Identification, Distribution, and Expression of Angiotensin II Receptors in the Normal Human Prostate and Benign Prostatic Hyperplasia

Abstract

The tissue distribution, cellular localization, and level of expression of angiotensin II (Ang II) receptors were examined in the normal human prostate and benign prostatic hyperplasia (BPH) by in vitro autoradiography, immunohistochemistry, and radioligand binding studies. In the normal human prostate, Ang II receptors were of the AT1 subtype and localized predominantly to periurethral stromal smooth muscle. The AT1 receptor antagonist losartan totally displaced specific[ 125I]-[Sar1,Ile8]Ang II binding, in a concentration-dependent manner, whereas the AT2 receptor antagonist PD123319 was without effect. There was no significant difference in receptor affinity, but AT1 receptor density was markedly reduced in BPH compared with that in normal prostate. In rat prostate, Ang II (0.01–1 μm) produced a concentration-dependent increase in[ 3H]-noradrenaline release from sympathetic nerves. The findings of the present study suggest that angiotensin AT1 receptors predominate in the human prostate. The high concentration of AT1 receptors in the periurethral region suggests a role for Ang II in modulating cell growth, smooth muscle tone, and possibly micturition. Furthermore, down-regulation of AT1 receptors in BPH may be due to receptor hyperstimulation by increased local levels of Ang II in BPH. Finally, Ang II may play a functional role in modulating sympathetic transmission in the prostate. These data support the novel concept that activation of the renin-angiotensin system may be involved in the pathophysiology of BPH.