Nakamura Motonobu, Shirai Ayumi, Yamazaki Osamu, Satoh Nobuhiko, Suzuki Masashi, Horita Shoko, Yamada Hideomi, Seki George
Department of Internal Medicine, Faculty of Medicine, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-0033, Japan.
Biomed Res Int. 2014;2014:504808. doi: 10.1155/2014/504808. Epub 2014 May 28.
Sodium-coupled bicarbonate absorption from renal proximal tubules (PTs) plays a pivotal role in the maintenance of systemic acid/base balance. Indeed, mutations in the Na(+)-HCO3 (-) cotransporter NBCe1, which mediates a majority of bicarbonate exit from PTs, cause severe proximal renal tubular acidosis associated with ocular and other extrarenal abnormalities. Sodium transport in PTs also plays an important role in the regulation of blood pressure. For example, PT transport stimulation by insulin may be involved in the pathogenesis of hypertension associated with insulin resistance. Type 1 angiotensin (Ang) II receptors in PT are critical for blood pressure homeostasis. Paradoxically, the effects of Ang II on PT transport are known to be biphasic. Unlike in other species, however, Ang II is recently shown to dose-dependently stimulate human PT transport via nitric oxide/cGMP/ERK pathway, which may represent a novel therapeutic target in human hypertension. In this paper, we will review the physiological and pathophysiological roles of PT transport.
肾近端小管（PT）对钠耦联的碳酸氢盐的重吸收在维持全身酸碱平衡中起关键作用。实际上，钠-碳酸氢根共转运体NBCe1介导了大部分从近端小管排出的碳酸氢盐，该转运体发生突变会导致严重的近端肾小管酸中毒，并伴有眼部及其他肾外异常。近端小管中的钠转运在血压调节中也起重要作用。例如，胰岛素对近端小管转运的刺激作用可能参与了与胰岛素抵抗相关的高血压的发病机制。近端小管中的1型血管紧张素（Ang）II受体对血压稳态至关重要。矛盾的是，已知Ang II对近端小管转运的作用具有双相性。然而，与其他物种不同的是，最近研究表明，Ang II通过一氧化氮/cGMP/ERK途径剂量依赖性地刺激人类近端小管转运，这可能是人类高血压的一个新的治疗靶点。在本文中，我们将综述近端小管转运的生理和病理生理作用。
