Colombero Cecilia, Venara Marcela, Gonzalez Daniel, Roman Richard J, Nowicki Susana
Centro de Investigaciones Endocrinológicas "Dr. César Bergadá" (CEDIE), CONICET - FEI - División de Endocrinología, Hospital de Niños Ricardo Gutiérrez, Buenos Aires, Argentina.
Department of Pharmacology and Toxicology, The University of Mississippi Medical Center, Jackson, Mississippi.
Physiol Rep. 2014 Jun 11;2(6). doi: 10.14814/phy2.12040. Print 2014 Jun 1.
Thyroidectomy augments the natriuretic response to volume expansion; however, the mechanism remains unknown. This study assessed the role of 20-hydroxyeicosatetraenoic acid (20-HETE) in the natriuretic response to an acute volume expansion in hypothyroid rats. Urine flow (1.9-fold), sodium excretion (2.4-fold), fractional sodium excretion (3.8-fold), and distal delivery of sodium (4.1-fold) increased to a greater extent in thyroidectomized rats (TX) than in sham-operated controls (SHAM) following i.v. infusion of isotonic saline (5% body weight) over 60 min. This was associated with inhibition of both proximal and distal tubular reabsorption of sodium. Administration of two mechanistic and chemical dissimilar inhibitors of the synthesis of 20-HETE, 1-aminobenzotriazole (ABT), and N-hydroxy-N'-(-4-butyl-2-methylphenyl)formamidine (HET0016) decreased the natriuretic response in TX rats. Glomerular filtration rate was lower in TX than in SHAM rats and was not altered by the CYP4A inhibitors. The expression, intrarenal distribution, and the formation of 20-HETE and expoxygenase metabolites of arachidonic acid were similar in the cortex and medulla of SHAM and TX rats. These results suggest that CYP4A-derived metabolites of arachidonic acid play an important role in the enhanced natriuretic response to volume expansion in hypothyroid rats even though TX did not alter the expression or activity of these enzymes.
甲状腺切除术增强了对容量扩张的利钠反应；然而，其机制仍不清楚。本研究评估了20-羟基二十碳四烯酸（20-HETE）在甲状腺功能减退大鼠对急性容量扩张的利钠反应中的作用。在静脉输注等渗盐水（5%体重）60分钟后，甲状腺切除大鼠（TX）的尿流量（1.9倍）、钠排泄量（2.4倍）、钠排泄分数（3.8倍）和远端钠输送量（4.1倍）比假手术对照组（SHAM）增加的程度更大。这与近端和远端肾小管对钠重吸收的抑制有关。给予两种机制和化学性质不同的20-HETE合成抑制剂，1-氨基苯并三唑（ABT）和N-羟基-N'-（-4-丁基-2-甲基苯基）甲脒（HET0016），可降低TX大鼠的利钠反应。TX大鼠的肾小球滤过率低于SHAM大鼠，且不受CYP4A抑制剂的影响。SHAM和TX大鼠皮质和髓质中20-HETE和花生四烯酸环氧合酶代谢产物的表达、肾内分布及生成相似。这些结果表明，尽管甲状腺切除术未改变花生四烯酸CYP4A衍生代谢产物的表达或活性，但它们在甲状腺功能减退大鼠对容量扩张增强的利钠反应中起重要作用。
