Angiotensinergic neurons in sympathetic coeliac ganglia innervating rat and human mesenteric resistance blood vessels Jaspal Patil a , Eva Heiniger a , Thomas Schaffner b , Oliver Mühlemann a , Hans Imboden a, ⁎ a Institute of Cell Biology, University of Bern, Bern, Switzerland b Institute of Pathology, University of Bern, Bern, Switzerland Received 5 October 2007; received in revised form 8 January 2008; accepted 11 January 2008 Available online 18 January 2008 Abstract In contrast to the current belief that angiotensin II (Ang II) interacts with the sympathetic nervous system only as a circulating hormone, we document here the existence of endogenous Ang II in the neurons of rat and human sympathetic coeliac ganglia and their angiotensinergic innervation with mesenteric resistance blood vessels. Angiotensinogen - and angiotensin converting enzyme-mRNA were detected by using quantitative real time polymerase chain reaction in total RNA extracts of rat coeliac ganglia, while renin mRNA was untraceable. Cathepsin D, a protease responsible for cleavage beneath other substrates also angiotensinogen to angiotensin I, was successfully detected in rat coeliac ganglia indicating the possibility of existence of alternative pathways. Angiotensinogen mRNA was also detected by in situ hybridization in the cytoplasm of neurons of rat coeliac ganglia. Immunoreactivity for Ang II was demonstrated in rat and human coeliac ganglia as well as with mesenteric resistance blood vessels. By using confocal laser scanning microscopy we were able to demonstrate the presence of angiotensinergic synapses en passant along side of vascular smooth muscle cells. Our findings indicate that Ang II is synthesized inside the neurons of sympathetic coeliac ganglia and may act as an endogenous neurotransmitter locally with the mesenteric resistance blood vessels. © 2008 Elsevier B.V. All rights reserved. Keywords: RAS; Angiotensin II; SNS; Synapses en passant 1. Introduction Blood pressure control is predominantly regulated by the sympathetic nervous system (SNS) and the renin angiotensin system (RAS). The octapeptide angiotensin II (Ang II) is the effector component of the RAS and well known for his potent vasoconstriction action, which leads to increased blood pressure and release of aldosterone from the adrenal cortex. Local Ang II production at tissue level has been discussed in many different tissues [1,11–13]. Circulating Ang II in the blood has been reported to interact with the SNS at different sites and to directly stimulate the sympathetic activity [1,3,6,15]. Furthermore, it has been proposed that circulating Ang II functions at synaptic nerve endings for example with blood vessels by enhancing norepinephrine release and thereby facilitating sympathetic neurotransmission [1,4,5]. Controversially, it is also reported in some studies that Ang II has no or nearly negligible effect on the enhancement of neurotransmission at the postjunctional level [25,26]. Immunoreactive Ang II release and angiotensinogen mRNA expression in cardiac sympathetic ganglia has been studied [23]. The presence of RAS components in circulation and at tissue level has been reported [1], but the question of endogenous RAS in the neurons of sympathetic coeliac ganglia has not been addressed so far. We tested our hypothesis of an endogenous synthesis of Ang II in neurons of sympathetic coeliac ganglia and further their angiotensinergic innervation with mesenteric resistance blood vessels under normal physio- logical conditions, in normotensive rat and human tissues. Available online at www.sciencedirect.com Regulatory Peptides 147 (2008) 82 – 87 www.elsevier.com/locate/regpep ⁎ Corresponding author. University of Bern, Institute of Cell Biology, Baltzerstrasse 4, 3012 Bern, Switzerland. Tel.: +41 31 631 48 99; fax: +41 31 631 38 66. E-mail address: hans.imboden@izb.unibe.ch (H. Imboden). 0167-0115/$ - see front matter © 2008 Elsevier B.V. All rights reserved. doi:10.1016/j.regpep.2008.01.006