The CNS renin-angiotensin system

Abstract

The renin-angiotensin system (RAS) is one of the best-studied enzyme-neuropeptide systems in the brain and can serve as a model for the action of peptides on neuronal function in general. It is now well established that the brain has its own intrinsic RAS with all its components present in the central nervous system. The RAS generates a family of bioactive angiotensin peptides with variable biological and neurobiological activities. These include angiotensin-(1-8) [Ang II], angiotensin-(3-8) [Ang IV], and angiotensin-(1-7) [Ang-(1-7)]. These neuroactive forms of angiotensin act through specific receptors. Only Ang II acts through two different high-specific receptors, termed AT1 and AT2. Neuronal AT1 receptors mediate the stimulatory actions of Ang II on blood pressure, water and salt intake, and the secretion of vasopressin. In contrast, neuronal AT2 receptors have been implicated in the stimulation of apoptosis and as being antagonistic to AT1 receptors. Among the many potential effects mediated by stimulation of AT2 are neuronal regeneration after injury and the inhibition of pathological growth. Ang-(1-7) mediates its antihypertensive effects by stimulating the synthesis and release of vasodilator prostaglandins and nitric oxide and by potentiating the hypotensive effects of bradykinin. New data concerning the roles of Ang IV and Ang-(1-7) in cognition also support the existence of complex site-specific interactions between multiple angiotensins and multiple receptors in the mediation of important central functions of the RAS. Thus, the RAS of the brain is involved not only in the regulation of blood pressure, but also in the modulation of multiple additional functions in the brain, including processes of sensory information, learning, and memory, and the regulation of emotional responses.

Renin–angiotensin system in pain: Existing in a double life?

“…The components of the renin-angiotensin system (RAS) present in the central nervous system modulate sensory information, emotional and behavioral responses, stress, anxiety, learning and memory. 2,3 The angiotensin neuropeptides have been shown to impair the cognitive functions and, accordingly, angiotensin inhibitors improve learning and memory. [4][5][6] In contrast, studies from our laboratory and from others have described the learningfacilitating and memory-enhancing effects of angiotensin neuropeptides.…”

Decreased Expression of Angiotensin II Type 1 and Type 2 Receptors in the Brain After Long-Term Administration of Antihypertensive Drugs in Stroke-Prone Spontaneously Hypertensive Rat

“…The AT 1 is mainly expressed in blood vessels, heart, kidney, and adrenal and is also expressed in the brain (2,3). In the brain, the AT 1 is also expressed in microvessels (4), and the AT 2 is also expressed in neurons (5).…”

Cerebroprotective effects of RAS inhibitors: Beyond their cardio-renal actions

“…Consequently, further work on the brain RAS was carried out and led to elucidation of basic physiologies, including reabsorption and uptake of body fluid, blood pressure maintenance, and vasopressin release. 3 Angiotensin peptide, specifically angiotensin II (Ang II), induces cerebrovascular remodeling and promotes vascular inflammation and oxidative stress, resulting in dysregulation of cerebral blood flow (CBF). 4,5 Currently, this system has been implicated for its newly established effects, which are far beyond its cardio-renal effects, in several neurodegenerative disorders like Alzheimer's disease (AD), Parkinson's disease (PD), multiple sclerosis (MS, autoimmune demyelination), and bipolar disorder (BD) 6 .…”