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J. Exp. Med.,
Volume 188, Number 4, August 17, 1998 661-670
By
§§
From the * Institute of Anatomy and the The renin-angiotensin system (RAS) has been traditionally linked to blood pressure and volume regulation mediated through the angiotensin II (ANG II) type 1 (AT1) receptor. Here we
report that ANG II via its ANG II type 2 (AT2) receptor promotes the axonal elongation of
postnatal rat retinal explants (postnatal day 11) and dorsal root ganglia neurons in vitro, and,
moreover, axonal regeneration of retinal ganglion cells after optic nerve crush in vivo. In retinal explants, ANG II (10 Institute of Pharmacology, Christian-Albrechts-University
Kiel, D-24105 Kiel, Germany; and the § German Institute for High Blood Pressure Research,
69120 Heidelberg, Germany
7-105 M) induced neurite elongation via its AT2 receptor, since the effects were mimicked by the AT2 receptor agonist CGP 42112 (105 M) and were entirely
abolished by costimulation with the AT2 receptor antagonist PD 123177 (105 M), but not by
the AT1 receptor antagonist losartan (105 M). To investigate whether ANG II is able to promote axonal regeneration in vivo, we performed optic nerve crush experiments in the adult rats. After ANG II treatment (0.6 nmol), an increased number of growth-associated protein
(GAP)-43-positive fibers was detected and the regenerating fibers regularly crossed the lesion
site (1.6 mm). Cotreatment with the AT2 receptor antagonist PD 123177 (6 nmol), but not
with the AT1 receptor antagonist losartan (6 nmol), completely abolished the ANG II-induced
axonal regeneration, providing for the first time direct evidence for receptor-specific neurotrophic action of ANG II in the central nervous system of adult mammals and revealing a
hitherto unknown function of the RAS.
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