Castration Has Antihypertensive and Organoprotective Effects in Male but Not in Female Heterozygous Ren-2 Rats

Gender differences in the regulation of blood pressure (BP) and the contributions of the renin-angiotensin system remain controversial. We assessed the effect of castration on BP and organ damage, as well as angiotensin II (ANG II), estradiol and testosterone levels in heterozygous Ren-2 transgenic (TGR) rats and transgene-negative Hannover Sprague-Dawley control rats. Male TGR had severe hypertension throughout the experiment, while the BP of female TGR declined after 5 months to normotensive levels. Ovariectomy had no effect on BP, cardiac hypertrophy or proteinuria in female Ren-2 TGR. On the contrary, BP and cardiac hypertrophy were significantly reduced in castrated male TGR as compared to sham-operated TGR. Moreover, proteinuria in these animals was normalized to the levels of control rats. ANG II levels did not differ between male and female TGR, and no effect of castration on plasma and tissue ANG II levels was found either in male or female TGR at the end of the experiment. In conclusion, the contribution of the renin-angiotensin system to the gender difference in BP homeostasis seems to be negligible in aging heterozygous Ren-2 transgenic rats.