Male gender increases sensitivity to renal injury in response to cholesterol loading
Male gender increases sensitivity to renal injury in response to cholesterol loading
复制标题
DOI：
10.1152/ajprenal.00009.2002
复制
发表时间：
2003-04-01
影响因子：
4.2
通讯作者：
Joles, JA
中科院分区：
文献类型：
--
作者：
Attia, DM;Goldschmeding, R;Joles, JA
男性肾损伤的风险高于女性。这可能与一氧化氮（NO）的可用性有关，因为雌性大鼠具有较高的肾内皮NO合酶（NOS）水平。此前，我们的实验室发现，与雌性大鼠相比，雄性大鼠对NOS抑制诱导的蛋白尿更敏感。血脂异常和高胆固醇血症剂量依赖性地降低肾NOS活性，并造成肾损伤。我们推测，暴露于高胆固醇血症的雄性大鼠会导致更多的肾损伤比雌性大鼠由于先验较低的肾脏NO系统。雌性和雄性大鼠喂饲无胆固醇、低剂量胆固醇和高剂量胆固醇24周。胆固醇喂养剂量依赖性地增加雌性和雄性大鼠的蛋白尿，但雄性大鼠在相似的血浆胆固醇下发生更多的蛋白尿（P < 0.001）。对照组雄性动物的肾NOS活性低于对照组雌性动物（4.44 +/- 0.18 vs.7.46 +/- 0.37 pmol.min（-1）.mg protein（-1）; P < 0.05），胆固醇喂养降低了雄性和雌性动物的肾NOS活性（P < 0.05）。胆固醇喂养的男性显着更多的血管，肾小球，和tubulointerstitial单核细胞/巨噬细胞流入和损伤比女性。因此，在基线条件下，雄性大鼠肾脏NOS活性低于雌性大鼠。这可能解释了为什么雄性大鼠对降低NO可用性的因素（例如高胆固醇血症）造成的肾损伤更敏感。
Males are at greater risk for renal injury than females. This may relate to nitric oxide (NO) availability, because female rats have higher renal endothelial NO synthase (NOS) levels. Previously, our laboratory found susceptibility to proteinuria induced by NOS inhibition in male compared with female rats. Dyslipidemia and hypercholesterolemia dose dependently decreased renal NOS activity and caused renal injury in female rats. We hypothesized that exposure of male rats to hypercholesterolemia would lead to more renal injury in male than in female rats due to an a priori lower renal NO system. Female and male rats were fed no, low-dose, or high-dose cholesterol for 24 wk. Cholesterol feeding dose dependently increased proteinuria in both female and male rats, but male rats developed more proteinuria at similar plasma cholesterol (P < 0.001). Control males had lower renal NOS activity than control females (4.44 +/- 0.18 vs. 7.46 +/- 0.37 pmol.min(-1).mg protein(-1); P < 0.05), and cholesterol feeding decreased renal NOS activity in males and in females (P < 0.05). Cholesterol-fed males developed significantly more vascular, glomerular, and tubulointerstitial monocyte/macrophage influx and injury than females. Thus under baseline conditions, male rats have lower renal NOS activity than female rats. This may explain why male rats are more sensitive to renal injury by factors that decrease NO availability, such as hypercholesterolemia.