Xue B, Johnson A K, Hay M
Department of Psychology, University of Iowa, Gainesville, IA 52242, USA.
Braz J Med Biol Res. 2007 May;40(5):727-34. doi: 10.1590/s0100-879x2007000500018.
Sex differences in the development of hypertension and cardiovascular disease have been described in humans and in animal models. In this paper we will review some of our studies which have as their emphasis the examination of the role of sex differences and sex steroids in modulating the central actions of angiotensin II (ANG II) via interactions with free radicals and nitric oxide, generating pathways within brain circumventricular organs and in central sympathomodulatory systems. Our studies indicate that low-dose infusions of ANG II result in hypertension in wild-type male mice but not in intact wild-type females. Furthermore, we have demonstrated that ANG II-induced hypertension in males is blocked by central infusions of the androgen receptor antagonist, flutamide, and by central infusions of the superoxide dismutase mimetic, tempol. We have also found that, in comparison to females, males show greater levels of intracellular reactive oxygen species in circumventricular organ neurons following long-term ANG II infusions. In female mice, ovariectomy, central blockade of estrogen receptors or total knockout of estrogen a receptors augments the pressor effects of ANG II. Finally, in females but not in males, central blockade of nitric oxide synthase increases the pressor effects of ANG II. Taken together, these results suggest that sex differences and estrogen and testosterone play important roles in the development of ANG II-induced hypertension.
高血压和心血管疾病的发展过程中存在性别差异，这在人类和动物模型中均有描述。在本文中，我们将回顾一些我们的研究，这些研究重点考察了性别差异和性类固醇通过与自由基和一氧化氮相互作用，在调节血管紧张素II（ANG II）的中枢作用方面所起的作用，这些相互作用发生在脑室内器官和中枢交感调节系统内的产生途径中。我们的研究表明，低剂量输注ANG II会导致野生型雄性小鼠患高血压，但对完整的野生型雌性小鼠则不会。此外，我们已经证明，雄性小鼠中ANG II诱导的高血压可被中枢输注雄激素受体拮抗剂氟他胺以及中枢输注超氧化物歧化酶模拟物tempol所阻断。我们还发现，与雌性小鼠相比，长期输注ANG II后，雄性小鼠的脑室周器官神经元内活性氧水平更高。在雌性小鼠中，卵巢切除术、中枢性雌激素受体阻断或雌激素α受体完全敲除会增强ANG II的升压作用。最后，仅在雌性小鼠而非雄性小鼠中，中枢性一氧化氮合酶阻断会增加ANG II的升压作用。综上所述，这些结果表明性别差异以及雌激素和睾酮在ANG II诱导的高血压发展过程中起着重要作用。
