INTRODUCTION Hyponatremia due to elevated arginine vasopressin (AVP) secretion increases mortality in liver failure patients. No previous studies have addressed sex differences in hyponatremia in liver failure animal models. OBJECTIVE This study addressed this gap in our understanding of the potential sex differences in hyponatremia associated with increased AVP secretion. METHODS This study tested the role of sex in the development of hyponatremia using adult male, female, and ovariectomized (OVX) female bile duct-ligated (BDL) rats. RESULTS All BDL rats had significantly increased liver to body weight ratios compared to sham controls. Male BDL rats had hyponatremia with significant increases in plasma copeptin and FosB expression in supraoptic AVP neurons compared to male shams (all p < 0.05; 5-7). Female BDL rats did not become hyponatremic or demonstrate increased supraoptic AVP neuron activation and copeptin secretion compared to female shams. Plasma oxytocin was significantly higher in female BDL rats compared to female sham (p < 0.05; 6-10). This increase was not observed in male BDL rats. Ovariectomy significantly decreased plasma estradiol in sham rats compared to intact female sham (p < 0.05; 6-10). However, circulating estradiol was significantly elevated in OVX BDL rats compared to the OVX and female shams (p < 0.05; 6-10). Adrenal estradiol, testosterone, and dehydroepiandrosterone (DHEA) were measured to identify a possible source of circulating estradiol in OVX BDL rats. The OVX BDL rats had significantly increased adrenal estradiol along with significantly decreased adrenal testosterone and DHEA compared to OVX shams (all p < 0.05; 6-7). Plasma osmolality, hematocrit, copeptin, and AVP neuron activation were not significantly different between OVX BDL and OVX shams. Plasma oxytocin was significantly higher in OVX BDL rats compared to OVX sham. CONCLUSIONS Our results show that unlike male BDL rats, female and OVX BDL rats did not develop hyponatremia, supraoptic AVP neuron activation, or increased copeptin secretion compared to female shams. Adrenal estradiol might have compensated for the lack of ovarian estrogens in OVX BDL rats.

中文翻译：

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胆管结扎大鼠加压素和催产素分泌调节的性别差异。


简介 精氨酸加压素 (AVP) 分泌升高导致的低钠血症会增加肝衰竭患者的死亡率。之前没有研究探讨肝衰竭动物模型中低钠血症的性别差异。目的 这项研究解决了我们对低钠血症与 AVP 分泌增加相关的潜在性别差异的理解上的差距。方法 本研究使用成年雄性、雌性和卵巢切除 (OVX) 雌性胆管结扎 (BDL) 大鼠测试了性别在低钠血症发生中的作用。结果 与假手术对照组相比，所有 BDL 大鼠的肝脏与体重之比均显着增加。与雄性假手术组相比，雄性 BDL 大鼠患有低钠血症，血浆和肽素和视上 AVP 神经元中 FosB 的表达显着增加（所有 p < 0.05；5-7）。与雌性假手术组相比，雌性 BDL 大鼠没有出现低钠血症，也没有表现出视上 AVP 神经元激活和和肽素分泌增加。与雌性假手术大鼠相比，雌性 BDL 大鼠的血浆催产素显着较高（p < 0.05；6-10）。在雄性 BDL 大鼠中未观察到这种增加。与完整的雌性假手术大鼠相比，卵巢切除术显着降低了假手术大鼠的血浆雌二醇（p < 0.05；6-10）。然而，与 OVX 和雌性假手术组大鼠相比，OVX BDL 大鼠的循环雌二醇显着升高（p < 0.05；6-10）。测量肾上腺雌二醇、睾酮和脱氢表雄酮 (DHEA)，以确定 OVX BDL 大鼠循环雌二醇的可能来源。与 OVX 假手术组相比，OVX BDL 大鼠的肾上腺雌二醇显着增加，同时肾上腺睾酮和 DHEA 显着降低（所有 p < 0.05；6-7）。 OVX BDL 和 OVX 假手术之间的血浆渗透压、血细胞比容、和肽素和 AVP 神经元激活没有显着差异。与 OVX 假手术大鼠相比，OVX BDL 大鼠的血浆催产素显着较高。结论 我们的结果表明，与雄性 BDL 大鼠不同，与雌性假鼠相比，雌性和 OVX BDL 大鼠没有出现低钠血症、视上 AVP 神经元激活或和肽素分泌增加。肾上腺雌二醇可能补偿了 OVX BDL 大鼠卵巢雌激素的缺乏。