Capasso G, Unwin R, Agulian S, Giebisch G
Department of Cellular and Molecular Physiology, Yale University School of Medicine, New Haven, Connecticut 06510-8026.
J Clin Invest. 1991 Aug;88(2):430-7. doi: 10.1172/JCI115322.
We microperfused the loop of Henle (LOH) to assess its contribution to urine acidification in vivo. Under control conditions (Na HCO3- = 13 mM, perfusion rate approximately 17 nl/min-1) net bicarbonate transport (JHCO3-) was unsaturated, flow- and concentration-dependent, and increased linearly until a bicarbonate load of 1,400 pmol.min-1 was reached. Methazolamide (2 x 10(-4) M) reduced JHCO3 by 70%; the amiloride analogue ethylisopropylamiloride (EIPA) (2 x 10(-4) M) reduced JHCO3 by 40%; neither methazolamide nor EIPA affected net water flux (Jv). The H(+)-ATPase inhibitor bafilomycin A1 (10(-5) M) reduced JHCO3 by 20%; the Cl- channel inhibitor 5-nitro-2'-(3-phenylpropylamino)-benzoate (2 x 10(-4) M) and the Cl(-)-base exchange inhibitor diisothiocyanato-2,2'-stilbenedisulfonate (5 x 10(-5) M), had no effect on fractional bicarbonate reabsorption. Bumetanide (10(-6) M) stimulated bicarbonate transport (net and fractional JHCO3-) by 20%, whereas furosemide (10(-4) M) had no effect on bicarbonate reabsorption; both diuretics reduced Jv. In summary: (a) the LOH contributes significantly to urine acidification. It normally reabsorbs an amount equivalent to 15% of filtered bicarbonate; (b) bicarbonate reabsorption is not saturated; (c) Na(+)-H+ exchange and an ATP-dependent proton pump are largely responsible for the bulk of LOH bicarbonate transport.
我们对髓袢进行微灌注，以评估其在体内对尿液酸化的作用。在对照条件下（碳酸氢钠浓度=13 mM，灌注速率约为17 nl/min-1），净碳酸氢盐转运（JHCO3-）不饱和，与流量和浓度相关，并且在达到1400 pmol.min-1的碳酸氢盐负荷之前呈线性增加。甲氨蝶呤（2×10(-4) M）使JHCO3降低70%；氨氯吡脒类似物乙基异丙基氨氯吡脒（EIPA）（2×10(-4) M）使JHCO3降低40%；甲氨蝶呤和EIPA均不影响净水通量（Jv）。H(+)-ATP酶抑制剂巴弗洛霉素A1（10(-5) M）使JHCO3降低20%；Cl-通道抑制剂5-硝基-2'-(3-苯丙基氨基)-苯甲酸酯（2×10(-4) M）和Cl(-)-碱交换抑制剂二异硫氰酸根合-2,2'-二苯乙烯二磺酸盐（5×10(-5) M）对碳酸氢盐重吸收分数无影响。布美他尼（10(-6) M）使碳酸氢盐转运（净JHCO3-和分数JHCO3-）增加20%，而呋塞米（10(-4) M）对碳酸氢盐重吸收无影响；两种利尿剂均降低Jv。总之：（a）髓袢对尿液酸化有显著作用。它通常重吸收相当于滤过碳酸氢盐15%的量；（b）碳酸氢盐重吸收不饱和；（c）Na(+)-H+交换和ATP依赖性质子泵在髓袢碳酸氢盐转运中起主要作用。
