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.