Iliescu Radu, Cucchiarelli Valeria E, Yanes Licy L, Iles Joshua W, Reckelhoff Jane F
Department of Physiology and Biophysics, The Center for Excellence in Cardiovascular-Renal Research, University of Mississippi Medical Center, 2500 N. State St., Jackson, MS 39216-4505, USA.
Am J Physiol Regul Integr Comp Physiol. 2007 Feb;292(2):R731-5. doi: 10.1152/ajpregu.00353.2006. Epub 2006 Jul 20.
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 approximately 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.
男性的血压高于女性，雄激素和氧化应激被认为在这种性别差异中起作用。自发性高血压大鼠（SHR）是雄激素和氧化应激介导的高血压动物模型。因此，本研究旨在验证以下假设：雄激素通过刺激NADPH氧化酶产生超氧化物，部分导致SHR高血压。雄性SHR去势后血压降低15%，并减弱了肾皮质匀浆中基础和NADPH刺激的超氧化物产生。与完整雄性相比，去势雄性肾皮质中NADPH氧化酶的p47（phox）和gp91（phox）亚基而非p22（phox）亚基的表达显著降低。此外，用阿朴吗啡抑制NADPH氧化酶可使完整雄性SHR的血压降低约15 mmHg，并减少基础和NADPH刺激的超氧化物产生，但对去势雄性的血压或超氧化物产生没有影响。这些数据支持以下假设：雄激素导致氧化应激，从而通过NADPH氧化酶依赖性机制增加雄性SHR的血压。
