Identification, distribution, and expression of angiotensin II receptors in the normal human prostate and benign prostatic hyperplasia

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. immuno histochemistry, and radioligand binding studies. In the normal human prosta te, Ang II receptors were of the AT(1) subtype and localized predominantly to periurethral stromal smooth muscle. The AT(1) receptor antagonist losart an totally displaced specific [I-125]-[Sar(1),Ile(8)]Ang II binding. in a c oncentration-dependent manner, whereas the AT(2) receptor antagonist PD1233 19 was without effect. There was no significant difference in receptor affi nity, but AT(1) receptor density was markedly reduced in BPH compared with that in normal prostate. In rat prostate, Ang II(0.01-1 muM produced a conc entration-dependent increase in [H-3]-noradrenaline release from sympatheti c nerves. The findings of the present study suggest that angiotensin AT(1) receptors predominate in the human prostate. The high concentration of AT(1 ) receptors in the periurethral region suggests a role for Ang II in modula ting cell growth, smooth muscle tone, and possibly micturition. Furthermore , downregulation of AT(1) receptors in BPH may be due to receptor hyperstim ulation by increased local levels of Ang II in BPH. Finally, Ang II may pla y a functional role in modulating sympathetic transmission in the prostate. These data support the novel concept that activation of the renin-angioten sin system may be involved in the pathophysiology of BPH.