Sex- and age-related differences in the chronic pressure-natriuresis relationship: role of the angiotensin type 2 receptor
Sex- and age-related differences in the chronic pressure-natriuresis relationship: role of the angiotensin type 2 receptor
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DOI：
10.1152/ajprenal.00288.2014
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发表时间：
2014-10-15
影响因子：
4.2
通讯作者：
Denton, Kate M.
中科院分区：
文献类型：
--
作者：
Mirabito, Katrina M.;Hilliard, Lucinda M.;Denton, Kate M.
性激素调节肾素-血管紧张素系统。例如，雌激素增强血管紧张素2型受体的表达。我们假设，与男性相比，血管紧张素2型受体的激活改变了女性的慢性压力-尿钠排泄关系，并且这种作用随着年龄的增长而消失。通过无线电遥测测量成年（4月龄）和老年（14月龄）野生型和血管紧张素2型受体敲除雄性和雌性小鼠的平均动脉压。慢性压力-尿钠排泄曲线构建，同时小鼠维持正常盐（0.26%）饮食和高盐（5.0%）饮食6天。成年野生型雌性的平均动脉压低于雄性（分别为88 +/- 1和97 +/- 1 mmHg），这种差异随着年龄的增长而保持，但在成年敲除小鼠中不存在。在野生型雌性中，慢性压力-尿钠排泄关系与基因敲除雌性相比发生了显著变化，这种影响随着年龄的增长而消失。在男性中，慢性压力-尿钠排泄关系不受血管紧张素2型受体缺乏的影响。与年龄匹配的雌性小鼠相比，雄性小鼠的慢性压力-尿钠排泄关系发生了显著变化。肾血管紧张素2型受体的表达是四倍以上的成年野生型女性比男性。随着年龄的增长，女性血管紧张素2型受体与血管紧张素1型受体的平衡降低。相反，在男性中，血管紧张素受体的表达并没有随着年龄的显着变化。总之，血管紧张素2型受体以年龄和性别依赖的方式调节慢性压力-尿钠排泄关系。
Sex hormones regulate the renin-angiotensin system. For example, estrogen enhances expression of the angiotensin type 2 receptor. We hypothesized that activation of the angiotensin type 2 receptor shifts the chronic pressure-natriuresis relationship leftward in females compared with males and that this effect is lost with age. Mean arterial pressure was measured by radiotelemetry in adult (4 mo old) and aged (14 mo old) wild-type and angiotensin type 2 receptor knockout male and female mice. Chronic pressure-natriuresis curves were constructed while mice were maintained on a normal-salt (0.26%) diet and following 6 days of high salt (5.0%) diet. Mean arterial pressure was lower in adult wild-type females than males (88 +/- 1 and 97 +/- 1 mmHg, respectively), a difference that was maintained with age, but was absent in adult knockout mice. In wild-type females, the chronic pressure-natriuresis relationship was shifted leftward compared with knockout females, an effect that was lost with age. In males, the chronic pressure-natriuresis relationship was not influenced by angiotensin type 2 receptor deficiency. Compared with age-matched females, the chronic pressure-natriuresis relationships in male mice were shifted rightward. Renal expression of the angiotensin type 2 receptor was fourfold greater in adult wild-type females than males. With age, the angiotensin type 2 receptor-to-angiotensin type 1 receptor balance was reduced in females. Conversely, in males, angiotensin receptor expression did not vary significantly with age. In conclusion, the angiotensin type 2 receptor modulates the chronic pressure-natriuresis relationship in an age- and sex-dependent manner.