Batlle D C, Sharma A M, Alsheikha M W, Sobrero M, Saleh A, Gutterman C
Department of Medicine, Northwestern University Medical School, Chicago, Illinois 60611-3008.
J Clin Invest. 1993 May;91(5):2178-84. doi: 10.1172/JCI116444.
Acid-base status and renal acid excretion were studied in the Dahl/Rapp salt-sensitive (S) rat and its genetically salt-resistant counterpart (R). S rats developed hypertension while on a very high salt diet (8%) and while on a more physiological salt diet (1%) and remained normotensive while on a very low salt diet (0.08%). Under the high salt diet, intracellular pH measured in freshly isolated thymic lymphocytes using 2',7'-bis (carboxyethyl)-5 (6)-carboxyfluorescein acetomethyl ester, a pH-sensitive dye, was lower in S than in R rats both when measured in the presence of HCO3/CO2 (7.32 +/- 0.02 vs. 7.38 +/- 0.02, respectively, P < 0.05) and in its absence (7.18 +/- 0.04 vs. 7.27 +/- 0.02, respectively, P < 0.05). Under the high salt diet, net acid excretion was higher in S than R rats (1,777 +/- 111 vs. 1,017 +/- 73 muEq/24 h per 100 g body wt, respectively, P < 0.001), and this difference was due to higher rates of both titratable acid and ammonium excretion. Directionally similar differences in intracellular pH and net acid excretion between S and R rats were also observed in salt-restricted animals. In S and R rats placed on a normal salt intake (1%) and strictly pair-fed to control food intake as a determinant of dietary acid, net acid excretion was also higher in S than in R rats (562 +/- 27 vs. 329 +/- 21 muEq/24 h per 100 g, respectively, P < 0.01). No significant difference in either blood pH or bicarbonate levels were found between S and R rats on either the 0.08%, 1%, or 8% salt diets. We conclude that renal acid excretion is augmented in the salt-sensitive Dahl/Rapp rat. Enhanced renal acid excretion may be a marker of increased acid production by cells from subjects with salt-sensitive hypertension.
在Dahl/Rapp盐敏感（S）大鼠及其基因抗盐对应物（R）中研究了酸碱状态和肾脏酸排泄。S大鼠在高盐饮食（8%）和更接近生理盐饮食（1%）时会出现高血压，而在低盐饮食（0.08%）时保持血压正常。在高盐饮食下，使用pH敏感染料2',7'-双（羧乙基）-5（6）-羧基荧光素乙酰甲酯在新鲜分离的胸腺淋巴细胞中测量的细胞内pH值，在有HCO3/CO2存在时（分别为7.32±0.02对7.38±0.02，P<0.05）和不存在时（分别为7.18±0.04对7.27±0.02，P<0.05），S大鼠均低于R大鼠。在高盐饮食下，S大鼠的净酸排泄高于R大鼠（分别为每100克体重1777±111对1017±73微当量/24小时，P<0.001），这种差异是由于可滴定酸和铵排泄率均较高。在限盐动物中也观察到S和R大鼠在细胞内pH值和净酸排泄方面存在方向相似的差异。在给予正常盐摄入量（1%）并严格配对喂养以控制食物摄入量作为饮食酸决定因素的S和R大鼠中，S大鼠的净酸排泄也高于R大鼠（分别为每100克562±27对329±21微当量/24小时，P<0.01）。在0.08%、1%或8%盐饮食的S和R大鼠之间，血液pH值或碳酸氢盐水平均未发现显著差异。我们得出结论，盐敏感的Dahl/Rapp大鼠肾脏酸排泄增加。肾脏酸排泄增强可能是盐敏感性高血压患者细胞酸产生增加的一个标志。
