Morduchowicz G A, Sheikh-Hamad D, Jo O D, Nord E P, Lee D B, Yanagawa N
Service, Veterans Administration Sepulveda Hospital, California.
Kidney Int. 1989 Oct;36(4):576-81. doi: 10.1038/ki.1989.233.
Defect in renal salt excretion may play an important role in the pathogenesis of hypertension. We examined sodium (Na+) uptake by brush border membrane (BBM) vesicles of young (6 week old) spontaneously hypertensive rats (SHR) and normotensive Wistar-Kyoto rats (WKY) of the same age. SHR had lower urinary Na+ excretion (223.1 +/- 9.3 vs. 266.3 +/- 3.7 microEq/day/100 g, N = 8, P less than 0.01) and higher systolic blood pressure (98.9 +/- 1.2 vs. 82.9 +/- 1.8 mm Hg, N = 8, P less than 0.01) than WKY. BBM vesicle Na+ uptake, measured by rapid filtration technique, was higher in SHR when compared to WKY (1.44 +/- 0.03 vs. 1.01 +/- 0.06 nmol/mg/5 sec, N = 4, P less than 0.01). This increase in Na+ influx was apparent only in the present of an outward-directed proton (H+) gradient and was abolished by 1 mM amiloride. BBM permeability to H+ as assessed by acridine orange quenching was not different between SHR and WKY. Kinetic analyses of the amiloride-sensitive BBM Na+ uptake revealed a higher Vmax (2.13 +/- 0.27 vs. 0.70 +/- 0.30 nmol/mg/5 sec, N = 4, P less than 0.01) and a higher km for Na+ (3.55 +/- 0.32 vs. 1.23 +/- 0.14 mM, N = 4, P less than 0.05) in SHR. These findings thus demonstrate an intrinsic derangement in BBM Na+ transport in young SHR which is characterized by increased Na+/H+ antiport activity. This alteration in antiport activity is not attributable to changes in membrane permeability to H+, and is characterized by higher Vmax and km.(ABSTRACT TRUNCATED AT 250 WORDS)
肾盐排泄缺陷可能在高血压发病机制中起重要作用。我们检测了年轻（6周龄）自发性高血压大鼠（SHR）和同龄正常血压Wistar-Kyoto大鼠（WKY）刷状缘膜（BBM）囊泡对钠（Na+）的摄取。与WKY相比，SHR的尿Na+排泄较低（223.1±9.3对266.3±3.7微当量/天/100克，N = 8，P<0.01），收缩压较高（98.9±1.2对82.9±1.8毫米汞柱，N = 8，P<0.01）。通过快速过滤技术测量，SHR的BBM囊泡Na+摄取高于WKY（1.44±0.03对1.01±0.06纳摩尔/毫克/5秒，N = 4，P<0.01）。Na+内流的增加仅在存在外向质子（H+）梯度时明显，并被1毫摩尔氨氯地平消除。通过吖啶橙淬灭评估的BBM对H+的通透性在SHR和WKY之间没有差异。对氨氯地平敏感的BBM Na+摄取的动力学分析显示，SHR的Vmax较高（2.13±0.27对0.70±0.30纳摩尔/毫克/5秒，N = 4，P<0.01），Na+的km较高（3.55±0.32对1.23±0.14毫摩尔，N = 4，P<0.05）。因此，这些发现证明了年轻SHR中BBM Na+转运存在内在紊乱，其特征是Na+/H+反向转运活性增加。反向转运活性的这种改变不归因于膜对H+通透性的变化，其特征是较高的Vmax和km。（摘要截断于250字）
