Angiotensin (1-7) receptor antagonism equalizes angiotensin II-induced hypertension in male and female spontaneously hypertensive rats.
Angiotensin (1-7) receptor antagonism equalizes angiotensin II-induced hypertension in male and female spontaneously hypertensive rats.
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DOI：
10.1161/hypertensionaha.110.153668
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发表时间：
2010-10
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影响因子：
--
通讯作者：
Elmarakby AA
中科院分区：
文献类型：
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作者：
Sullivan JC;Bhatia K;Yamamoto T;Elmarakby AA
与男性相比，女性对血管紧张素 II 的高血压作用不太敏感，但其分子机制尚不清楚。我们假设雄性和雌性自发性高血压大鼠肾皮质中血管紧张素 II、Ang (1-7)、AT1、AT2 和 mas 水平的差异激活导致血管紧张素 II 输注血压反应的性别差异。输注血管紧张素 II 后，男性血压升高幅度高于女性（男性：150±2 至 186±3 mmHg；女性：137±3 至 160±4 mmHg；p<0.05）。血管紧张素 II 输注导致两性血浆和肾皮质血管紧张素 II 水平相当的增加。与雄性大鼠相比，雌性大鼠在基础条件下（195±10 与 67±11 ng/克皮质，p<0.05）和血管紧张素 II 输注后（281±25 与 205±47 ng/克皮质，p<0.05）肾皮质 Ang (1-7) 水平较高。在雄性大鼠的肾皮质中，血管紧张素 II 输注降低了 AT1 蛋白的表达，增加了 AT2 的表达，但 mas 的表达没有变化。在雌性大鼠中，血管紧张素 II 输注后 mas 受体蛋白表达增加，尽管 AT1 和 AT2 表达没有变化。然后，在血管紧张素 II 不存在和存在的情况下，用 Ang (1-7) mas 受体拮抗剂 A-779 治疗雄性和雌性大鼠。 A-779 平衡了男性和女性对血管紧张素 II 的血压反应（治疗结束时的血压：男性，166±4；女性，164±5 mmHg）。总之，Ang (1-7) 导致血管紧张素 II 诱导的自发性高血压大鼠血压升高存在性别差异。
Females are less sensitive to the hypertensive effects of angiotensin II compared to males, although the molecular mechanisms responsible are unknown. We hypothesize that differential activation of angiotensin II, Ang (1–7), AT1, AT2, and mas levels in the renal cortex of male and female spontaneously hypertensive rats contribute to sex differences in the blood pressure response to angiotensin II infusion. Males had a greater increase in blood pressure following angiotensin II infusion than females (males: 150±2 to 186±3 mmHg; females: 137±3 to 160±4 mmHg; p<0.05). Angiotensin II infusion resulted in comparable increases in plasma and renal cortical angiotensin II levels in both sexes. Renal cortical Ang (1–7) levels were higher in female rats under basal conditions (195±10 vs. 67±11 ng/gram cortex, p<0.05) and following angiotensin II infusion (281±25 vs. 205±47 ng/gram cortex, p<0.05) compared to male rats. In the renal cortex of male rats, angiotensin II infusion decreased AT1 protein expression and increased AT2 expression with no change in mas expression. In female rats there was an increase in mas receptor protein expression with angiotensin II infusion although AT1 and AT2 expression were unchanged. Male and female rats were then treated with the Ang (1–7) mas receptor antagonist, A-779, in the absence and presence of angiotensin II. A-779 equalized the blood pressure response to angiotensin II in males and females (blood pressure at the end of treatment: males, 166±4; females, 164±5 mmHg). In conclusion, Ang (1–7) contributes to the sex difference in angiotensin II-induced increases in blood pressure in spontaneously hypertensive rats.