Department of Physiology and Anatomy, University of North Texas Health Science Center at Fort Worth, Fort Worth, Texas, USA.
Department of Pharmaceutical Sciences, School of Pharmacy, University of North Texas Health Science Center at Fort Worth, Fort Worth, Texas, USA.
Neuroendocrinology. 2021;111(3):237-248. doi: 10.1159/000508104. Epub 2020 Apr 24.
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.
This study addressed this gap in our understanding of the potential sex differences in hyponatremia associated with increased AVP secretion.
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.
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.
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.
由于精氨酸血管加压素(AVP)分泌增加导致的低钠血症会增加肝功能衰竭患者的死亡率。以前的研究没有解决肝功能衰竭动物模型中与 AVP 分泌增加相关的低钠血症的性别差异。
本研究旨在探讨性别在与 AVP 分泌增加相关的低钠血症中的潜在性别差异。
本研究使用成年雄性、雌性和去卵巢(OVX)雌性胆管结扎(BDL)大鼠,检测性别在低钠血症发展中的作用。
所有 BDL 大鼠的肝体比与假手术对照组相比均显著增加。与雄性假手术组相比,雄性 BDL 大鼠出现低钠血症,且视上核 AVP 神经元中的 copeptin 和 FosB 表达显著增加(均 P < 0.05;5-7)。与雌性假手术组相比,雌性 BDL 大鼠并未出现低钠血症,也未出现视上核 AVP 神经元激活和 copeptin 分泌增加。与雌性假手术组相比,雌性 BDL 大鼠的血浆催产素显著升高(P < 0.05;6-10)。这种增加在雄性 BDL 大鼠中没有观察到。与完整的雌性假手术组相比,卵巢切除术显著降低了假手术组大鼠的血浆雌二醇(P < 0.05;6-10)。然而,OVX BDL 大鼠的循环雌二醇水平明显高于 OVX 和雌性假手术组(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 大鼠中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著增加,而肾上腺睾酮和 DHEA 显著降低(均 P < 0.05;6-7)。OVX BDL 大鼠与 OVX 假手术组之间的血浆渗透压、红细胞压积、copeptin 和 AVP 神经元激活无显著差异。与 OVX 假手术组相比,OVX BDL 大鼠的血浆催产素显著升高。
与雄性 BDL 大鼠不同,雌性和 OVX BDL 大鼠与雌性假手术组相比,并未出现低钠血症、视上核 AVP 神经元激活或 copeptin 分泌增加。肾上腺雌二醇可能补偿了 OVX BDL 大鼠中卵巢雌激素的缺乏。