[Frontiers in Bioscience 17, 2419-2432, June 1, 2012]

Angiotensinergic neurotransmission in the peripheral autonomic nervous system

Jurgen Bohlender1,2, Hans Imboden2

1Division of Angiology, Department of Internal Medicine, Centre Hospitalier Universitaire Vaudois, Lausanne, Switzerland, 2Institute of Cell Biology, University of Bern, Bern, Switzerland


1. Abstract
2. Introduction
3. Peptidergic neurotransmission
4. Angiotensin II as a neurotransmitter: evidence from the brain
5. Neuronal angiotensin II expression in the peripheral autonomic nervous system
5.1. Sympathetic postganglionic fibers
5.2. Sensory-afferent neurons in dorsal root and trigeminal ganglia
5.3. Evidence for renin-independent angiotensin II generation in peripheral ganglionic neurons
6. Angiotensin II in autonomic nervous fibers of the heart and intrinsic cardiac neurons
7. Potential therapeutic implications
8. Conclusion
9. References


Angiotensin (Ang) II has for long been identified as a neuropeptide located within neurons and pathways of the central nervous system involved in the control of thirst and cardio-vascular homeostasis. The presence of Ang II in ganglionic neurons of celiac, dorsal root, and trigeminal ganglia has only recently been described in humans and rats. Ang II-containing fibers were also found in the mesenteric artery and the heart together with intrinsic Ang II-containing cardiac neurons. Ganglionic neurons express angiotensinogen and co-localize it with Ang II. Its intraneuronal production as a neuropeptide appears to involve angiotensinogen processing enzymes other than renin. Immunocytochemical and gene expression data suggest that neuronal Ang II acts as a neuromodulatory peptide and co-transmitter in the peripheral autonomic and also sensory nervous system. Neuronal Ang II probably competes with humoral Ang II for effector cell activtation. Its functional role, however, still remains to be determined. Angiotensinergic neurotransmission in the autonomic nervous system is a potential new target for therapeutic interventions in many common diseases such as essential hypertension, heart failure, and cardiac arrhythmia.