Protective axis of the renin–angiotensin system in the brain

Abstract

The RAS (renin-angiotensin system) is composed of two arms: the pressor arm containing AngII (angiotensin II)/ACE (angiotensin-converting enzyme)/AT1Rs (AngII type 1 receptors), and the depressor arm represented by Ang-(1-7) [angiotensin-(1-7)]/ACE2/Mas receptors. All of the components of the RAS are present in the brain. Within the brain, Ang-(1-7) contributes to the regulation of BP (blood pressure) by acting at regions that control cardiovascular function such that, when Ang-(1-7) is injected into the nucleus of the solitary tract, caudal ventrolateral medulla, paraventricular nucleus or anterior hypothalamic area, a reduction in BP occurs; however, when injected into the rostral ventrolateral medulla, Ang-(1-7) stimulates an increase in BP. In contrast with AngII, Ang-(1-7) improves baroreflex sensitivity and has an inhibitory neuromodulatory role in hypothalamic noradrenergic neurotransmission. Ang-(1-7) not only exerts effects related to BP regulation, but also acts as a cerebroprotective component of the RAS by reducing cerebral infarct size and neuronal apoptosis. In the present review, we provide an overview of effects elicited by Ang-(1-7) in the brain, which suggest a potential role for Ang-(1-7) in controlling the central development of hypertension.

Heteromerization Between the Bradykinin B 2 Receptor and the Angiotensin-(1–7) Mas Receptor

“…1,2 It was surprising to find that Ang-(1–7) stimulation did not elicit Akt activation (present results). Despite that, constitutive Akt activation was present in MasR-transfected cells, suggesting that MasR activation is coupled to Akt activation despite the fact that Ang-(1–7) was absent.…”

Deficiency of angiotensin-converting enzyme 2 causes deterioration of cognitive function

“…11 Immunostaining for Ang-(1–7) has been observed in the areas of the brain, including the supra-optic and paraventricular nucleus (PVN) of the hypothalamus, neurons from the hypothalamus, and brainstem. 8 Furthermore, the level of Ang-(1–7) was detected from the hippocampus using high-performance liquid chromatography assay and increased during the acute and silent phases of pilocarpine-induced epilepsy. 12 Pereira et al 13 show that Ang-(1–7) is the main metabolite of Ang I in rat hippocampi.…”

“…8 ACE2 is widely expressed in brain areas involved in both the central regulation of blood pressure and cardiovascular function and disease, and the ACE2 level appears to be strongly regulated by other components of RAS. 11 Immunostaining for Ang-(1–7) has been observed in the areas of the brain, including the supra-optic and paraventricular nucleus (PVN) of the hypothalamus, neurons from the hypothalamus, and brainstem.…”

“…Moreover, the ACE2/Ang-(1–7)/Mas axis in the brain was also reported to have an important role in the regulation of blood pressure centrally and has an inhibitory neuromodulatory role in hypothalamic noradrenergic neurotransmission, and also acts as a cerebroprotective component by reducing neuronal apoptosis. 8 Xie et al 9 recently reported that Ang-(1–7) significantly alleviated chronic cerebral hypoperfusion-induced cognitive deficits in rats. However, in spite of these previous reports, the roles of the ACE2/Ang-(1–7)/Mas axis in cognitive function are largely unknown and remain to be elucidated in more detail.…”

Angiotensin-(1-7) attenuates hypertension and cardiac hypertrophy via modulation of nitric oxide and neurotransmitter levels in the paraventricular nucleus in salt-sensitive hypertensive rats

“…3 Previous peripheral experiments have shown that the actions of Ang-(1-7) mainly oppose the detrimental cardiovascular effects of angiotensin II, such as hypertension and cardiac hypertrophy. 4,5 Ang-(1-7) is widely distributed throughout the brain, including the PVN.…”