Nagami Glenn T
Nephrology Section, Medical Research Services, Veterans Affairs Greater Los Angeles Healthcare System, Los Angeles, CA 90073, USA.
Am J Physiol Renal Physiol. 2004 Oct;287(4):F707-12. doi: 10.1152/ajprenal.00189.2003.
ANG II has potent effects on ammonia production and secretion rates by the proximal tubule and is found in substantial concentrations in the lumen of the proximal tubule in vivo. Because our previous studies demonstrated that acid loading enhanced the stimulatory effects of ANG II on ammonia production and secretion by S2 proximal tubule segments, we examined the effect of ANG II on ammonia production and secretion by isolated, perfused S3 segments from nonacidotic control mice and acidotic mice given NH4Cl for 7 days. In the absence of ANG II, ammonia production and secretion rates were no different in S3 segments from acidotic and control mice. By contrast, when ANG II was present in the luminal perfusion solution, ammonia production and secretion rates were stimulated, in a losartan-inhibitable manner, to a greater extent in S3 segments from acidotic mice. Ammonia secretion rates in S3 segments were largely inhibited by perfusion with a low-sodium solution containing amiloride in the presence or absence of ANG II. These results demonstrated that isolated, perfused mouse S3 proximal tubule segments produce and secrete ammonia, that NH4Cl-induced acidosis does not affect the basal rates of ammonia production and secretion, and that ANG II, added to the luminal fluid, stimulates ammonia production and secretion to a greater extent in S3 segments from acidotic mice. These findings suggest that S3 segments, in the presence of ANG II, can contribute to the enhanced renal excretion that occurs with acid loading.
血管紧张素II（ANG II）对近端小管的氨生成和分泌速率有显著影响，且在体内近端小管管腔中浓度较高。由于我们之前的研究表明，酸负荷增强了ANG II对S2近端小管节段氨生成和分泌的刺激作用，因此我们研究了ANG II对来自非酸中毒对照小鼠和给予氯化铵7天的酸中毒小鼠的分离灌注S3节段氨生成和分泌的影响。在没有ANG II的情况下，酸中毒小鼠和对照小鼠的S3节段氨生成和分泌速率没有差异。相比之下，当管腔灌注液中存在ANG II时，酸中毒小鼠的S3节段氨生成和分泌速率以氯沙坦可抑制的方式受到更大程度的刺激。在有或没有ANG II的情况下，用含阿米洛利的低钠溶液灌注可大大抑制S3节段的氨分泌速率。这些结果表明，分离灌注的小鼠S3近端小管节段能产生和分泌氨，氯化铵诱导的酸中毒不影响氨生成和分泌的基础速率，并且添加到管腔液中的ANG II在酸中毒小鼠的S3节段中能更大程度地刺激氨生成和分泌。这些发现表明，在ANG II存在的情况下，S3节段可能有助于酸负荷时增强的肾脏排泄。
