Abdulnour-Nakhoul Solange, Hering-Smith Kathleen, Hamm L Lee, Nakhoul Nazih L
Section of Nephrology, Departments of Medicine and Physiology, Tulane University School of Medicine, New Orleans, Louisiana.
Physiol Rep. 2019 Aug;7(16):e14221. doi: 10.14814/phy2.14221.
Hypercapnia and subsequent respiratory acidosis are serious complications in many patients with respiratory disorders. The acute response to hypercapnia is buffering of H by hemoglobin and cellular proteins but this effect is limited. The chronic response is renal compensation that increases HCO reabsorption, and stimulates urinary excretion of titratable acids (TA) and NH . However, the main effective pathway is the excretion of NH in the collecting duct. Our hypothesis is that, the renal NH /NH transporters, Rhbg and Rhcg, in the collecting duct mediate this response. The effect of hypercapnia on these transporters is unknown. We conducted in vivo experiments on mice subjected to chronic hypercapnia. One group breathed 8% CO and the other breathed normal air as control (0.04% CO ). After 3 days, the mice were euthanized and kidneys, blood, and urine samples were collected. We used immunohistochemistry and Western blot analysis to determine the effects of high CO on localization and expression of the Rh proteins, carbonic anhydrase IV, and pendrin. In hypercapnic animals, there was a significant increase in urinary NH excretion but no change in TA. Western blot analysis showed a significant increase in cortical expression of Rhbg (43%) but not of Rhcg. Expression of CA-IV was increased but pendrin was reduced. These data suggest that hypercapnia leads to compensatory upregulation of Rhbg that contributes to excretion of NH /NH in the kidney. These studies are the first to show a link among hypercapnia, NH excretion, and Rh expression.
高碳酸血症及随后的呼吸性酸中毒是许多呼吸系统疾病患者的严重并发症。对高碳酸血症的急性反应是血红蛋白和细胞蛋白对H的缓冲作用，但这种作用有限。慢性反应是肾脏代偿，可增加HCO重吸收，并刺激可滴定酸（TA）和NH的尿排泄。然而，主要的有效途径是集合管中NH的排泄。我们的假设是，集合管中的肾脏NH/NH转运体Rhbg和Rhcg介导了这种反应。高碳酸血症对这些转运体的影响尚不清楚。我们对遭受慢性高碳酸血症的小鼠进行了体内实验。一组小鼠呼吸8%的CO，另一组呼吸正常空气作为对照（0.04%的CO）。3天后，对小鼠实施安乐死并采集肾脏、血液和尿液样本。我们使用免疫组织化学和蛋白质印迹分析来确定高CO对Rh蛋白、碳酸酐酶IV和pendrin的定位及表达的影响。在高碳酸血症动物中，尿NH排泄显著增加，但TA无变化。蛋白质印迹分析显示，Rhbg的皮质表达显著增加（43%），但Rhcg没有变化。CA-IV的表达增加，但pendrin减少。这些数据表明，高碳酸血症导致Rhbg代偿性上调，这有助于肾脏中NH/NH的排泄。这些研究首次表明了高碳酸血症、NH排泄和Rh表达之间的联系。
