Lopardo Mariano L, Diaz-Sylvester Paula, Amorena Carlos
CESyMA, Escuela de Ciencia y Tecnología, Universidad Nacional de Gral. San Martín, Avenida Gral Paz 5445, Ed. 23, 1650 San Martín, Argentina.
Pflugers Arch. 2007 May;454(2):289-95. doi: 10.1007/s00424-006-0198-7. Epub 2007 Jan 12.
As consequence of glomerular filtration the viscosity of blood flowing through the efferent arteriole increases. Recently, we found that shear stress modulates proximal bicarbonate reabsorption and nitric oxide (NO.) was the chemical mediator of this effect. In the present work, we found that agonists of NO. production affected basolateral membrane potential (V (blm)) of the proximal convoluted tubule (PCT) epithelium. Using paired micropuncture experiments, we perfused peritubular capillaries with solutions with different viscosity while registering the V (blm). Our results showed that a 50% increment in the viscosity, or the addition of bradykinin (10(-5) M) to the peritubular perfusion solution, induced a significant and similar hyperpolarization of the V (blm) at the PCT epithelium of 6 +/- 0.7 mV (p < 0.05). Both hyperpolarizations were reverted by L-NAME (10(-4) M). Addition of 2,2'-(hydroxynitrosohydrazino) bis-ethanamine (NOC-18) 3 x 10(-4) M to the peritubular perfusion solution induced a hyperpolarization of the same magnitude of that high viscosity or bradykinin. These results strongly suggest the involvement of NO. in the effect of high viscosity solutions. This effect seems to be mediated by activation of K+(ATP) channels as glybenclamide (5 x 10(-5) M) added to peritubular solutions induced a larger depolarization of the V (blm) with high viscosity solutions. Acetazolamide (5 x 10(-5) M) added to high viscosity solutions induced a larger hyperpolarization (8 +/- 1 mV; p < 0.05), suggesting that depolarizing current due to HCO(-)3 exit across the basolateral membrane damps the hyperpolarizing effect of high viscosity. Considering that Na(+) and consequently water reabsorption is highly dependent on electrical gradient, the present data suggest that the endothelium of kidney vascular bed interacts in paracrine fashion with the epithelia, affecting V (blm) and thus modulating PCT reabsorption.
由于肾小球滤过，流经出球小动脉的血液粘度增加。最近，我们发现剪切应力可调节近端碳酸氢盐重吸收，一氧化氮（NO.）是这种作用的化学介质。在本研究中，我们发现NO.生成的激动剂会影响近端小管（PCT）上皮细胞的基底外侧膜电位（V(blm)）。我们通过配对微穿刺实验，在记录V(blm)的同时，用不同粘度的溶液灌注肾小管周围毛细血管。我们的结果表明，粘度增加50%，或在肾小管周围灌注液中添加缓激肽（10(-5)M），会导致PCT上皮细胞的V(blm)出现显著且相似的超极化，幅度为6±0.7mV（p<0.05）。两种超极化均被L-NAME（10(-4)M）逆转。向肾小管周围灌注液中添加3×10(-4)M的2,2'-（羟基亚硝基肼基）双乙胺（NOC-18）会导致与高粘度或缓激肽相同幅度的超极化。这些结果强烈表明NO.参与了高粘度溶液的作用。这种作用似乎是由K+(ATP)通道的激活介导的，因为添加到肾小管周围溶液中的格列本脲（5×10(-5)M）会使高粘度溶液引起的V(blm)出现更大的去极化。添加到高粘度溶液中的乙酰唑胺（5×10(-5)M）会导致更大的超极化（8±1mV；p<0.05），这表明由于HCO(-)3跨基底外侧膜流出而产生的去极化电流会减弱高粘度的超极化作用。考虑到Na(+)以及因此水的重吸收高度依赖于电势梯度，目前的数据表明肾血管床的内皮细胞以旁分泌方式与上皮细胞相互作用，影响V(blm)，从而调节PCT重吸收。
