Brain angiotensin II and synaptic transmission

The renin-angiotensin system is an enzymatic cascade by which angiotensinogen is cleaved by renin and then by angiotensin-converting enzyme to produce angiotensin II (Ang II) and subsequently other angiotensins. Biochemical and neurophysiological studies have documented the presence of the renin-angiotensin system and specific Ang II receptors in the brain. Also, circulating Ang II can exert some of its actions, such as blood pressure control and body fluid homeostasis, through stimulation of Ang II receptors in the circumventricular organs that lack a normal blood-brain barrier. In addition to some of the postsynaptic effects of Ang II, recent studies have revealed that Ang II regulates synaptic transmission in several brain regions, especially the nucleus of the solitary tract, hypothalamic paraventricular nucleus, and hippocampus. This review summarizes emerging new evidence on the effect of brain Ang II on glutamatergic and GABAergic synaptic transmission. This previously unrecognized presynaptic action of Ang II is important for the control of neuronal excitability and many physiological functions including autonomic control, hormone secretion, and memory. Future research on the role of brain-derived Ang II and its receptors in synaptic transmission will further enhance our understanding of the cellular mechanisms of Ang II and the relationship between the renin-angiotensin system and brain functions.