The renin-angiotensin system (RAS) is present in the human prostate and may be activated in benign prostatic hyperplasia (BPH), possibly contributing to the pathophysiology of this disorder by enhancing local sympathetic tone and cell growth. The functional role of the RAS in the prostate, however, is unknown. The present study was undertaken to determine whether angiotensin (Ang) II enhances sympathetic transmission in the prostate. The neuronal stores of the rat prostate were labelled with [(3)H]noradrenaline (NA). Ang II and Ang I enhanced [(3)H]NA release in a concentration-dependent manner. The Ang II receptor subtype 1 (AT(1) receptor) antagonist losartan and the AT(2) receptor antagonist PD123319 inhibited this facilitatory effect of Ang II and Ang I, whereas the other AT(2) receptor antagonist, CGP42112, was without effect. Bradykinin also increased [(3)H]NA release, which was inhibited by the B(2) receptor antagonist Hoe140. The angiotensin-converting enzyme inhibitor captopril inhibited the effect of Ang I, but potentiated that of bradykinin. Interestingly, captopril alone produced an increase in [(3)H]NA release which was inhibited by Hoe140. Losartan, but not PD123319 or CGP42112, inhibited [(125)I]-Ang II binding in Chinese hamster ovary cells transfected with the AT(1a) or AT(1b) receptor. In contrast, in cells expressing the AT(2) receptor, PD123319 and CGP42112, but not losartan, inhibited [(125)I]-Ang II binding. In conclusion, Ang II enhances the release of NA from sympathetic nerves of the rat prostate via a novel functional receptor distinct from the cloned AT(1a), AT(1b) or AT(2). These data provide direct evidence in support of a functional role for the local RAS in modulating sympathetic transmission in the prostate, which may have important implications for the pathophysiology of BPH.

This article has been cited by other articles:

				M. Byku, H. Macarthur, and T. C. Westfall Nerve stimulation induced overflow of neuropeptide Y and modulation by angiotensin II in spontaneously hypertensive rats Am J Physiol Heart Circ Physiol, November 1, 2008; 295(5): H2188 - H2197. [Abstract] [Full Text] [PDF]

				H. Uemura, H. Ishiguro, Y. Ishiguro, K. Hoshino, S. Takahashi, and Y. Kubota Angiotensin II Induces Oxidative Stress in Prostate Cancer Mol. Cancer Res., February 1, 2008; 6(2): 250 - 258. [Abstract] [Full Text] [PDF]

				I. Haulica, W. Bild, and D. N Serban Review: Angiotensin Peptides and their Pleiotropic Actions Journal of Renin-Angiotensin-Aldosterone System, September 1, 2005; 6(3): 121 - 131. [Abstract] [PDF]

				S. Guimaraes and H. Pinheiro Functional evidence that in the cardiovascular system AT1 angiotensin II receptors are AT1B prejunctionally and AT1A postjunctionally Cardiovasc Res, August 1, 2005; 67(2): 208 - 215. [Abstract] [Full Text] [PDF]

				O. A. O'Mahony, S. Barker, J. R. Puddefoot, and G. P. Vinson Synthesis and Secretion of Angiotensin II by the Prostate Gland in Vitro Endocrinology, January 1, 2005; 146(1): 392 - 398. [Abstract] [Full Text] [PDF]