Castration fails to prevent prenatally programmed hypertension in male rats

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.