Chen Y F, Naftilan A J, Oparil S
Department of Medicine, University of Alabama, Birmingham 35294.
Hypertension. 1992 May;19(5):456-63. doi: 10.1161/01.hyp.19.5.456.
Our previous studies demonstrated that the sexually dimorphic pattern of hypertension in the spontaneously hypertensive rat is androgen dependent. Gonadectomy retards the development of hypertension in young males, but not in females, and administration of testosterone propionate to gonadectomized spontaneously hypertensive rats of both sexes confers a male pattern of blood pressure development. The current study tested the hypothesis that renal and hepatic renin and angiotensinogen gene expression are also androgen dependent in the spontaneously hypertensive rat. Male and female spontaneously hypertensive rats underwent gonadectomy or a sham operation at 4 weeks of age. Subgroups of gonadectomized rats of both sexes were implanted with a 15-mm or 30-mm Silastic capsule filled with testosterone at the same time the gonadectomy was performed; a third group received an empty Silastic capsule. Northern and slot blot analyses were used to characterize and quantitate renin and angiotensinogen messenger RNA (mRNA) in the kidney and liver 18 weeks after the gonadectomy. Blood pressure, plasma renin activity, and hepatic angiotensinogen mRNA levels were higher in intact males than in females. Orchidectomy retarded the development of hypertension and lowered plasma renin and renal and hepatic angiotensinogen mRNA levels, and testosterone replacement restored the male pattern of hypertension and plasma renin and increased renal and hepatic angiotensinogen mRNA. Ovariectomy did not alter blood pressure or plasma renin but did lower renal renin and renal and hepatic angiotensinogen mRNA; testosterone increased blood pressure, plasma renin, renal renin and angiotensinogen mRNA, and hepatic angiotensinogen mRNA levels in ovariectomized females.(ABSTRACT TRUNCATED AT 250 WORDS)
我们之前的研究表明,自发性高血压大鼠中高血压的性别差异模式依赖于雄激素。去势会延缓年轻雄性大鼠高血压的发展,但对雌性大鼠无效,给两性去势的自发性高血压大鼠注射丙酸睾酮会赋予其男性血压发展模式。本研究检验了一个假设,即自发性高血压大鼠的肾和肝肾素及血管紧张素原基因表达也依赖于雄激素。雄性和雌性自发性高血压大鼠在4周龄时接受去势或假手术。在去势的同时,给两性去势大鼠的亚组植入装有睾酮的15毫米或30毫米硅橡胶胶囊;第三组接受空的硅橡胶胶囊。在去势18周后,使用Northern印迹和狭缝印迹分析来表征和定量肾和肝中肾素和血管紧张素原信使核糖核酸(mRNA)。完整雄性大鼠的血压、血浆肾素活性和肝血管紧张素原mRNA水平高于雌性。睾丸切除延缓了高血压的发展,降低了血浆肾素以及肾和肝血管紧张素原mRNA水平,而睾酮替代恢复了男性高血压模式和血浆肾素,并增加了肾和肝血管紧张素原mRNA。卵巢切除未改变血压或血浆肾素,但降低了肾肾素以及肾和肝血管紧张素原mRNA;睾酮增加了去卵巢雌性大鼠的血压、血浆肾素、肾肾素和血管紧张素原mRNA以及肝血管紧张素原mRNA水平。(摘要截短于250字)