Lee J Y, Prineas R J, Hallaway P E, Eaton J W
Am J Hematol. 1987 Sep;26(1):27-36. doi: 10.1002/ajh.2830260104.
The rate of influx of 22Na+ into human erythrocytes (RBC) varies greatly depending upon the donor. A high rate of influx may be related to a congenital predisposition to essential hypertension. In Northern Europeans, we find a threefold difference in the rate of 22Na+ influx between those with the least (LP) and most highly permeable (HP) RBC (from less than 0.15 to greater than 0.60 mmol Na+/liter RBC/hr). In order to further define determinants of these apparently hereditary differences in passive membrane Na+ transport, we identified two groups of normal laboratory and hospital personnel differing markedly (greater than twofold) in RBC 22Na+ influx rate. We find that the loop diuretics furosemide and bumetanide decrease by about 50% the influx of 22Na+ into HP RBC, but have a lesser influence on LP RBC. Impermeant polyanions such as citrate and pyrophosphate also specifically diminish 22Na+ influx into HP, but not LP, RBC. Therefore, the exaggerated 22Na+ influx into HP RBC probably occurs through a discrete pathway (perhaps via "Na/K/Cl cotransport"), which appears to be almost absent in LP RBC. The differences between HP and LP RBC most likely do not involve polymorphisms of RBC anion transport per se. The rate of RBC anion (35SO4(2-)) transport is the same in HP and LP RBC and is equally inhibited by furosemide and (to a lesser extent) bumetanide. Furthermore, the potent inhibitor of RBC anion transport, DIDS (diisothiocyanostilbene disulfonate) does not affect RBC Na+ permeability in either group. Nonetheless, the preferential reduction of Na+ permeation of HP RBC by loop diuretics may be of help in experimentally distinguishing HP from LP phenotypes. This information may be crucial in unraveling the structural basis of intrinsic differences in cell membrane Na+ permeability and their possible relationship to essential hypertension.
22Na+流入人红细胞（RBC）的速率因供血者不同而有很大差异。高流入速率可能与原发性高血压的先天性易感性有关。在北欧人中，我们发现红细胞22Na+流入速率最低（LP）和渗透性最高（HP）的人之间相差三倍（从每升红细胞每小时少于0.15毫摩尔钠到大于0.60毫摩尔钠）。为了进一步确定这些被动膜钠转运中明显的遗传差异的决定因素，我们确定了两组正常的实验室和医院工作人员，他们的红细胞22Na+流入速率有显著差异（超过两倍）。我们发现，髓袢利尿剂呋塞米和布美他尼可使22Na+流入HP红细胞的量减少约50%，但对LP红细胞的影响较小。诸如柠檬酸盐和焦磷酸盐等非渗透性聚阴离子也能特异性地减少22Na+流入HP红细胞，但对LP红细胞无此作用。因此，22Na+过度流入HP红细胞可能是通过一条离散的途径（可能通过“钠/钾/氯协同转运”）发生的，而这条途径在LP红细胞中似乎几乎不存在。HP和LP红细胞之间的差异很可能与红细胞阴离子转运本身的多态性无关。HP和LP红细胞中红细胞阴离子（35SO4(2-)）的转运速率相同，且同样受到呋塞米和（程度较轻的）布美他尼的抑制。此外，红细胞阴离子转运的强效抑制剂DIDS（二异硫氰酸芪二磺酸）对两组红细胞的钠通透性均无影响。尽管如此，髓袢利尿剂对HP红细胞钠通透性的优先降低作用可能有助于在实验中区分HP和LP表型。这些信息对于阐明细胞膜钠通透性内在差异的结构基础及其与原发性高血压的可能关系可能至关重要。
