管楔压升高以及血浆ADM浓度增加。在正常对照犬中，肾内输注ADM（1和25 ng/kg/min）导致尿钠排泄增加（尿钠排泄变化量[ΔUNaV]，在输注1 ng/kg/min ADM时为+94.5微当量/分钟，在输注25 ng/kg/min ADM时为+128.1微当量/分钟）。在急性心力衰竭犬中，肾内输注ADM导致尿钠排泄增加减弱（ΔUNaV，在输注1 ng/kg/min ADM时为+44.8微当量/分钟，在输注25 ng/kg/min ADM时为+51.8微当量/分钟）。与正常对照组相比，急性心力衰竭组中ADM的肾小球和肾小管作用均减弱。
本研究表明，在实验性急性心力衰竭中，肾脏对ADM的利钠反应明显减弱。该研究为可能通过肾脏对ADM利钠作用反应低下促进心力衰竭时钠潴留的体液机制提供了见解。
