SEX-DIFFERENCES RESULT IN INCREASED MORBIDITY FROM HYPONATREMIA IN FEMALE RATS
SEX-DIFFERENCES RESULT IN INCREASED MORBIDITY FROM HYPONATREMIA IN FEMALE RATS
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DOI：
10.1152/ajpregu.1989.256.4.r880
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发表时间：
1989-04-01
影响因子：
--
通讯作者：
NORMAN, D
中科院分区：
文献类型：
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作者：
FRASER, CL;KUCHARCZYK, J;NORMAN, D
在其他健康的年轻女性中出现症状性低钠血症可导致死亡或永久性脑损伤。然而，女性对低钠血症并发症的易感性增加的原因尚不清楚。为了确定通常保护大脑免受低钠血症损害的机制是否在女性中不如男性有效，我们研究了低钠血症雄性和雌性大鼠脑中的钠转运以及注射精氨酸加压素对脑高能磷酸盐代谢和细胞内pH的影响。雌性大鼠全脑突触体的基础钠摄取（2.20 nmol/mg蛋白质）和雄性（2.98 nmol/mg蛋白质）无统计学差异。相反，在雌性脑中，藜芦碱刺激的钠摄取为8.20 nmol/mg蛋白，比雄性脑中观察到的6.12 nmol/mg蛋白高86%（P < 0.001）。此外，女性在5 - 60 s之间的钠摄取量显著高于男性（P < 0.001）。这些数据表明，Na+-K+-腺苷三磷酸酶（ATP酶）泵功能在雌性大鼠脑突触体是有效的比男性。为了确定精氨酸加压素（一种促进肾脏水潴留的肽类激素）是否对大脑能量代谢有任何影响，我们对正常钠血症的年轻成年雄性和雌性大鼠的大脑进行了磷-31（31 P）磁共振波谱（MRS）研究，这些大鼠接受了高（20 IU）外周剂量的精氨酸加压素。我们发现，降低高能磷酸盐的产生，升高无机磷酸盐，和细胞内酸中毒后，精氨酸加压素管理的女性，但男性。精氨酸加压素注射后90分钟，7只加压素治疗的雌性大鼠中有5只死亡，而所有6只雄性大鼠脑磷代谢正常并存活。Na+-K+-ATP酶泵功能下降以及ATP和磷酸肌酸产生下降的综合作用表明，雌性大鼠大脑防御低钠血症诱导的脑水肿的能力明显受损，这通常与血浆加压素水平升高有关。
The development of symptomatic hyponatremia in otherwise healthy young women can result in death or permanent brain damage. The reasons for the increased female susceptibility to complications from hyponatremia are, however, unclear. To determine whether mechanisms that normally defend the brain against damage from hyponatremia are less effective in females than males, we studied both sodium transport in the brains of hyponatremic male and female rats and the effects of parenteral arginine vasopressin on brain high-energy phosphate metabolism and intracellular pH. Basal sodium uptake in synaptosomes prepared from whole brain of females (2.20 nmol/mg protein) and males (2.98 nmol/mg protein) was not statistically different. In contrast, veratridine-stimulated sodium uptake in female brain was 8.20 nmol/mg protein, which was 86% greater (P < 0.001) than the 6.12 nmol/mg protein observed for male brain. Additionally, sodium uptake between 5 and 60 s was significantly (P < 0.001) greater in females than in males. These data suggest that the Na+-K+-adenosinetriphosphatase (ATPase) pump function in female rat brain synpatosomes is less effective than in males. To determine whether argine vasopressin, a peptide hormone that promotes water retention by the kidney, had any effects on cerebral energy metabolism, we performed phosphorus-31 (31P) magnetic resonance spectroscopy (MRS) studies on the brain of normonatremic young adult male and female rats subjected to high (20 IU) peripheral doses of arginine vasopressin. We found decreased high-energy phosphate generation, elevated inorganic phosphate, and intracellular acidosis after arginine vasopressin administration in females but not males. Ninety minutes after arginine vasopressin injections, five of seven vasopressin-treated female rats had died, whereas all six males had normal cerebral phosphorus metabolism and survived. The combined effects of decreased Na+-K+-ATPase pump function and decreased ATP and phosphocreatine production suggest a marked impairment in the ability of the female rat brain to defend against hyponatremia-induced cerebral edema that is often associated with elevated plasma vasopressin levels.