INVESTIGADORES
CHOI Marcelo Roberto
artículos
Título:
The renin angiotensin system in the central nervous system
Autor/es:
CHOI MR; CAVALLERO SC; FERNÁNDEZ BE
Revista:
Physiological Mini Reviews
Editorial:
Argentine Physiological Society
Referencias:
Lugar: La Plata; Año: 2011 vol. 5 p. 18 - 31
ISSN:
1669-5402
Resumen:
In addition to the renal renin-angiotensin system (RAS), which generates circulating Angiotensin II (ANG II), several local RAS exist in different tissues and organs, like the central nervous system (CNS), where all the components are found allowing ANG II generation. The brain RAS is not completely independent from the peripheral RAS, since ANGs generated at the periphery can interact with brain RAS at specific brain sites as the circumventricular organs (CVOs), which lack the blood-brain barrier and represent an interface between peripheral and central RAS. The CVOs, where ANG II and its receptors have been identified, are critically involved in the regulation of many homeostatic processes, including hydromineral balance, body temperature, and cardiovascular functions and hormone secretion control. In this way, brain RAS can exert paracrine, autocrine and intracrine functions, acting as a neurotransmitter in neurons of several brain areas. The endogenous brain RAS modulates the hypothalamic-pituitary-adrenal axis by means of synthesis and secretion of hypothalamic releasing factors control. ANGs produced in the CNS also stimulate endocrine secretions like arginine-vasopressin (AVP), oxytocin, corticotrophin-releasing hormone and adeno-corticotrophin (ACTH); and regulate blood pressure by increasing AVP and ACTH levels and modulating baroreceptor reflex and sympathetic output. Brain ANG II regulates also cardiovascular function and hydromineral balance through modulation of water and sodium intake by the stimulation of thirst, salt appetite and water excretion, enhancing many of ANG II peripheral effects. Brain RAS stimulates central autonomic sympathetic nervous activity, controlling central and peripheral sympathoadrenal systems and neuronal norepinephrine neurotransmission and, concomitantly, brain and body temperature. Brain ANG II also regulates serotonin transmission, by stimulating its neuronal synthesis and release. This action favour brain ANG II control on circandian rhythms. Central RAS may be also involved in the regulation of multiple additional functions in the brain, not completely established, including brain development, neuronal migration, processes of sensory information, cognition, learning, retention and memory, regulation of emotional responses, stress, sexual behaviour, apoptosis and cerebral blood flow. On the other hand, it has been established that the octapeptide ANG II is not the only active component of the RAS. New peptides were identified as metabolic products of ANG II, with similar or different functional properties. The heptapeptide ANG III (fragment 2-8) exhibits physiological and pharmacological effects similar to those of ANG II, which are mediated by their common receptors, AT1 and AT2. Different properties were demonstrated for the hexapeptide ANG IV (fragment 3-8) and for the heptapeptide fragment 1-7 (ANG 1-7), which are generated by tissue proteases and have specific receptors. These members of the ANG family are biologically active peptides formed in the CNS which play different roles in the brain as neurotransmitters, exciting neurons with high specificity; and as neuroendocrine, paracrine, autocrine and intracrine factors. Finally, other members like ANG fragments 3-7, 1-9 and 2-10 are relatively poorly known peptides and need further investigations to understand their physiological roles.