Amlal Hassane, Sheriff Sulaiman, Faroqui Somia, Ma Liyun, Barone Sharone, Petrovic Snezana, Soleimani Manoocher
Division of Nephrology and Hypertension, Department of Medicine, University of Cincinnati, Cincinnati, Ohio 45267-0585, USA.
Am J Nephrol. 2006;26(2):194-205. doi: 10.1159/000093305. Epub 2006 May 11.
The objective of these studies was to examine the effects of long-term vasopressin treatment on acid-base transporters in the collecting duct of rat kidney.
Brattleboro rats were placed in metabolic cages and treated with daily injections of 1-desamino-8-D-arginine vasopressin (dDAVP), a selective V2-receptor agonist, or its vehicle (control) for up to 8 days.
dDAVP treatment resulted in a significant reduction in serum bicarbonate concentration, and caused the upregulation of key ammoniagenesis enzymes, along with increased urinary NH4+ excretion. Northern hybridization and immunofluorescence labeling indicated a significant increase (+80%) in mRNA expression of the apical Cl-/HCO3- exchanger pendrin (PDS), along with a sharp increase in its protein abundance in B-type intercalated cells in the cortical collecting duct in dDAVP-treated rats. In the inner medullary collecting duct, the abundance of basolateral Cl-/HCO3- exchanger (AE1) and apical H+-ATPase was significantly reduced in dDAVP-treated rats. Kidney renin mRNA increased significantly and correlated with an increase in serum aldosterone levels in dDAVP-injected rats. Serum corticosterone levels were, however, reduced and correlated with increased mRNA levels of renal 11beta-hydroxysteroid dehydrogenase-2 (11beta-HSD2) and decreased mRNA expression of 11beta-hydroxylase in the adrenal gland of dDAVP-injected rats.
Chronic administration of dDAVP to Brattleboro rats is associated with the upregulation of PDS and downregulation of H+-ATPase and AE1 in the collecting duct, along with increased ammoniagenesis. Stimulation of the renin-angiotensin-aldosterone system and/or decreased glucocorticoid levels likely plays a role in the transduction of these effects.
这些研究的目的是检测长期血管加压素治疗对大鼠肾集合管酸碱转运蛋白的影响。
将布拉特洛维大鼠置于代谢笼中，每日注射选择性V2受体激动剂1-去氨基-8-D-精氨酸血管加压素（dDAVP）或其溶媒（对照），持续8天。
dDAVP治疗导致血清碳酸氢盐浓度显著降低，关键氨生成酶上调，同时尿NH4+排泄增加。Northern杂交和免疫荧光标记显示，dDAVP治疗的大鼠皮质集合管B型闰细胞顶端Cl-/HCO3-交换体pendrin（PDS）的mRNA表达显著增加（+80%），其蛋白丰度急剧增加。在髓质内集合管，dDAVP治疗的大鼠基底外侧Cl-/HCO3-交换体（AE1）和顶端H+-ATP酶的丰度显著降低。注射dDAVP的大鼠肾素mRNA显著增加，并与血清醛固酮水平升高相关。然而，注射dDAVP的大鼠血清皮质酮水平降低，与肾11β-羟基类固醇脱氢酶-2（11β-HSD2）的mRNA水平升高和肾上腺11β-羟化酶的mRNA表达降低相关。
对布拉特洛维大鼠长期给予dDAVP与集合管中PDS上调、H+-ATP酶和AE1下调以及氨生成增加有关。肾素-血管紧张素-醛固酮系统的激活和/或糖皮质激素水平降低可能在这些效应的传导中起作用。
