Packer R K, Desai S S, Hornbuckle K, Knepper M A
Laboratory of Kidney and Electrolyte Metabolism, National Heart, Lung, and Blood Institute, National Institute of Health, Bethesda, MD.
J Am Soc Nephrol. 1991 Jul;2(1):77-83. doi: 10.1681/ASN.V2177.
Ammonium (NH3 plus NH4+), produced predominantly in the proximal tubule, is transferred to the final urine by a process involving countercurrent multiplication of ammonium which generates an ammonium concentration gradient in the renal medulla. It was hypothesized that if urinary ammonium excretion rates are controlled in part by the medullary ammonium gradient, changes in hydration and acid-base state should cause changes in the medullary ammonium gradient consistent with expected changes in urinary ammonium concentrations. To test that hypothesis, rats were subjected to water diuresis, water deprivation, water deprivation plus furosemide, and dietary acid and base loads and corticomedullary ammonium gradients in their kidneys were then measured. Sections were cut along the corticomedullary axis to yield slices of cortex, outer stripe of outer medulla, inner stripe of outer medulla, and three levels of the inner medulla. The total ammonia content of homogenized slices was measured by either a membrane ammonia electrode or an enzymatic technique. Kidneys from water-deprived animals showed a distinct ammonium gradient along the corticomedullary axis, with the highest contents found at the tip of the papilla. The gradient was attenuated by water diuresis and abolished by furosemide. Acid loading enhanced the gradient, and base loading abolished it. These results indicate that the corticomedullary ammonium gradient is regulated in response to changes in hydration and acid-base state.
铵（NH₃加NH₄⁺）主要在近端小管产生，通过一个涉及铵逆流倍增的过程转移到终尿中，该过程在肾髓质中产生铵浓度梯度。据推测，如果尿铵排泄率部分受髓质铵梯度控制，那么水合状态和酸碱状态的变化应会导致髓质铵梯度发生变化，这与尿铵浓度的预期变化一致。为了验证这一假设，对大鼠进行水利尿、禁水、禁水加呋塞米处理，以及给予饮食性酸负荷和碱负荷，然后测量其肾脏的皮质髓质铵梯度。沿皮质髓质轴切片，得到皮质、外髓质外带、外髓质内带以及内髓质三个层面的切片。用膜氨电极或酶法技术测量匀浆切片的总氨含量。禁水动物的肾脏沿皮质髓质轴呈现出明显的铵梯度，在乳头尖端含量最高。该梯度在水利尿时减弱，在使用呋塞米后消失。酸负荷增强了该梯度，而碱负荷则使其消失。这些结果表明，皮质髓质铵梯度会根据水合状态和酸碱状态的变化而受到调节。
