Impact of androgen-induced oxidative stress on hypertension in male SHR
Impact of androgen-induced oxidative stress on hypertension in male SHR
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DOI：
10.1152/ajpregu.00353.2006
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发表时间：
2007-02-01
影响因子：
2.8
通讯作者：
Reckelhoff, Jane F.
中科院分区：
文献类型：
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作者：
Iliescu, Radu;Cucchiarelli, Valeria E.;Reckelhoff, Jane F.
男性的血压比女性高，雄激素和氧化应激被认为在这种两性异形中起作用。自发性高血压大鼠（SHR）是雄激素和氧化应激介导的高血压的动物模型。因此，本研究旨在验证雄激素在一定程度上通过NADPH氧化酶刺激超氧化物的产生而导致SHR高血压的假设。雄性SHR的阉割降低了15%的血压，并减弱了肾皮质匀浆中基础和nadph刺激的超氧化物的产生。去势雄肾皮质NADPH氧化酶p47（phox）和gp91（phox）亚基的表达明显低于正常雄肾皮质NADPH氧化酶p22（phox）亚基。此外，罗泼酚对NADPH氧化酶的抑制作用使完整雄性SHR的血压降低了15 mmHg，并减少了基础和NADPH刺激的超氧化物产生，但对阉割雄性的血压和超氧化物产生没有影响。这些数据支持了雄激素通过NADPH氧化酶依赖机制引起氧化应激从而增加男性SHR血压的假设。
Men have higher blood pressure than women, and androgens and oxidative stress have been implicated as playing roles in this sexual dimorphism. The spontaneously hypertensive rat (SHR) is an animal model of both androgen- and oxidative stress-mediated hypertension. Therefore, the present studies were performed to test the hypothesis that androgens cause hypertension in SHR in part by stimulating superoxide production via NADPH oxidase. Castration of male SHR reduced blood pressure by 15% and attenuated both basal and NADPH-stimulated superoxide production in kidney cortical homogenates. Expression of p47(phox) and gp91(phox) but not p22(phox) subunits of NADPH oxidase were significantly lower in kidney cortex from castrated males compared with intact males. Moreover, inhibition of NADPH oxidase with apocynin caused similar to 15 mmHg reduction in blood pressure and reduced basal and NADPH-stimulated superoxide production in intact male SHR, but had no effect on blood pressure or superoxide production in castrated males. These data support the hypothesis that androgens cause oxidative stress and thereby increase blood pressure in male SHR via an NADPH oxidase-dependent mechanism.