Department of Pathology, Oregon Health & Science University, Portland, OR 97239-3098, USA.
Am J Physiol Regul Integr Comp Physiol. 2010 Apr;298(4):R1111-6. doi: 10.1152/ajpregu.00803.2009. Epub 2010 Jan 27.
Male offspring of rats that were modestly protein restricted during pregnancy become hypertensive as adults, whereas their female littermates remain normotensive. The purpose of this study was to determine the role of testosterone in promoting this sexual dimorphism of prenatally programmed hypertension. Rats were fed either a normal (19% protein, NP) or modestly protein-restricted (8.5% protein, LP) diet throughout pregnancy. Male offspring either remained intact or were castrated (CAS) at 30 days of age. Female offspring remained intact. At approximately 22 wk of age, the offspring were chronically instrumented for measurement of mean arterial pressure and renal function. Intact male LP offspring were hypertensive compared with male NP offspring (138 +/- 2 vs. 130 +/- 2 mmHg, P < 0.007), whereas female LP offspring were normotensive (123 +/- 1 vs. 122 +/- 2 mmHg in NP females). In CAS males, blood pressure in both diet groups was not different from that in intact males of the same group (138 +/- 3 mmHg in LP CAS males, and 131 +/- 2 mmHg in NP CAS males). Glomerular filtration rate and effective renal plasma flow were also not significantly affected by castration. However, castration significantly reduced protein excretion in LP males to levels not different from those in NP CAS and intact males. Renal histopathology scores showed a similar pattern. Thus removal of androgens by castration failed to provide any protective effect against the hypertension programmed by maternal protein restriction. Castration also failed to abolish the sex difference in blood pressure in both diet groups. These findings suggest that the lifelong presence of normal levels of testicular hormones does not play a major role either in maintaining baseline blood pressure higher in males than in females, or in promoting further elevations in blood pressure in males due to prenatal undernutrition. However, androgens such as testosterone may promote renal injury in LP males.
雄性子代大鼠在孕期接受适度蛋白质限制后会在成年期发展为高血压，而其雌性同窝仔则保持血压正常。本研究旨在确定睾酮在促进这种产前编程高血压的性别二态性中的作用。大鼠在整个孕期接受正常（19%蛋白质，NP）或适度蛋白质限制（8.5%蛋白质，LP）饮食。雄性后代在 30 天时要么保持完整，要么被去势（CAS）。雌性后代保持完整。大约在 22 周龄时，对后代进行慢性仪器测量以测量平均动脉压和肾功能。完整的雄性 LP 后代比雄性 NP 后代高血压（138 +/- 2 与 130 +/- 2 mmHg，P < 0.007），而雌性 LP 后代血压正常（NP 雌性中的 123 +/- 1 与 122 +/- 2 mmHg）。在 LP CAS 雄性中，两组饮食的血压与同一组的完整雄性没有区别（LP CAS 雄性中的 138 +/- 3 mmHg，以及 NP CAS 雄性中的 131 +/- 2 mmHg）。肾小球滤过率和有效肾血浆流量也不受去势的显著影响。然而，去势显著降低了 LP 雄性的蛋白质排泄，使其与 NP CAS 和完整雄性的水平没有差异。肾组织病理学评分也表现出类似的模式。因此，通过去势去除雄激素并不能提供任何保护作用来预防母体蛋白质限制编程的高血压。去势也未能消除两组饮食中血压的性别差异。这些发现表明，正常水平的睾丸激素的终生存在既不会在维持男性的基础血压高于女性方面发挥主要作用，也不会在由于产前营养不良导致男性血压进一步升高方面发挥主要作用。然而，睾酮等雄激素可能会促进 LP 雄性的肾脏损伤。
