Background:Emerging evidence over the past several years suggests that diurnal control of sodium excretion is sex dependent and involves the renal endothelin system. Given recent awareness of disruptions of circadian function in obesity, we determined whether diet-induced obesity impairs renal handling of an acute salt load at different times of day and whether this varies by sex and is associated with renal endothelin dysfunction.Methods:Male and female Sprague-Dawley rats were placed on a high-fat diet for 8 weeks before assessing renal sodium handling and blood pressure.Results:Male, but not female, rats on high fat had a significantly reduced natriuretic response to acute NaCl injection at the beginning of their active period that was associated with lower endothelin 1 (ET-1) excretion, lower ET-1 mRNA expression in the cortex and outer medulla as well as lower ET_B receptor expression in the outer medulla of the high-fat rats. Obese males also had significantly higher blood pressure (telemetry) that was exacerbated by adding high salt to the diet during the last 2 weeks. While female rats developed hypertension with a high-fat diet, they were not salt sensitive and ET-1 excretion was unchanged.Conclusions:These data identify diet-induced obesity as a sex-specific disruptive factor for maintaining proper sodium handling. Although high-fat diets induce hypertension in both sexes, these data reveal that males are at greater risk of salt-dependent hypertension and further suggest that females have more redundant systems that can be productive against salt-sensitive hypertension in at least some circumstances.

中文翻译：

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饮食引起的肥胖大鼠每日钠处理的性别差异

背景：过去几年的新证据表明，钠排泄的昼夜控制具有性别依赖性，并且涉及肾内皮素系统。鉴于最近人们意识到肥胖会破坏昼夜节律功能，我们确定了饮食引起的肥胖是否会损害肾脏在一天中不同时间处理急性盐负荷的能力，以及这种情况是否因性别而异并与肾内皮素功能障碍有关。方法：男性和女性在评估肾钠处理和血压之前，将 Sprague-Dawley 大鼠置于高脂饮食 8 周。 结果：雄性（而非雌性）高脂大鼠在实验开始时对急性 NaCl 注射的利尿钠反应显着降低。它们的活跃期与内皮素 1 (ET-1) 排泄较低相关，高脂大鼠髓质外层_{B受体的表达。}肥胖男性的血压也显着升高（遥测），过去两周在饮食中添加高盐会加剧这种情况。虽然雌性大鼠因高脂肪饮食而患上高血压，但它们对盐不敏感，且 ET-1 排泄也没有变化。 结论：这些数据表明饮食引起的肥胖是维持适当钠处理的性别特异性破坏因素。尽管高脂肪饮食会诱发男女高血压，但这些数据表明，男性患盐依赖性高血压的风险更大，并进一步表明女性拥有更多的冗余系统，至少在某些情况下可以有效对抗盐敏感性高血压。